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PLEASE ENABLE MAC ROS FOR SPELL CHECK! '
• PLEASE ENABLE MAC'ROS FOR SPELL CHECK! 8t. Cloud State University Office of Sponsored Programs NEW RESEARCHER AWARD FINAL REPORT Prepare and submit within one month of completion of grant Office of DATE: 6/26/2012 TO: Office of Sponsored Programs AS 210 FROM: Sarah Smits-Bandstra, CSD PROJECT: Peer-Reviewed Dissemination of Stuttering Research Date(s) of activity: December, 2011 - June 26, 2012 Amount Awarded: $4,000.00 Other funds used: $0 JUN 2 6 2012 Spon~ored Programs Source: What were the objectives of the project and to what extent have you been successful in achieving those objectives? The objective of this research award was to support my move toward peer-reviewed dissemination of my research. I conducted a research project comparing adults who stutter and adults with Parkinson's disease. I examined how each group learned new speech skills and collected their electrical brain activity while learning. This project has important implications for speech therapy for each of these patient populations. I have submitted two manuscripts based on this research to well-respected peer-review journals. I have successfully published peer-reviewed articles in both of these journals before (the Journal of Fluency Disorders, and the Journal of Clinical and Linguistic Phonetics). Both of the manuscripts I recently submitted were well received and I was encouraged to revise and resubmit them. During September and October, 20 II I was able to revise and resubmit my article entitled "Implicit sequence learning and retention on nonsense syllables in persons who stutter and persons with Parkinson's disease" to the Journal of Fluency Disorders. I received a reply in January rejecting the article (see decision letter attached), but suggesting a very promising alternative journal to which I should send a further resubmission. I researched several alternative journals to which I might send a resubmission, in particular the Journal of Movement Disorders and the Journal of Clinical Neurology. Between June 13 and June 26 th 2012 I revised my article again and plan to submit it to the Journal of Movement Disorders (see manuscript attached) before classes resume in August. Between June 4 and June 13 th I thoroughly re-analysed my data and rewrote my manuscript entitled "Early stage chunking of finger tapping sequences by persons who stutter and fluent speakers". The completed manuscript is attached. My co-author is on holidays until August. After he reviews the manuscript I intend to resubmit the article to the Journal of Clinical Linguistics and Phonetics before classes resume in August. A second objective of this research award was to support the mentorship ofa M.Sc. thesis student in the CSD department. This student is completing a thesis project analyzing the electrical brain activity data I .~ PLEASE ENABLE MACROS FOR SPELL CHECK! collected in my previous research studies. I needed support to travel with her to Montreal Quebec to the laboratory where I originally conducted my research . At McGill University there is a laboratory dedicated to the collection of electrical brain activity. I proposed to introduce this student (Whitney) to the process of collecting brain activity data within this laboratory setting. She would not otherwise have access to this advanced equipment at scsu. In May 2012 I accompanied my thesis student to Montreal, Quebec, Canada. We flew to Montreal and stayed at a hotel near the university (see attached Expedia receipt) and conducted our research on one pilot subject and four experimental subjects while we were there. We also participated as experimental subjects ourselves for two studies. My thesis student learned a great deal about recruiting subjects, running an experiment, and collecting brain waves using advanced equipment. This trip was an unqualified success and my student is analyzing the data we collected at this moment in order to incorporate it into her thesis. Discuss the outcomes and benefits of the project. Specifically comment on how the project has moved you towards the peer-reviewed dissemination of your work or the submission of a proposal for external funding. Include a copy of any published material, if applicable. Primarily, this project had great significance for my own professional development. At the end of this process, I will have published two first-author, peer-reviewed articles in respected journals. This project will also have significance for the CSD department, in particular, and SCSU, in general, because first author publications will improve my chances of success when applying to external agencies for research grants. Peer-reviewed publications will increase the visibility of SCSU within the field of communication disorders on an international level because of the international readership base of these journals. In addition, these publications will certainly impact student recruitment, particularly recruitment of high level students who wish to complete a thesis, apply for research scholarships, and perform research. This funding also allowed me to provide my thesis student with an experience in international research collaboration, and access to advanced technology, otherwise unavailable to her at SCSU. She plans to publish her research and present her results at the American Speech-Language Hearing Conference in November 2012. Gmail- Your Submission to the Journal of Auency Disorders hups:1 Imail.google.com/maill?ui=2&ik= 1892515e60&view=pt. .. Sarah Smits-Bandstra <[email protected]> Your Submission to the Journal of Fluency Di,sorders 2 messages Journal of Fluency Disorders <[email protected]> Wed, Jan 18, 2012 at 5:56 PM To: [email protected] Cc: [email protected] Ms. Ref. No.: JFD-D-11-00059 Title: Implicit Sequence Learning and Retention of Nonsense Syllables in Persons who Stutter and Persons with Parkinson's Disease Journal of Fluency Disorders Dear Sarah, Thank you for submitting your above-referenced manuscript to JFD, which has now been reviewed by an Associate Editor (AE) expert in the area, and two expert Editorial Consultants , who were blinded to your name and institutional affiliation, and by myself. While the reviewers and AE believe the paper has improved, there are still a number of problems with your paper, one being that the study does not provide a convincing argument. Therefore, and I know this will be disappointing, I regret to inform you that we have concluded that your manuscript is not acceptable for publication in the Journal. The review of the Associate Editor and those of the Editorial Consultants are enclosed. I hope that a careful reading of these enclosures will be helpful in understanding the basis for this publication decision and will assist you in developing future research projects or clinical stUdies and that you will continue to submit your work to the Journal of Fluency Disorders to consider for publication . Thank you for your submission to the Journal of Fluency Disorders. Yours sincerely, Professor Ashley Craig , PhD Editor Journal of Fluency Disorders Reviewers' comments: Dear authors, Your paper has been reviewed by two experts and myself. We agree that you have done a good job in trying to accommodate several concerns that were raised in previous reviews, but there remain some critical problems with this paper. Although the 1st reviewer indicates that he/she is willing to accept the changes, he/she also clearly expresses that the findings are not convincing. This sentiment is echoed by the comments of the 2nd reviewer, who also highlights several other issues that have to do with the quality of writing, in particular with respect to the discussion section. I agree with the assessment of the 2nd reviewer and the overall statement that the findings as reported in this manuscript are rather ambiguous in terms of the potential underlying sources for both the stuttering and Parkinson's individuals. This is reflected in the discussion, which offers little more than a somewhat disjointed collection of ideas and speculations that often have no direct 1 of 4 1/19/ 1212:47 PM ail - Your Submi ssion 10 the Journal of AueDey Disorders hups:l/mail.google.comimaill?u.i=2&ik=1892515e6O&view=pl. . relationship to the original data. Moreover, you frequently refer to assumed neuropathological issues in these populations without providing a proper evaluation of the actual processes that may have been involved In this particular experimental paradigm. In particular, this paper falls to address one of the main issues that was raised in previous reviews, namely how this specific type of task taps into speech motor processes in people who stutter or people with Parkinson's disease. Mhough you have tried to avoid this question by taking out a lot of references to speech motor control, you do highlight in the introduction and discussion problems in speech motor processes for both populations and the way therapy may not adequately address those, thus linking these issues to sequencing problems. However, you do not explain how the task that you used has any direct bearing on sequencing as relevant for speech motor control and the issues you raise regarding targets used in therapy. For example, how leaming to produce a gentle voice onset in stuttering therapy or loudness training for Parkinson has anything to do with identifying a pattern of nonsense syllable sequences remains totally obscure. It is also interesting to notice that the individuals who are supposed to be mostly affected by sequencing issues due to basal ganglia malfunction, viz. patients with Parkinson's disease , do not show the strongest difference with control data in reaction times between pairs of nonsense syllables that form part of the sequence vs. those that do not in the first session (and in the second session, all these trends are gone, which makes the findings even more puzzling). In conclusion, this paper addresses an important topic but the findings do not present a clear picture of what might be the underlying issues for either people who stutter or those who have Parkinson's disease. Furthermore , how the specific demands related to this particular paradigm tap into specific speech production problems for both populations remains unclear and the suggested links to neuropathology are highly speculative, especially for stuttering. Specific comments: 1. Given the large inter-subject variability, figures 2, 3, and 4 would be better presented in the form of box plots using msec as unit 2. On page 7, you refer to the study by Namasivayam & Van Ueshout (2008) but the information you provide is msleading. First, the 2nd session was separated by a week from the 1st session not just a few days and second, this was a study about implicit motor leaming in people who stutter (not explicit as you seem to suggest) . 3. Page 38, line 34: "ceiling effect'; you probably mean "flooring effect" . 4. The appendices can be reduced in size by removing A-D 5. Table 6 seems to show two outliers; one in the control group (a positive difference of 330 ms for subject 7) and one in the PWS group (a negative difference of 257 ms in subject 6). Ignoring that, overall, 2 controls, 7 PWS and 5 PPD show negative differences (i.e., faster RT for RAN vs. SEQ). Hardly strong evidence for general problems identifying sequences in the two patient populations. Reviewer #1 : The authors did a good job revising their manuscript according to the suggestions of myself, of the first reviewer, and of the AE. I still find the results not very convincing, but the interpretation of the outcome is now more adequate than before. I still have a few mnor points: p.3; 28 : "principles", not "principals" of 4 lf19112 12:47 PM Gmail • Your Submission to the Journal of Auency Disorders https:l/mail .goog1e.com!maill?u.i=2&ik=1892515e60&view=pt .. p. 3; 42-57 : Wikipedia should not be cited as a reference in a research article. The authors should rather refer to some acknowledged textbook of cognitive neuropsychology! p. 7 ; 10: remove comma p. 8; 43-46 : kappa coefficients still quoted as percentages, - see my comments to the earlier draft p. 11 ; 20: should probably read. (> 2SD from each group mean) . p. 17; 28: what is meant by". aberrant white matter physiology within the motor cortex ."? Within the cortex we only see grey matter, not white matter.? Please clarify! p. 19; 54: "preclude". not "precluding" Reviewer #2: This revised version is an improvement , having successfully addressed many of the complaints of this reviewer. The conceptual background is more coherent and the experimental design has greater clarity, helped by the schema given in Figure 1. The figures (please note subject-verb agreement error in the fifth level down) . As stated previously, this experiment addresses an interesting and important question about brain function in the two clinical groups under consideration . The background and rationale are stated clearly. (However, the use of a leng1hy paragraph from Wikipedia to define a phenomenon would be as unacceptable in a college paper and as it is in a scholarly article.) As an aside, acquiring a spatial shaping of an array of unrelated nonsense syllables is a long ways away from implicit learning as it occurs naturally. Some characteristics of orderly organization and/or an unfolding with transitional logic of SOME KIND inhere in anything we can think of as procedural memo'Y or procedural learning. Even though this is accepted practice in psychology studies, the problem of ecological validity remains. The authors should mention this limitation . (This limitation might contribute to the instability of the results.) Despite the several improvements, trouble arises again as the reader handles the overall managing of the study's results and interpretation. Just when the exposition seems to have an orderly direction, a derailment occurs in the form of a vagueness or contradiction . The abstrac1 states "the groups did not dilfer in retention of implicit learning." A problem with this statement arises from results for the retention session provided on page 12, where "PPD were significantly less accurate than PWS and near-significantly less accurate than controls." Even more perplexing, the authors state that the PPD group are weaker than other groups in implicit learning tasks. How does this general statement align with the claim that there was no observed defiCit in retention of implicit learning? The statement is consonant with results from the several studies reviewed in the introduction showing poor implicit leaming in PPD but the resu~s of this particular study are not. Or perhaps it has not been clearly explained for this reader. Part of the difficu~ may arise from the many statistical comparisons that were made and the inclusion of trends (p = .06) as meaningful to the interpretation of the study. The Inclusion of statistical trends in the interpretation may contribute to these conundra . While it is impressive to see the elfort that was undertaken for this study, the overall produc1 is lacking in coherence and interpretability and therefore does not contribute significantly to our understanding of the topic. The authors might consider limiting the report to partial components of the larger study that lend themselves to clarity in interpretation . It is inappropriate for this elaborate and complex study to claim to refer to "prelimina'Y" results (p . 19). Editorial comments: This paper is marred by numerous grammatical errors. "Howeve(' is used in several wrong ways (e.g., page 19, bottom). Commas are missing or introduced speciously (e .g ., page 19 top) . It was demorahzlng to thiS reviewer to see that a previous waming was NOT heeded in this revision: (reviewer's previous comment) Editorial: subjec1-verb agreement , top page; on p. 7, second paragraph, run-<ln sentence (however as coordinating conjunction) . 3 of 4 111911212:47 PM Gmail - Your Submission to the Journal of fluency Disorders https: llrnail.google.comlrnail/?ui=2&ik=1892515e60&view=pt. .. The authors are referred in a friendly manner to Strunk and White, Manual of Style . For further assistance, please visit our customer support site at http://supoort.elsevier.com. Here you can search for solutions on a range of topics, find answers to frequently asked questions and learn more about EES via interactive tutorials. You will also find our 2417 support contact details should you need any further assistance from one of our customer support representatives. Sarah Smits-Bandstra <[email protected]> Thu, Jan 19, 2012 at 9:21 AM To: Vincent Gracco <[email protected]> [Quoted text hidden) Sarah Smts-Bandstra, Ph.D. CCC-SLP Assistant Professor Department of Communication Sciences and Disorders (CSD) Brown Hall 103 St. Cloud State University 720 Fourth Ave S. St. Cloud , MN 56301 Dept: 320-308-2092 Office: 320-308-2018 Fax: 320-308-6441 Website: www.stcloudstate.edu/csd Email: [email protected] 40f4 1/19112 12:47 PM Running Head: SEQUENCE LEARNING AND RETENTION Verbal Implicit Sequence Learning and Retention in Stuttering and in Parkinson's Disease 2 Abstract BACKGROUND: This study investigated the functional integrity of implicit learning systems in persons with Parkinson's disease (PPD), persons who stutter (PWS) and control participants. METHODS: Participants completed a verbal serial reaction time task where they were required to say aloud four different syllables in response to four different visual stimuli. Unbeknownst to participants, the syllables fonned a repeating 8-item sequence. General learning was assessed by comparing groups' reaction time and accuracy over practice for Session One and after seven days on the Retention Session. Implicit sequence learning was assessed by comparing reaction time and accuracy for sequence syllables vs. random syllables on Session One and after seven days on the Retention Session. Questionnaires assessed participants' explicit sequence knowledge. RESULTS: PWS demonstrated delays but not deficiencies in general learning (significant) and retention (significant trend) relative to controls as measured by reaction time. PPD demonstrated less accuracy in general skill acquisition and retention relative to controls. Control participants demonstrated the expected pattern of implicit sequence learning in the initial session while PWS (significant), and perhaps PPD (significant trend) differed from this pattern. The groups did not differ in retention of implicit learning. All groups demonstrated similar limited explicit sequence knowledge on the questionnaires. CONCLUSIONS: PWS' differences in implicit sequence learning (involving the cortico-striato thalamo-corticalloop) may provide infonnation regarding possible etiological factors of stuttering. Results of the current study are sufficiently promising to embolden further research investigating implicit learning and retention in populations with motor speech disorders. Educational objectives: As a result of this activity the participant will be able to: (1) Differentially define procedural and implicit learning; (2) Summarize the reviewed literature concerning the perfonnance ofPPD and PWS on retention tasks over practice, and (3) Explain why a compromise in the functional integrity of the procedural learning system provides infonnation regarding possible etiological factors of stuttering. Keywords: Retention, Stuttering, Parkinson's disease, Nonsense Syllables, Serial Reaction Time (SRT), Sequence, Learning, Procedural Learning, Implicit Learning, Motor Learning, Practice, Basal Ganglia. Introduction Many programs designed for the treatment of various disorders of speech motor control (i.e. apraxia, dysarthria and stuttering 1) are based on the theoretical principles of motor learning. Duffy (2005) stated, "principles of motor learning should influence the structure of speech oriented treatment" (p. 449). Similarly Yorkston, Beukelman, Strand, and Hakel (2011) stated, "the clinician must address factors that facilitate motor learning" (p. 388). In the area of stuttering, Caruso and Max (J 997) held that a model of motor learning "may prove to be a valuable theoretical framework to interpret changes in stuttering" (p. 213). Most speech treatment programs are based on principles of motor learning derived from studies of non-speech skill learning in healthy populations. For example, Yorkston et al. (2011) reports "there is a large literature in cognitive motor learning that provides a good evidence base for our use in planning effective therapy for people with motor speech impairment" (p. 390). This reliance on non-speech literature is due to the unfortunate fact that the capabilities of persons with motor speech disorders for motor learning and retention, relative to persons without communication disorders, is relatively uninvestigated. Many of the strategies taught in speech therapy require conscious, cognitively-based skills (e.g., think LOUD) while other skills rely on unconscious, procedural learning skills that are difficult to verbalize (e.g., easy onsets). That is, most clinicians teach their clients what to do, as well as how to do it. The call of various authors to use motor learning principals intimates that, in addition to other aspects, clinicians should make the most of the procedural learning system. However, as mentioned above, there are few studies to date characterizing the integrity of the procedural learning system in persons with motor speech disorders. It is essential that research characterize the capabilities of various populations for procedural learning and retention. Only then can we proceed to manipulate learning variables for the purpose of improving procedural learning. The current study is a preliminary attempt to assess the integrity of procedural learning and retention in two different popUlations and as such, does not have direct implications for speech treatment. Definitions ofprocedural memory, implicit sequence learning, and serial reaction time According to Wikipedia (2011), Procedural memory is memory for how to do things. Procedural memory guides the processes we perform and most frequently resides below the level of conscious awareness. When needed, procedural memories are automatically retrieved and utilized for the execution of the integrated procedures involved in both cognitive and motor skills; from tying shoes to flying an airplane to reading. Procedural memories are accessed and used without the need for conscious control or attention. Procedural memory is a type of long-term memory and, more specifically, a type of implicit memory. Procedural memory is created through "procedural learning" or, repeating a complex activity over and over again until we figure out how to make all of the relevant neural systems work together to automatically produce the activity. Implicit procedural learning is essential to the development of any motor skill or cognitive activity. In this paper " learning" refers to consolidated learning (over four hundred trials, across two sessions, spanning approximately seven days). This investigation focused on learning that was procedurally based rather than declarative (recall and recognition skills), but may have had cognitive components. Implicit sequence learning is an example of procedural learning where participants learn to combine known movement components into a sequence but are unable to verbally describelidentify the sequence. Speech treatments involve both explicit and implicit learning. For example, therapists often model techniques such as easy onset, overarticulation, or slow rate and explicitly direct the patient whenlhow to move the vocal folds or articulators. After an initial model or explanation (explicit learning), the patient is left to 'figure it out' by trial and error over practice (implicit learning) how to further refine and consolidate the new skill. In contrast to explicit learning and direct procedural approaches, little is known about implicit learning in speech pathology . In the behavioral neuroscience literature, implicit sequence learning is acknowledged as a relatively independent functional brain system associated with specific structures and connections (particularly the basal ganglia and cortico-striato-thalamo-cortical connections) (see Doyon & Benali, 2005). Within the motor learning literature there exists a well-established protocol for examining implicit learning using serial reaction time tasks (Nissen & Bullemar, 1987) and verbal versions of serial reaction time tasks (Smith & McDowall, 2004; Westwater et at. 1998). The verbal serial reaction time task of the current study was chosen as a preliminary attempt to investigate implicit learning in patients with motor speech disorders. This task was utilized because extensive previous research in the area of motor learning has established high internal validity for this task. If it is determined that deficits in explicit and/or implicit motor learning and retention exist for certain populations, future research incorporating actual speech therapy tasks (high external validity) will be called for. Populations o/interest The current study examined the implicit sequence learning of persons with Parkinson's disease (PPD) and persons who stutter (PWS). PPD were recruited for the study because of the extensive body of research already existing regarding implicit sequence learning deficits for speech and nonspeech tasks in this population (see the following section). Previous serial reaction time studies with PPD were used as a guide for the methodology of the current study. PWS were chosen as part of the study because many researchers have proposed dysfunction within the cortico-striato-thalamo-cortical circuit as a possible etiological factor in stuttering. This hypothesis is based on comparisons of PPD and PWS in many areas including brain activity patterns during neuroimaging, sequencing performance, and speech symptoms (see Smits Bandstra & De Nil, 2007 for a review). Hypokinetic dysarthria is the primary speech symptom associated with PD. Nevertheless , repetitive speech phenomena such as disfluency is commonly observed (in up to 54% of advanced stage PD : Benke, Hohenstein, Poe we, & Butterworth, 2008), and can be a prominent or presenting symptom of some PPD (Koller, 1983). Several studies have observed fluctuations in stuttering dependent upon onset and progression of PD (Benke et aI., 2008), the use of dopaminergic medications (Brady, 1998), or stereotaxic surgery of sites within the cortico striato-thalamo-corticalloop (Burghaus et aI., 2006). Disfluencies most often associated with PD are stuttering, palilalia, speech freezing, and tachyphemia (see Louis, Winfield, fahn & Ford, 200 I for definitions and video-recorded examples). We also chose to examine the acquisition and retention of implicit sequence learning by PWS to characterized implicit learning and retention in this population. The ability of PWS to transition to automated performance (i.e. the procedural system) has been brought into question in previous research (Smits-Bandstra, De Nil, & Rochon, 2006; Smits-Bandstra & De Nil, 2009) and relapse is an acknowledged problem in this population (Blomgren et aI., 2005). If, in our unprecedented direct comparison, PWS and PPD demonstrated similar deficits on an implicit sequence-learning task known to involve the striatal circuit, this would provide information regarding possible etiological factors of stuttering. Moreover, consideration of the differences and similarities between stuttering and other motor control disorders such as PO is essential to stimulate new hypothesis-driven research to investigate the mechanisms of stuttering (Ludlow & Loucks, 2003). The role ofthe striatal system in implicit sequence learning In general, PPD demonstrate impaired implicit learning but relatively good explicit learning skills. In contrast, patients with intact striatal systems (e.g., Alzheimer's disease) have relatively good implicit learning but poor explicit learning, due to damage in the hippocampal region (Saint-Cyr et a!. , 1988). These "double dissociation" studies emphasize the importance of the striatal system relative to the hippocampal explicit learning system for implicit learning-type tasks (an example of an implicit learning task is the serial reaction time task described below). It should be emphasized, however, that these learning systems are not independent but interactive and that, in many cases of neurological disease, aspects of both types of learning can be affected to a certain extent. In addition, research has revealed roles for other areas of the brain (e.g., the cerebellum), in implicit motor learning, which should be acknowledged but will not be discussed in detail here (Sanes, Dimitrov, & Hallett, 1990). Serial reaction time tasks, whether manual or verbal, have reliably found poor implicit sequence learning in patients with impaired striatal systems such as Huntington ' s Disease (Saint Cyr et aI., 1988), and Parkinson's disease, unsurprising due to the striatal system deficits shared by these populations (see Siegert, Taylor, Weatherall, & Abernathy, 2006, for a meta-analysis). Impaired sequence acquisition by PPD has been found for both nonspeech and speech tasks. Schulz et a!. (200 l) measured the accuracy of articulatory patterns of PPD relative to control participants while learning a novel speech utterance (HThraim po /Ta mo dis" ) practiced SO times. They found only control participants demonstrated increased accuracy with reductions in duration and variability of productions over practice. Smith and McDowall (2004) conducted a serial reaction time task that required verbal responses to a 12-item sequence. Twenty Parkinson patients and 37 matched controls participated. Following a visual stimulus participants said aloud " A, B, C, or 0 " to indicate one of four spatial locations where the next anticipated stimulus would appear. Westwater and colleagues (1998) compared 13 non-demented PPD and II control participants on a similar verbal serial reaction time task with a 10-item sequence. Designating four locations on a computer screen as 1,2,3, and 4 /Tom left to right, PPD were required to say the number aloud as quickly and accurately as possible. For both studies PPD demonstrated less sequence specific learning relative to control participants as demonstrated by comparing the reaction times of sequence trials to the reaction times of random trials. Impaired acquisition of implicit sequencing has also been found in PPD both ON and OFF dopaminergic medication (Feigin et a!., 2003; Muslimovic, Post, Speelman, & Schmand, 2007). Muslimovic et a!. reported that the procedural learning impairment associated with PO is likely independent of cognitive dysfunction or dopaminergic medication. It is important to note that 6 both Feigin et al. and Muslimovic et al. indicated a mild negative effect of dopaminergic medication on declarative knowledge. Abbruzzese, Trompello and Marinelli (2009) concurred that the mechanisms of implicit learning appeared relatively independent from dopamine replacement therapy . While the characteristics of implicit sequence acquisition in PPD has been investigated by many studies to date, the retention of implicitly learned skills associated with striatal dysfunction (e.g., Parkinson's disease) is a new area of investigation. The role a/the striatal system in retention a/procedural skill Retention tests measure whether performance changes due to motor learning are well established. A retention test often consists of a sample of the practiced experimental task and may be conducted after one or several days (Guadagnoli, Leis, Van Gemmert, & Stelmach, 2002; Karni, 1996), or after a much longer rest period of months to years (Shadmehr & Brashers-Krog, 1997). Motor learning is not said to be well established, nor invulnerable to interference until after consolidation (Shadmehr & Brashers-Krog, 1997). Research indicates that consolidation occurs over a rest phase of five hours or longer (Brashers-Krog, Shadmehr, & Bizzi, 1996), after extensive practice (Hauptmann & Kami, 2002). A number of studies have investigated the importance of the striatal system for retention of implicit skills. Kawai, Kawamura, and Kawacru (1999) compared a patient diagnosed with Progressive Supranuclear Palsy (striatal involvement, poor implicit learning) and a patient diagnosed with Alzheimer' s disease (hippocampus involvement, poor explicit memory) using a bimanual coordinated tracing task . The patient with Progressive Supranuclear Palsy improved with training, but this improvement disappeared within a few months. The patient with Alzheimer's disease maintained improvements at the 18-month follow-up . This effect was confirmed with a larger patient sample by Mochizuki-Kawai, Kawamura, Hasegawa, Mochlwki, Oeda, Yamanaka, & Tagaya (2004). Retention of skills has also been found to be deficient as striatal degeneration continues, in later stages of Parkinson ' s disease (Doyon et al. 1998) and particularly for PPD with bradyk..inesia as the primary symptom (Vak..il & Herishanu-Naaman, 1998). Eight to 16 months after learning an implicit sequencing task, PPD who changed from Stage I to Stage 2 on the Hoehn and Yahr scale (1967) of the disease showed less retention of sequencing skill. The authors determined that the difference was not due merely to motor deterioration per se (Doyon et al. 1998). Of note, those studies which examined motor sequencing skills over one session or over a few days found good retention by PPD (Harrington , Haaland, Yeo, & Marder, 1990), while those whlch looked over months of practice found increasing differences in sk.ill retention between PPD and control participants (Agostino et aI., 2004). No studies to date have examined the retention of implicitleaming using a syllable serial reaction time task in populations with striatal disorders. Sequence Learning in PWS Similar to PPD, PWS have demonstrated some evidence of sequence learning differences relative to fluent speakers, however most experiments to date have focused on explicit sequence learning tasks only (see Smits-Bandstra & De Nil, 2007 for a review). Webster (1986) evaluated the ability of PWS and control participants to learn 4-element fmger tapping sequences and 7 found that PWS did not show improved accuracy after practice on sequences with no repeated elements (2-1-3-4 as opposed to 2-1-3-1) compared to controls. In a study by Smits-Bandstra, De Nil, and Saint-Cyr (2006) nine PWS and nine controls asked to type a IO-nwnber sequence (i.e. 14 2 1 3 1 2 4 1 3 4f). While the finger reaction times for the first trial were almost identical for both groups, PNS improved their reaction times more rapidly as compared to PWS. Ludlow, Siren, and Zikira (1997) asked PNS and PWS to practice two, 4-syllable nonsense words. Participants practiced recalling and producing the words between trials of a listening comprehension secondary task. Ludlow et al. (1997) found that PWS were impaired in their rate of learning as well as the overall accuracy of their nonsense word productions. Similarly, Cooper and Allen (1977) found that PWS required significantly more repetitions to demonstrate increased speed of repetition for read-aloud paragraphs and sentences compared to PNS when they used between 16 and 110 trial repetitions. In a study by Smits-Bandstra and De Nil (2009) 12 PWS and 12 control participants were presented visually with a 10-syllable sequence (Ita ba pa ta ga pa ga ta pa baf) on a computer screen and read aloud the sequence 30 consecutive times as quickly and accurately as possible. The results indicated that PNS demonstrated significantly more improvement on reaction time over practice compared to PWS. Retention/or PWS Smits-Bandstra, De Nil, and Saint-Cyr (2006) examined short-term retention of an explicit sequence learning task (participants were shown the whole sequence and encouraged to learn it). PWS demonstrated significantly slower reaction times for a ten-item nonsense syllable sequence relative to control participants on a retention test given approximately one hour after practice. Narnasivayam and van Lieshout (2008) measured the speed and coordination oflip movements ofPWS and control participants using electromagnetic articulography . PWS were asked to repeat the pronounceable nonsense words Ibapil, Ibipa/, Ibapiterl, and Ibipaterl for 12 seconds with a bite block in place. One to three days later, PWS demonstrated slower nonsense word performance and more variable lip coordination during production as compared to control participants. These preliminary studies suggest some deficits in explicit sequence learning and retention in PWS. However, the implicit sequence learning and retention capabilities of PWS have not been investigated. Purpose o/the current study The primary objective of the current study was to compare implicit sequence leaming and retention ofan implicit nonsense syllable sequence in PWS, PPD, and control participants. Similarities or differences between PPD and PWS will provide much needed clues as to the functional integrity of the implicit sequence leaming and retention system (Sciunidt & Wrisberg, 2004) in these populations. Functional deficits in implicit sequence learning, which involve the cortico-striato-thalamo-corticalloop, will provide information regarding possible etiological factors of stuttering. It has been suggested by several researchers in rehabilitative medicine that the knowledge of all aspects of motor learning abilities in patient populations is critical in designing more effective rehabilitative protocols (Abbruzzese et aI., 2009). Methodology Parlicipanls Participant infonnation is presented in Tables I and 2. Participants included 14 English speaking PPD (7 females; 65.1, SD 6.9). PPD were outpatients with idiopathic Parkinson's disease. Diagnosis by a licensed neurologist was based on the presence of a rigidity-akinesia syndrome, and responsiveness to Levodopa, without signs of pyramidal, cerebellar, or oculomotor deficits. PPDs' conversational speech was rated on overall intelligibility and dysarthria characteristics by a certified Speech-Language Pathologist (see Appendix A). The speech and reading samples of all PPD (14) scored below (2.8, SD 2.7) the very mild range (10-17) on the Stuttering Severity Instrument 4 (SSI-4; Riley, 2009). All PPD demonstrated less than 3% of syllables stuttered for their speech and reading samples. Table 2 also includes a rating of speech affectedness from the Activities of Daily Living subsection of the Unified Parkinson's Disease Rating Scale (Fahn, Elton, & Members of the UPDRS Development Committee, 1987), and overall stage of disease (modified Hoehn & Yahr, 1967; see Appendix B). Twelve PPD had intelligibility between 95-100%; and two PPD had intelligibility between 85-95%. A second rater, blind to the conditions of the study, also rated 20% ofPPDs' speech samples. Inter-rater reliability calculated using the kappa coefficient was 100% for intelligibility ratings, 84% for dysarthria characteristics, 94.7% for stuttering frequency of speech samples and 97.3 % for stuttering frequency of reading samples. All PPD were tested during the ON-cycle of their medication within 60-90 minutes of their last dose. Because dopaminergic treatment speeds up the execution of motor sequences (Benecke, Rothwell, Dick, Day, & Marsden, 1986), to minimize bradykinesia at baseline, we specifically studied medicated patients. Fourteen English-speaking PWS (6 females; 65.1, SD 5.7), scored in the very mild (9), mild (3) and moderate (2) range (10.3, SD 7.2) on the SSI-4 (Riley, 2009). All participants reported onset of stuttering in early childhood on the screening questionnaire. It is noteworthy that the large majority of PWS scored in the very mild to mild range on the SSI-4 . On average, PWS demonstrated an average of 3% of syllables stuttered (ranging from 1%- 15%). A second rater, blind to the conditions of the study, also rated 20% ofPWS' speech samples. Inter-rater reliability using the kappa coefficient was 94.8% for stuttering frequency of speech samples and 93.7% for stuttering frequency of the reading samples. Fourteen English-speaking participants (6 females; 65.0, SD 5.8) served as matched control participants. All PWS and PPD were screened for depression. All PPD were screened for mental state. All participants were screened for forward and backward digit span, hearing, vision, medication use (other than PPD medication), neurological and motor control difficulties (other than PD), and speech and language difficulties (other than those associated with PD or stuttering). PWS and PPD who had received speech therapy within the last 6 months were excluded as these treatments typically teach slowed rate of speech which may have interfered with the task . Written infonned consent was obtained and all participants were treated according to ethical treatment of human participant guidelines established by McGill University, the University of Toronto and the Baycrest Centre in Toronto. 9 Procedures Familiarization The experiment was composed of two sessions, Session One and the Retention Session. Before Session One, and again before the Retention Session, all participants underwent 16 training trials of the experiment. Participants saw four horizontal lines on the screen (see Figure I) and heard a beep. They were told that they should get ready and direct their attention to the screen when they heard this beep. Participants then saw an 'X' appear over one of the four lines and were told that each of the four 'X' locations was associated with a unique syllable. Participants were told that if an 'X' appeared in the top left comer, they must say "PA", in the top right comer, "PE", in the bottom left comer, "PI" and the bottom right comer, "PO". Participants were instructed to "Say the syllable aloud as quickly and accurately as possible as soon as the 'X' appears on the screen". In the first eight of the 16 training trials the correct syllable was written below the X when it appeared as a learning cue. The investigator provided spoken feedback regarding accuracy during all of the familiarization trials. The familiarization trials had no time limit so participants could take their time and ask questions. Verbal serial reaction time task Stimuli were presented on a IS-inch lap top screen with a viewing distance of 18-20 inches. For each single trial a blank screen was presented for 400 ms (from 0 ms to 400 ms) (see Figure I). Participants were presented with four horizontal lines (i.e.,::) in the middle of the screen for 900 ms (from 400 ms to 1300 ms). This visual cue was presented simultaneously with a 1000 Hz tone for 500 ms (from 400 ms to 900 ms). Finally an X over one of the four lines was presented for 2400 IDS (from 1300 to 3700 ms). Subjects had to respond immediately upon seeing the X by saying aloud the correct corresponding syllable they had leamed in training (e.g., "PA"). Each trial was followed by a jittered interstimulus interval of3600-3900 ms (from 3700 ms to between 7000 and 7300 ms). Jittered interstimulus intervals are variable time intervals inserted between consecutively presented individual stimuli to prevent anticipatory responses. Stimuli were presented using the Presentation 0.8 (Neurobehavioral Systems, 2004) software program. Unknown to the participants, the locations appeared in a predicable sequence of 8 locations (i.e. PO PI PO PE PI PA PE PA; see Appendix E). The participants were not made aware of the sequence pattern but were expected to leam it implicitly (unconsciously) as reflected in decreases in reaction time over practice. Thus it took 8 individual trials to complete the sequence. Nine sequences were contained in one "practice block". Each practice block ran through the eight-item sequence nine times (72 trials). There were short breaks every 2 or 3 sequences (short breaks of 5 s each). After each break the sequence trials began again, but always at a different point in the sequence to keep the sequential nature of the stimuli less obvious (implicit). During each break participants were given reminders of the correct syllable that went with each 'X' location. Session One The overall order of Session One is presented in Appendix E. No feedback regarding speed or accuracy was provided during Session One. The primary investigator corrected participants only if a participant incorrectly substituted one syllable for another for a whole block (e.g., PI for PO), indicating they had forgotten the training/instructions. After four blocks of 10 sequence practice (72 trials each), participants were presented with a fifth block. This fifth block is hereafter referred to as 'random' for expediency but was, technically, 72 pseudo-randomly generated locations (there were no repeated syllables). Retention Session The overall order of the Retention Session is presented in Appendix F. No feedback regarding speed or accuracy was provided during the Retention Session. The primary investigator corrected participants only if a participant incorrectly substituted one syllable for another for a whole block (e.g., PI for PO), indicating they had forgotten the traininglinstroctions. The Retention Session took place after approximately seven days for controls, (M = 6.7, SD = 3.1), PWS (M = 6.1, SD = 1.2), and PPD (M = 5.9, SD = 1.8), respectively. This length of retention period was selected because it was comparable to previous studies looking at retention after several days (Kawai et aI., 1999; Mochizuki-Kawai et aI. , 2004), but was still manageable for the investigator traveling considerable distances to various participants. Tbe Retention Session was composed of two blocks of sequence practice (72 trials each) followed by a third 'random' block of 72 pseudo-randomly generated locations. Explicit questionnaires and generate task Participants completed the " Day One" explicit awareness questionnaire after Session One and the "Day Two" questionnaire after the Retention Session (see Appendices C and D). The generate task was a computer task presented without pause following the ' random' block (block 3) in the Retention Session (see Appendix F). The generate task was identical to the experimental task described in the following paragraphs with one exception. The exception was, after a portion of each sequence had been completed (e.g., three trials), participants were presented visually with a "?" on the computer screen instead of the usual 'X' on one of four horizontal lines. When they saw the "?", participants were instrocted to "say the syllable corresponding to where they thought they 'X' would next appear." Dependent Variables and Statistical Analysis Excluded trials included yawns, sneezes, laughing, licking the lips, clearing the throat, equipment glitches, etc., and were not included in any of the analyses. In Session One control participants, PWS, and PPD had 7.9%, 7.4% and 7.4% excluded trials respectivel!. For the Retention Session control participants, PWS, and PPD had 4.8%, 2.7% and 2.9% excluded trials respectively. The dependent variables were accuracy of production and reaction time . Inaccuracy was defined as incorrect syllable substitutions (i.e. incorrect vowels; e.g. , !PAI for !PEl). PPD were in early stages of the disease with well-preserved speech skills (see Table 2). Dysarthria, voicing errors or distorted articulation of the initial /p/ consonant did not noticeably affect single syllable productions for these patients. All productions were categorized as correct productions or incorrect substitutions. An entire block was removed if there were three consecutive presentations or 4/5 presentations when the same incorrect syllable (e.g., PI) was always substituted in place of the correct syllable (e.g., PE), indicating the participant had forgotten the instructions/training. In these cases, participants typically made the error throughout the block. Participants received reminders of the syllable names and locations by tutorials on the computer screen during each II break, or by the investigator after a block of these recurring consistent errors were made. In Session One, control participants, PWS, and PPD had 15.4%, 12.3%, and 16.9% of blocks excluded as such, respectively. In the Retention Session control participants, PWS, and PPD bad 10.1 %, 8.9%, and 5.3% of blocks as excluded data, respectively. There were a considerable number of trials removed due to difficulty understanding to task. This is most likely the result of the minimal amount of training provided. In the current experiment minimal training was provided purposefully, in order to observe the early stages of the learning process. Disfluencies were defined as silent blocks or any repeated, prolonged, or e/Tortful sounds or syllables observed on-line, through videotape recordings and/or spectrogram analysis. Disfluencies were omitted from accuracy and reaction time analysis. For Session One, Control participants, PWS, and PPD bad 70, 109, and 187 of trials excluded as disfluent, respectively. In the Retention Session control participants, PWS and PPD bad 40, 60, and 82 of trials excluded as disfluent, respectively. Inordinately long reaction times were categorized as outliers (2+SD from each group mean) and were removed from analysis. One reason for the removal of these outliers was to control for akinesia/speech freezing in PPD. Video analysis confIrmed the presence of these effortless/tension-free speech hesitancies (no preparatory breath, no pre-forming of lips, no voicing or evidence of struggle) but the participant was still attending to the task. In Session One, outliers amounted to 4.6% for controls, 5.8% for PWS, and 4.2% for PPD. In the Retention Session outliers amounted to 3.2%, 3.0%, and 3.2% total trials for control participants, PWS, and PPD respectively. There were no cases of improbable/anticipatory reaction time in the data. The inclusion of a jittered interstimulus interval likely prevented such anticipatory responses. Syllable reaction time was measured as the time (ms) from the onset of the stimulus presentation to the voice onset of the syllable (the onset of the vowel after the initial consonant). Participant's speech was recorded using a dual channel digital audio tape recorder (Tascam DA 01) with 16 bit resolution and 48 kHz sampling rate. Reaction times were calculated off-line using waveform acoustic analysis Speech Analyzer 3.0.1 (SIL,2007). Reliability For Session One, percentage agreement with an independent rater on the occurrence of disfluencies vs. inaccuracies was 96.7%, and 99.9% respectively, based on 10% of the sequences. For the Retention Session, agreement was 97.2%, and 99.4% respectively, based on 10% of the sequences. An independent trained rater, blind to the conditions of the study, re-analyzed 10% of the participants' syllable reading acoustic waveforms. For Session One, occurrence agreement inter rater reliability for cursor placement within 10 ms was 98% (r = .99, ? = .98) and for the Retention Session, 93% (r = .99, r] = .98, a similarly high correlation). When, for example, rater one recorded reaction time for a syllable as 500 ms, if rater two recorded reaction time for tbe same syllables as 508 ms, they were considered in agreement within 10 ms. In both sessions there was 99.5% agreement within 20 ms. General learning (non-specific) vs. Implicit learning (5equence-specific) Generalleaming can be inferred from a gradual reduction in reaction time over practice blocks. Reaction times are a reflection of " generalleaming" because they are non-specific, 12 meaning they include some aspect of implicit sequence learning, but also more general task adjustment and stimulus-response learning ("PA" = lower left comer). Statistical analysis of reaction time included samples from the beginning of each block. Two means were taken from each practice block for a total of eight reaction time means across the four blocks. This was done to observe the large amount of change occurring during early trials as the sequence was being learned. The mean of trials 1-8 (a total of8 trials, the first total sequence) and the mean of trials 9-16 (a total of 8 trials, the second total sequence) were taken from Block I, Block 2, Block 3 and Block 4 in Session One. For the Retention Session, a traditional retention comparison was made between Session One Block 4 (the mean of trials 1-8) and the Retention Session Block I (the mean of trials 1-8). An additional, more detailed retention analysis included eight reaction time means across Session One and the Retention Session . There were four Session One means including trials 1-8 and 9-16 of Block I, and trials 1-8 and 9-16 of Block 4. There were four Retention Session means including trials 1-8 and 9-16 of Block I, and trials 1-8 and 9-16 of Block 2. This analysis over eight means (each an average of 8 trials) was chosen to compare the process of "forgetting" and "relearning" across groups in more detail. Poor retention was expected as a cubic curve where performance improves over practice in Session One but suffers upon introduction of the Retention Session. Sequence Blocks vs. Random Blocks Traditionally, implicit sequence learning is assessed by comparing reaction times of stimuli that follow a sequence pattern to the reaction times of random stimuli (Nissen & Bullemar, 1987). This comparison is made after some amount of practice so that participants have had time to implicitly learn the sequence. Reaction time for the random syllables should reflect several kinds of general learning (hence non-specific learning). Reaction time for the sequence syllables should be even shorter than reaction time for random syllables, reflecting implicit knowledge of the sequence (hence sequence-specific). Shorter reaction time for sequence vs. random syllables is interpreted as an indicator of implicit sequence learning. To assess implicit sequence learning in Session One we compared the reaction time of Block 4 sequence syllables (first 16 trials) with Block 5 random syllables (first 16 trials). To assess retention of implicit learning in the Retention Session we compared the reaction time of Block 2 sequence syllables (first 16 trials) with Block 3 random syllables (first 16 trials). This traditional comparison of a sequence block and a random block is problematic because within the random block, many of the syllables happened to fall into pairs, triplets, etc. that conformed to the practiced sequence. For example, the combination of a " PO" trial and a "PE" trial occurred in that particular order in the sequence (see Appendix E), but this exact combination also occurred sometimes when the syllable trials were randomly distributed. Recently researchers have proposed the use of probability as a more sensitive indicator of learned pair-wise associations or chunks within a sequence. Wilkinson and lahanshahi (2007) compared reaction times of frequently paired items (the practiced sequence items) to rarely paired items (sequence violations). SEQ vs. RAN Based on this more sensitive, probability-based analyses , the 'random' block (Block 5) trials were divided into syllable pairs that conformed to the sequence (SEQ), or violated the sequence (RAN). That is, within the random block, trial pairs that occurred in the sequence (e.g, PO PEl, 13 and were practiced in that order hundreds of times were called SEQ. Within the random block, pairs of trials that never occurred in the sequence (e.g., PE PO) and were never encountered before by the participant were called RAN (see Appendix E). Wilkinson and Jahanshahi (2007) demonstrated that the reaction time of the second syllable in each SEQ pair captured the 'anticipation' associated with implicit learning. This shortened 'anticipatory' reaction time occurred because subjects who implicitly knew the sequence could anticipate which syllable followed another. Within Session One, the first 16 RAN trials and the first 16 SEQ trials of the random block (Block 5) were included in analysis (see Appendix E). Within the Retention Session, the first 16 RAN trials and the first 16 SEQ trials of the random block (Block 3) were included in analysis (see Appendix F). Explicit questionnaires and generate task Some degree of explicit knowledge of a sequence/pattern of stimuli often arises during a serial reaction time experiment and the greater the extent of explicit knowledge, the bener sequencing performance (Mayr, 1996). Therefore, it is incumbent upon researchers to measure explicit knowledge as a potential confound of sequence learning that is assumed to be predominantly implicit. Traditionally, researchers have employed an explicit questionnaire where parts of the sequence are presented for participants to recognize/identify (Eimer, Goschke, Schlaghecken, & Sturmer, 1996; Ghilardi et aI., 2007; Russel & Rosier, 2000). We presented two-, three-, and four-syllable portions of the sequence as suggested by Russel and Rosier (2000) so as not to underestimate explicit knowledge of parts of the sequence, even if participants had not realized the whole sequence. We included the explicit questionnaire score as a dependent variable reflecting the extent to which sequencing performance can be accounted for by explicit rather than implicit knowledge. For the Day One questionnaire (see Appendix C), participants were awarded single points for each portion of the sequence they correctly identified as occurring "always" or "often" in the experiment. Additional single points were awarded for violations of the sequence they correctly identified as "rarely" or "never" occurring in the experiment. Ten total points were possible with two correct answers and three foils (chance performance = 40%). For the Day Two questionnaire (see Appendix D), participants were awarded single points for each portion of the sequence they correctly "guessed", "were somewhat sure", or "were sure" were part of the sequence. Additional single points were awarded for violations of the sequence they correctly "guessed", "were somewhat sure", or "were sure" were NOT part of the sequence. Ten total points were possible with three correct answers and three foils (chance performance = 50%). Scores greater than chance (40% for Day One and 50% for Day Two) indicated increasing explicit knowledge of the sequence. Questionnaire scores were expected to approach chance levels indicating predominantly implicit learning of the sequence. Recently there has been some evidence that questionnaires may underestimate explicit knowledge (Pe igneux et aI., 2000), because they are completed sometime after the actual experiment and are presented in a different media than the sequence (paper and pen vs. computer screen and keyboard). In response to these concerns we also included a computer-based "generate" task (see Appendix F; see also "explicit questionnaires and generate task" in the method section). Following the Retention Session participants completed the generate task. The generate task was very similar to the experimental task. Stimuli were presented on the computer and participants responded by saying the correct syllables aloud . Participants were awarded a 14 point for each correct guess regarding which syllable carne next in the sequence. The generate score was out of ten possible points with one correct answer and two foils (chance performance = 33%i. Generate scores were expected to approach chance levels. Results Accuracy Analysis was completed using 3866 trials (54 blocks) for controls, 4047 trials (56 blocks) for PWS and 3815 trials (53 blocks) for PPD in Session One. For Session One a 3 (Group) x 4 (Block 1 - 4) ANOVA revealed a significant Group main effect for accuracy, F (2,37) = 4.0,p <. 01, ,:,1 = .22. No other significant effects were found. A between-groups Least Significant Difference (LSD) post hoc test revealed PPDs' accuracy rate of 95.6% (0.9) across blocks was significantly lower than that of control participants, 97.5% (0.4) and PWS', 98 .0% (0.7), as shown in Figure 2. Analysis was completed using 2392 trials (33 blocks) for controls, 2547 trials (35 blocks) for PWS and 2451 trials (34 blocks) for PPD in the Retention Session. For the Retention Session a 3 (Group) x 4 (Block 1 - 4) ANOVA revealed a significant Group main effect for accuracy, F (2,32) = 4.4,p = .02, ,:,1= .22. A between-groups LSD post hoc comparison indicated PPD were significantly less accurate than PWS and near-significantly less accurate than controls (p = .06) across blocks. A significant Block main effect was also found, F (2,32) = 15.9, p = .00, ,:,1= .33, indicating better accuracy over practice during the Retention Session. No other significant effects were found. Two 3 (Group) x 2 (Condition: Ran vs. SEQ) ANOVAs revealed no significant differences for Session One or the Retention Session. Reaction time for general (non-specific) skill learning For both Session One and the Retention Session, a log transformation was made of the reaction time data and the Greenhouse-Geisser correction was made for all comparisons. Analysis was completed using 864 trials for controls, 868 trials for PWS and 865 trials for PPD in Session One. For Session One a 3 (Group) x 8 (Block; 8 means across practice blocks) ANOVA revealed a significant Block main effect for reaction time, F (7,37) = 33.2,p = .00, ,:,1 = .47. Reaction times decreased over practice blocks (see Tables 3, 4, and 5 in Appendix G). A significant Group x Block interaction was also found , F (14,37) = 4.8,p = .01,':' = 21 (see post hoc below). No other significant effects were found . Three 2 (Group) x 8 (Block) post-hoc ANOVAs (contrasting the reaction time ofPPD vs. controls, PWS vs. PPD, and PWS vs. controls over practice blocks) revealed that the reaction times of control participants improved more quickJy after practice relative to PWS, F (I, 25) = 11.2, p =. 00, ,:,1 = .31. No other significant effects were found. Analysis was completed using 416 trials for controls, 416 trials for PWS and 427 trials for PPD in the Retention Session. For the Retention Session complete data were only available for 12 PWS, 12 PPD and 13 control participants. A 3 (Group) x 2 (Session One, Block 4 vs. Retention Session, Block 1) ANOVA found no significant differences. Figure 3 depicts a more detailed analysis for retention described under the "general learning vs . implicit learning" heading in the Dependent Variables section. A 3 (Group) x 8 (Block) ANOVA revealed a significant Block main effect for reaction time, F (7,34) = 12.5, p = .00, ,:,1 = .27. Reaction 15 times decreased significantly over blocks. A near-significant Group x Practice interaction was also found, F (14, 34) = 2,7, P = .08, ~2 = .14, indicating PWS showed slower reaction times on the first practice block of the Retention Session relative to the other groups" No other significant effects were found. Reaction lime for implicit (sequence-specific) learning Analyses were designed to assess learning of the entire sequence (Sequence Blocks vs. Random Blocks) and learning of the pair-wise associations or chunks within the sequence (SEQ vs. RAN; Wilkinson & Jahanshahi, 2007). Sequence Blocks vs. Random Blocks Analysis was completed using 431 trials for controls, 433 trials for PWS and 431 trials for PPD in Session One. For Session One a 3 (Group) x 2 (Condition) ANOVA compared the groups' log-transformed reaction time on Block 4 (sequence) vs. Block 5 (random). Complete data sets were obtained from 14 control participants, 13 PWS and 14 PPD. A significant Condition main effect was found, F(I , 38) = 23.5 ,p = .00, ~2 = .38. Block 5 reaction times were slower than Block 4 reaction times. No other significant effects were found , Analysis was completed using 400 trials for controls, 413 trials for PWS and 420 trials for PPD in the Retention Session. For the Retention Session a 3 x 2 ANOVA compared the groups' mean reaction time for Block 2 (sequence) vs, Block 3 (random). A significant Condition main effect was found, F (I, 38) = 4. 1, p = .05, ~2 = .10. Block 3 reaction times were slower than Block 2 reaction times. No other significant effects were found. SEQvs. RAN Analysis was completed using 427 trials for controls, 421 trials for PWS and 427 trials for PPD in Session One. For Session One a 3 (Group) x 2 (Condition: SEQ vs. RAN) ANOVA assessed the groups' log transformed reaction time for SEQ vs. RAN pairs. A significant Condition main effect, F (1,39) = 9.0,p = .01 , ~2 = .19, and a significant Condition x Group interaction was found, F (2 , 39) = 3.8, p = .03, ~ 2 = .17. RAN reaction times were slower than SEQ reaction times. Three 2 (Group) x 2 (Condition) post hoc ANOVAs confirmed a significant Condition x Group interaction for PWS vs. control participants, F (I, 26) = 7.3, P = .0 I, ~2 = .22, and a similar near-significant trend for PPD vs. control participants, F (1,26) = 3.2, p = .08, ~2 = .11 (see Figure 4). Control participants had much faster SEQ vs. RAN reaction times relative to the other groups. No other significant effects were found (see Table 6 in Appendix G). Analysis was completed using 388 trials for controls, 411 trials for PWS and 395 trials for PPD in the Retention Session. On tbe Retention session a Condition main effect, F (I, 36) = 25.0,p = .00, ~2 = .46, was the only significant finding (see Table 7 in Appendix G). RAN reaction times were slower than SEQ reaction times. Explicit questionnaires and generate task Control participants, PWS, and PPD scored 3.1 (2.1),3.4 (\.8), and 3.2 (\.8) out of 10, respectively on the Day One questionnaire. Participant groups' scores did not significantly differ, and all groups performed near chance levels (see previous section). Control participants, PWS, and PPD scored 4.3 (2.1), 5.1 (1.4 ), and 5.2 (1.3) out of 10, respectively on the Day Two questionnaire. Participant groups' scores did not significantly differ, and all groups performed 16 near chance levels. Control participants, PWS, and PPD score 3.7 (1.5), 3.6 (1.4), and 3.4 (\.7) out of9 respectively for the generate task. Groups' scores did not significantly differ and all groups perfonned near chance levels. Discussion Accuracy In agreement with previous research (Wilkinson & Jahanshahi, 2007), PPD demonstrated significantly poorer accuracy in general (non-specific) learning over practice in Session One and in the Retention Session. It is important to note, however that, while statistically significant, all groups perfonned with high levels of accuracy. PPD's accuracy levels were only a few percentage points less than the other groups. Based on a comparison of PPD and control participants on a sequence learning study, Dominey et a1. (1997) concluded that PPDs' implicit learning appeared relatively intact only when knowledge of results is present to guide learning. In concordance, Guadagnoli, Leis, Van Gemmer!, and Stelmack (2002) reported Parkinson patients required 100% knowledge of results (relative to 20% for control participants) in order to demonstrate commensurate retention of a simple timing movement. In the present study, we did not manipulate "feedback" as an independent variable, which likely explains the reduction in accuracy. Reaction time for general (non-specific) learning Reaction time and accuracy differences over practice represented general (non-specific) learning (Smith & McDowall, 2004 ; Westwater et aI., 1998). While the figures in this paper display group means for reaction time, it is important to point out that there was individual variability within each group and considerable overlap between groups (see Appendix G). All groups showed significant general learning, achieving a mean reaction time of approximately 900 ms by Block 4 in Session One and by Block 2 in the Retention Session. This result suggested that PPD and PWS were not "slower overall". Our choice of early stage, medicated PPD, appears to have been successful in minimizing akinesialbradykinesia effects for motor execution of the sequence. Our results indicated poorer accuracy for PPD (see Wilkinson & Jahanshahi, 2007) instead of slower reaction times found in other studies (Smith & McDowall, 2004; Westwater et aI., 1998). This difference may have arisen due to our diligence in identifying and removing disfluencies and outliers (akinetic speech freezing) from the reaction time data. PPD had more than twice as many disfluencies relative to control participants and a great deal more than PWS (see the dependent variables section). Our finding of a high number of disfluencies in the data agrees with previous findings of high rates of disfluency for PPD as previously reported (Benke et aI., 2008). This difference may also have arisen due to a difference in difficulty level. Our learning task required participants to learn an arbitrary stimulus/response association between a spatial location and a nonsense syllable while previous studies required participants to name presented letters or numbers appearing in different spatial locations (e.g., "A" or "4"). It is important to empbasize that the current study used only early stage, non demented PPD and this is in contrast to other studies in the literature. This may have been an important factor explaining this discrepancy with the existing literature. PWS' difficulties were limited to reaction time differences in early trials in Session One, which may be attributable to difficulty with acquisition of set. While PWS had a ' slow start', 17 they were not slower overall and demonstrated good nonspecific learning (a large improvement in reaction time) during Blocks 2, 3 and 4 so that their reaction times became equivalent to those of controls. This "slow start" was also noted for PWS during sequence learning tasks in two previous studies (Smits-Bandstra, De Nil, & Saint-Cyr, 2006; Smits-Bandstra & De Nil, 2009) and on a review of PWS' performance on reaction time studies in general (Smits-Bandstra, 20 I 0). During early trials it has been hypothesized that participants use compiled sensory information to guide recognition and facilitation of appropriate preexisting learned movement patterns (synergies) while inhibiting irrelevant ones (Saint-Cyr, 2003). The critical role of the cortico-striato-thalamo-cortical circuit for this process is well established within the neuroscience literature (Grafton, Hazeltine, & Ivry, 2002; Carbon & Eidelberg, 2006), as is PPDs' difficulty with acquisition of set (Saint-Cyr, 2003). Peigneux and colleagues (2000) suggested that the striatum "plays a significant role in the selection of the most appropriate responses in the context created by both the current and previous stimuli" (p. 179). Most interesting to note was PWS' recurring 'slow starts' on the Retention Session. 4 Based on an exploratory post-hoc analysis • results indicate there are reaction time differences on these Retention Session early trials with some PWS not responding as quickly as participants in other groups. One speCUlative explanation for this difficulty with acquisition of set is that the sensory context and/or movement patterns for the syllables were not easily accessible/identifiable for selection and facilitation by the cortico-striato-thalarno-cortical circuit due to aberrant white matter physiology within the motor cortex found in previous studies (Beal, Gracco, Lafaille, & De Nil, 2007; Foundas, Bollich, Corey, Hurley, & Heilman, 2001; Sommer, Koch, Paulus, Weiller, Buchel, 2002). The results of the current study may partially explain why PWS do so well in the therapy room but struggle when attempting to re-access learned patterns in transfer situations or in the long term. Clearly further research is needed in this area, as an important limitation of the current study is the lack of generalization from our visual , nonsense syllable task to conversation speech or typical speech skills taught in speech therapy. Reaction time for implicit (sequence-specific) learning Sequence Blocks vs. Random Blocks For Session One, reaction time slowing was observed for all groups upon introduction of the random trials in Block 5 and for the Retention Session, upon introduction of the random trials in Block 3. These findings indicated recognition of the implicit sequence in both Session One and the Retention Session for all the groups. In contrast to previous studies PPD and control participants did not differ on these sequence block vs. random block, sequence-specific contrasts (Smith & McDowall, 2004; Westwater et al. 1998). It should be noted that differences in reaction time between sequence blocks and random blocks were typically only 40 ms smaller for PPD relative to controls in previous studies, a small difference. In the current study existing smaU group differences may have been masked because this paradigm had a reduced total number of practice trials relative to previous studies. In addition, group differences may not have reached statistical significance because the current study recruited early-stage, mildly affected PPD relative to other studies. As an alternative interpretation it must be considered that the syllable task in the Current study may not have been as heavily reliant on implicit memory as previous tasks. Speech, more than other movements, likely involves a complex interaction of implicit and explicit systems. This may explain, in part, 18 why speech movements are relatively preserved in many PPD relative to other movements and why speech problems are relatively resistant to dopaminergic treatments. SEQvs. RAN For both Session One and the Retention Session, SEQ reaction times were significantly faster than RAN reaction times indicating that our experimental manipulation was successful in eliciting implicit learning (Nissen & Bullemar, 1987). As expected, control participants demonstrated faster reaction times for SEQ vs. RAN syllable pairs relative to PWS (significant difference) and PPD (non-significant trend) in Session One. This finding was interpreted as more efTective implicit sequence learning by controls relative to the other groups over practice. PPD showed the expected pattern of slower reaction times on implicit (sequence-specific) learning tasks relative to controls found in previous studies (Smith & McDowall, 2004; Westwater et aI., 1998). However this difference was limited to a non-significant trend. Surprisingly, as a group, PWS' pattern of implicit learning differed significantly from controls (see Figure 4). One postulation is that PWS used excellent explicit and/or general learning skills to compensate for "slow starts", and either effectively compensated for implicit learning deficits or did not demonstrate deficits in implicit learning at all. The current study was successful in assessing implicit learning to some degree but was limited in that there was no opportunity to observe changes in performance as explicit knowledge developed nor was there an opportunity to contrast implicit vs. explicit knowledge of the same task (e.g., having some groups know about the sequence while other groups do not). Groups did not difTer in implicit learning on the Retention Session suggesting PWS and PPD had good retention of implicitly learned skills. This finding is in agreement with comparable studies with PPD that examined retention over several days and found minimal or no impairment in retention (Harrington et aI. , 1990). Alternatively, this result may have been attributable to a ceiling efTect. Controls attained reaction times of approximately 900 ms in Session One and no group attained reaction times faster than 900 ms subsequently for the pseudo-random blocks. Explicit questionnaires and generate task It has been shown that greater explicit/declarative knowledge is associated with better performance in healthy participants (Mayr, 1996), although not for PPD (Boyd & Winstein, 2006). No groups showed explicit knowledge for Session One or the Retention Session, indicating better sequencing performance by any group was not likely due to a greater degree of explicit knowledge . It has been argued that recall tests after the fact do not accurately reflect true explicit knowledge (Russeler & Rosier, 2000) therefore we included the generate task (similar to that used by Peigneux et aI., 2000). For both Session One and the Retention Session, generate scores were equivalent to chance and did not differ from questionnaire scores. Theoretical implications Several studies have been conducted to investigate the neural correlates of intensive training of speech " loudness" training in the LSVT program (Fox, Ramig, Ciucci, Sapir, McFarland, & Farley, 2006; Narayana et aI., 2010). These studies seem to suggest that while treatment is effective in changing behavior, the training required to institute such a change is 19 intensive, supplemented by many types of feedback and frequent knowledge of results, and is not accompanied by the expected neural changes in the primary motor and sensory cortices (Karni et aI., 1998). Instead, these studies report increased neural activity in areas associated with " top down" (explicit) attention and monitoring, suggesting compensation and/or explicit strategy use rather than implicit learning per se (Fox et aI., 2006; Narayana et aI., 2010). This emphasis on monitoring may have evolved as a response to difficulties patients have transitioning to implicit learning as well as retaining proficiency for new speech patterns. As defined in the introduction, implicit learning, once established is relatively automatic and feed fOIWard (not reliant upon feedback). Several researchers have presented evidence ofPPOs' (Dominey et aI., 1997; Fattapposta et aI., 2002) and PWS' (Civier, Tasko, & Guenther, in press; Max, 2004) difficulty with feed fOIWard motor control. Results of the current study provide preliminary support for differences, but not necessarily deficits, in the use of feed fOIWard or implicit learning by PWS and PPO. 11 can not be discounted that, for both PPO and PWS, the stability of the system on any given day may detennine how welileamed sequences can be expressed as long sequences planned in advance of the movement (Smiley-Oyen, Lowry & Kerr, 2007). Implicit learning and feed fOIWard control may, in fact, be intact, but are only incompletely or sporadically expressed due to instability of the motor planning/execution systems. This tentative proposal requires further investigation. 11 must also be mentioned that sequential learning by PWS or PPO might have been affected by differences in the focus of attention, especially in tbe beginning of the test. If attention and cognitive processing resources required for implicit sequence learning are diverted for speech motor execution, reduced implicit sequence learning results. Both PPO and PWS have demonstrated difficulties in the face of dual task demands (see Smits-Bandstra & Oe Nil, 2007 for a review) indicating a need for further study of the effects of attention in this area. Conclusion The purpose of this study was to compare the functional integrity of procedural learning and implicit memory systems in PPO, PWS, and control participants. In agreement with previous studies, the current preliminary results suggest there are differences with some PPO doing not as well as individuals in other groups on the implicit (sequence-specific) learning tasks used in the current study (non-significant trend). Although requiring replication, the current study suggests PPO did not demonstrate a retention deficit for implicit learning of the current serial reaction time task (within 1-2 weeks of the Session One) and this is consistent with previous study findings (Harrington et aI., 1990). Accuracy results also suggested that some PPO were not as accurate as individuals in other groups when general (non-specific) learning and retention were assessed. Some PWS showed a pattern of implicit learning quite different from individuals in other groups. The groups' divergent results provide preliminary evidence to negate Parkinson ' s-like basal ganglia damage as a possible etiological factor of stuttering. However these results do not precluding Giraud et al.'s (2008) hypothesis of cortical pathology perpetuated by cortico-striato thalamo-cortical connections associated with stuttering. PWS showed slow reaction times for initial trials of Session One and the Retention Session but "caught up" after practice, demonstrating that some PWS manifest delayed but not deficient general (non-specific) learning relative to individuals in other groups. The difficulty some PWS showed for acquisition and "re 20 acquisition of set" implicated cortico-striato-thalamo-cortical circuits known to be critical for this skill (Peigneux et a!., 2000). The findings of the current study are sufficiently promising to embolden further research investigating implicit learning and retention in populations with motor speech disorders. As a next step, it will be necessary to investigate how the manipulation of variables such as explicit instruction, practice, and feedback will influence learning and retention in disordered populations. Future research must also have greater generalizability to functional speech tasks and speech treatment techniques than the current study. 21 Acknowledgements We would like to acknowledge the Canadian Institute of Health Research for funding provided to the first author and a National Science and Engineering Research Council of Canada Grant provided to the second author. 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ManagemenJ ofMotor Speech Disorders in Children and Adults (3rd Ed.). Austin, TX: Pro-Ed. 31 Appendix A Dysarthria Rating Scale _ _ _ _ _ _ _ _(rater) _ _ _ _ _ _ _ _ _ _ (participant code) Pitch Low Normal Variation of Pitch Normal Lack of variation Steadiness of Pitch Normal Tremor Loudness Soft Normal Loud Rate of Speech Slow Normal Fast StresslEmphasis Pattern Normal Excess stress Nasality Hyponasal Normal HypernasaJ Laryngeal Harsh Normal Breathy Articulatory Precision Normal Reduced clarity High Intelligibility Percentage of clear words: 95-100% 85-95% 50-85% All clear Most clear < 50% More than Y:z clear Less than Y:z clear 32 AppendixB Unified Parkinson's Disease Rating Scale (Fahn, Elton, & Members of the UPDRS Development Committee, 1987) II. Activities of Daily Living 5. Speec" o= Normal. I = Mildly affected. No difficulty being understood . 2 = Moderately affected. Sometimes asked to repeat statements. 3 = Severely affected. Frequently asked to repeat statements. 4 = Unintelligible most of the time. Modified Hoehn and Yahr Staging (Hoehn & Yahr, 1967) STAGE 0 = No signs of disease . STAGE I = Unilateral disease . STAGE 1.5 = Unilateral disease plus axial involvement. STAGE 2 = Bilateral disease, without impairment of balance. STAGE 3 = Mild bilateral disease, with recovery on pull test. STAGE 4 = Severe disability, still able to walk or stand unassisted. STAGE 5 = Wheelchair bound or bedridden unless aided . ]) Appendix C Day One Questionnaire 1) Did you notice anything about the syllables? YES NO. If yes, what did you notice? 2) Circle the number that fits best with what you remember about the syllables . The syllables Always appeared In this order 1 The syllables Often appeared In this order 2 The syllables Sometimes appeared in This order 3 1) PO PI 2 3 4 5 2) PE PA 2 3 4 5 3)PIPA 2 3 4 5 4) PE PO PE 2 3 4 5 5) PA PO PE 2 3 4 5 6) PI PA PE 2 3 4 5 7) PE PO PA 2 3 4 5 8) PE PA PO PE 2 3 4 5 9) PA PO PI PA 2 3 4 5 10) PI PO PE PI 2 3 4 5 The syllables Rarely appeared In this order 4 The syllables Never appeared In this order 5 J' Appendix D - page one Day Two Questionnaire 1) Did you notice any1hing about the order of the syllables? YES NO. If yes, what did you notice? 2) What number describes your belief about the syllables during the experiment? Very sure Ihe syllables sometimes appeared in a predictable order Somewhat sure the syllables sometimes appeared in a predictab le order 1 2 Guess the syllables sometimes appeared in a prediclable order Somewhat Very sure sure the syllables Ihe syllables random appeared in random random order order order Guess Ihe syllables appeared in a appeared in 4 3) Sometimes the syllables were part of a repeating sequence and they occurred in a pred ictable order. Put the syllables in the correct order as well as you can . (PA, PA, PE, PE, PI, PI, PO, PO) 6 35 Appendix D - page two 4) Circle the number that fits best with what you remember about the syllables. part of the Guess this is part of the Guess this is not part of the sequence sequence sequence Very sure Somewhat this is part of the sure this is sequence Somewhat sure this is not part of the Very sure this is not part of the sequence sequence 4 A) PO PA 2 3 4 5 6 8) PE PO 2 3 4 5 6 C)PA PE 2 3 4 5 6 D)PIPE 2 3 4 5 6 E) PO PI PO 2 3 4 5 6 F) PE PI PA 2 3 4 5 6 G)PAPE PA 2 3 4 5 6 H)PI PO PA 2 3 4 5 6 I) PO PI PO PE 2 3 4 5 6 J) PE PI PA PE 2 3 4 5 6 K) PA PE PA PO 1 2 3 4 5 6 L) PI PO PA PE 1 2 3 4 5 6 5 6 36 Appendix E Session One Sequence Block repeated 4 x (Blockl, Block 2, Block 3 & Block 4) = Total 288 trials PO PI PO PE PI PA PE PA J 1 9 10 ~ II 12 PO PE PI 17 18 j , PO PE PI PA PE PA * - Break PO PI 19 14 IJ 15 16 PA PE PA PO PI 20 21 22 23 24 PO PE PI PA PE PA PO PI - Break 25 28 26 27 29 30 3I 32 PA PE P A PO PI PO PE PI 33 38 34 35 36 37 39 40 PA PE PA PO PI PO PE PI 41 46 42 43 44 45 47 48 PA PE PA PO PI PO PE PI - Break 49 54 50 5I 52 53 55 56 PI PA PE PA PO PI PO PE n ~ H 00 ~ ~ M ~ PI PA PE PA PO PI PO PE 6S 66 67 68 RAN I RAN 2 SEQ I SEQ2 69 70 71 72 RAN 3 SEQ 3 SEQ4 RAN 4 PI PO PE PA PO PI PA PE - Break S 5 SEQ 6 SEQ 7 SEQ 8 SE 9 SEQ lOS PA PO PI PI II SEQ 12 PI RAN 5 SEQ 13 SEQ 14 SEQ 15 RAN 6 SEQ 16 RAN 7 SEQ 17 PO PE PI SE PO PE PI PA PE - Break 18 SEQ 19 SEQ 20 SEQ 21 SEQ 22 SEQ 2J S PO PE PA PO PE RAN8 S 26 S PE 27 SEQ 28 SEQ 29 SE 30 RAN 9 SEQ31 PA S 24 SEQ 25 PA PE PO J2 RAN 10 RAN II SEQ J 3 SEQ 34 RAN 12 RAN IJ SEQ 35 PO PO RAN 14 RAN 15 SEQ 36 RAN 16 S PI PA PO PE - Break J7 17 SEQ 38 S 39 PO PI RAN 18 RAN 19 SEQ 40 SEQ 41 RAN 20 SEQ 42 SEQ 43 RAN 21 PE PI PA PE P A PO PI RAN 22 SEQ 44 SEQ 45 SEQ 46 SEQ 47 SEQ 48 SEQ 49 SEQ 50 Day One Questionnaire Note. *Statistical analysis included mean reaction time for the first two sequences of each sequence block. ** - indicates random items (RAN) which violate the sequence order 37 Appendix F Retention Session (Session Two) Sequence Block repeated Ix (Block 1 & Block 2) = Total 144 trials PE PA PO PI PO PE PI ,PA J 4 6 j PEPA PO PI POPE PI PA*-Break II 10 12 PO PE PI PI 19 20 17 18 PI PO PE PI 25 26 27 35 34 21 22 42 29 43 50 36 38 37 44 45 51 52 59 58 67 66 RAN I RAN2 SEQ I PI SE PO 40 60 68 SEQ7 55 56 PO PE PI 62 61 63 64 PO PE PI 70 69 SEQ2 RAN3 SEQ3 SEQ8 48 PO PE PI PO PE PA PO PI 5 SEQ6 PO - Break 47 54 53 PA PE PA PO PI 65 32 39 46 PA PE PA PO PI 57 31 30 PA PE PA PO PI 49 24 2J PA PE PA PO - Break PA PE PA PO PI PE PI 41 16 15 PA PE PA PO PI PE PI 33 28 14 13 PA PE PA PO 71 72 SEQ4 RAN4 PA PE - Break SE 9 SEQ 10 S PA PO PI PI II SEQ 12 PI RAN 5 SEQ 13 SEQ 14 SEQ 15 RAN 6 SEQ 16 RAN 7 SEQ 17 PO PE PI S PO PE PI PA PE - Break 18 SEQ 19 SEQ 20 SEQ 21 SEQ 22 SEQ 2J PO PE PA PO PE RAN 8 S 26 SE 27 SEQ 28 SEQ 29 S PA 30 SEQ31 PO PA PE SEQ35 PE - Break PO RAN 14 RAN 15SEQ36 RAN 16S PI PA 37 RAN 17SEQ38 SE 39 PO PI RAN 18 RAN 19SEQ40 SEQ 41 RAN 20 SEQ 42 SEQ43 RAN21 PE PI P A PE P A PO PI RAN 22 SEQ 44 SEQ 45 SEQ 46 SEQ 47 SEQ 48 SEQ 49 SEQ 50 Generate Task = Total 10 trials PE PA ? PO PI ? PE PI PA PE PA ? PA PO PI ? PE PI PA PE ? PI PA PE PI PO PE PI ? PI PA PO ? PI PO PE ? PA ? PI ? Day Two Questionnaire Note. *Statistical analysis included mean reaction time for the first two sequences of each sequence block. ** - indicates random items (RAN) which violate the sequence order Sequence Learning and Retention I Appendix G: Table 3 Mean (SD) Reaction Time in milliseconds for Control Participants (C) Group Session One Blocks 1 & 4 Differences b Retention Session Blocks 1 & 2 l.l1:ID ' .1l'Z.:1ll 4 (l-8) C1 1087 (325) 899 (169) C2 934 (060) 957 (090) C3 1272 (121) 1092 (242) C4 1033 (282) 913 (134) 4 (9-16) l.l1:ID 1 (9-16) 2 (1-8) 2 (9-16) Diff 1 Diff2 882 (090) 785 (164) 751 (099) 803 (137) 919 (124) 831 (134) 302 -34 -80 820 (080) 808 (087) 725 (123) 700 (106) 583 (091) 637 (224) 126 -83 88 1239 (143) 1193 (167) 859 (107) 652 (145) 740 (202) 680 (160) 80 -334 179 943 (241) 983 (098) 875 (103) 869 (070) 792 (084) 766 (058) 50 -108 109 Diff3 C5 1132 (201) 913 (179) 920 (170) 895 (151) 1015 (214) 1003 (226) 1025 (076) 965 (165) 237 120 50 C6 859 (248) 1176 (296) 1050 (341) 1158 (185) 858 (156) 853(210) 728 (115) 794 (120) -299 -301 64 C7 896 (232) 759 (091) 790 (156) 939 (064) 827 (116) 598 (278) 782 (147) 723 (120) -43 -112 104 C8 1223 (183) 1246 (150) 1073 (101) 1047 (175) 981 (364) 1062 (217) 176 -66 981 -68 C9 940 (225) 852 (078) 953 (187) 836 (154) 878 (334) 941 (180) 892 (073) 946 (164) 104 43 C10 1034 (256) 1000 (144) 791 (274) 804 (226) 797 (305) 742 (096) 779 (098) 822 (067) 230 -7 -26 C11 850 (084) 791 (127) 760 (153) 830 (126) 998 (391) 1055 (462) 1286 (231) 1240 (166) 21 168 -242 C12 930 (187) 797 (180) 1119 (215) 1004 (273) 874 (339) 882 (150) 906 (159) 867 (145) -74 -130 7 C13 1111 (271) 1048 (138) 815 (089) 783 (140) 894 (361) 1025 (215) 848 (161) 931 (160) 328 111 -37 C14 888 (202) 558 (290) 656 (140) 649 (138) 870 (331) 1015 (074) 971 (216) 1017 (221) 240 221 -147 MEAN 1014 (206) 929 (165) 915 (170) 908 (153) 871 (239) 871 (183) 866 (137) 863 (146) 106 -37 70 '(1-8) indicates Mean (SD) of trials 1 though 8, (9-16) indicates Mean (SD) of trials 9 through 16. b Diff 1 = Block 1 (1-8) - Block 4 (9-16), Diff 2 = Ret Block 1 (1-8)- Block 4 (9-16), Diff 3 = Block 1 (1-8) - Ret Block 2 (9-16) Sequence Learning and Retention· J Appendix G: Table 4 Mean (SD) Reaction Time (milliseconds) [or Persons who Stutter (PWS) Group Session One BlockS 1 & 4 1 (1-8] ' 1 (9-16J Differences b Retention Session Blocks 1 & 2 4 [1-8J 4 [9-16] 1 (1-8) 1 [9-16) 2 (1-8J 2(9-16) Oiff 1 OifCZ Diff3 PWS1 1353 (247) 1373 (284) 1049 (111) 1031 (082) 1191 (165) 989 (196) 1098 (160) 1011 (131) 321 160 180 PWS2 834 (150) 853 (134) 873 (132) 800 (079) 902 (056) 744 (345) 882 (119) 870 (071) 34 102 32 PWS3 1109 (251) 900 (111) 971 (208) 903 (185) 925 (109) 959 (144) 966 (125) 859 (106) 207 23 66 PWS4 992 (136) 982 (145) 831(061) 793 (036) 1272 (355) 1135 (352) 847 (181) 774 (153) 199 480 498 PWS5 1030 (131) 1061 (137) 781 (172) 729 (116) 845 (139) 820 (093) 787 (068) 733 (083) 301 116 112 PWS6 1034 (193) 888 (185) 608 (130) 628 (170) 740 (141) 829 (191) 836 (122) 836 (049) 406 112 7 PWS7 1253 (240) 1106 (136) 910 (075) 957 (156) 920 (120) 872 (173) 1258 (347) 1072 (210) 296 -37 84 PWS8 1061 (166) 1215(177) 809 (127) 862 (169) 984 (194) 1210 (163) 1027 (200) 951 (164) 200 123 -88 PWS9 996 (222) 69 899 (261) 1017 (163) 898 (132) 1020 (125) 899 (084) 791 (284) 733 (173) 98 122 PWS10 1243 (216) 1017 (232) 997 (231) 973 (185) 831 (268) 1059 (189) 827 (070) 768 (061) 270 -142 99 PWS11 902 (326) 689 (078) 680 (085) 727 (154) 837 (127) 936 (104) 858 (156) 417 47 -41 1097 (275) PWS12 1218 (349) 913 (419) 1054 (199) 951 (607) 827 (109) 894 (055) 938 (128) 846 (274) 268 -124 -31 PWS13 989 (137) 940 (141) 880 (103) 841 (058) 1029 (116) 1007 (155) 935 (093) 867 (089) 148 187 183 PWS14 1012 (237) 1028 (236) 902 (396) 873 (242) 895 (093) 905 (057) 703 (074) 771 (107) 139 22 28 MEAN 1006 (210) 884(156) 851 (164) 936 (153) 940(153) 916 (148) 854 (130) 236 085 086 1087 (211) • (1-8) indicates Mean (SO) of trials 1 though 8, (9-16) indicates Mean (SO) of trials 9 through 16. b Oiff 1 =Block 1 (1-8) - Block 4 (9-16), Oiff 2 = Ret Block 1 (1-8)- Block 4 (9-16), Oiff 3 = Block 1 (1-8) - Ret Block 2 (9-16) Sequence Learning and Retention'2 Appendix G: Table 5 Mean (SD) Reaction Time (milliseconds) for Persons with Parkinson's Disease (PPD) Group Session One Blocks 1 & 4 Diff~rence~ b Retention Session Blocks 1 & 2 1 (1-8)' 1 [9-16] 4 [1-8) PPDl 1387 (408) 1029 (271) 1137 (177) 4[9-16) 1 [1-8] 1 (9-16) 2 [1-8) 2 (9-16) Diff 1 Diff2 Diff3 1236 (173) 1315 (307) 1289 (264) 1052 (133) 1053 (107) 152 79 262 34 PPD2 990 (191) 937 (214) 610 (132) 629 (172) 915 (113) 857 (081) 793 (090) 881 (094) 360 286 PPD3 1137 (148) 1088 (111) 865 (082) 850 (142) 1052 (207) 932 (266) 955 (123) 889 (198) 287 202 163 PPD4 1301 (493) 997 (250) 1111 (157) 1399 (287) 978 (238) 972 (161) 1066 (118) 1083 (074) -98 -421 -106 PPD6 1014 (213) 941 (240) 907 (244) 873 (229) 729 (056) 715 (071) 633 (086) 705 (058) 141 -144 24 PPD7 1230 (296) 971 (252) 989 (172) 892 (143) 698 (240) 743 (128) 609 (216) 673 (224) 338 -194 26 PPD8 870 (085) 807(130) 748 (072) 765 (111) 754 (135) 842 (209) 954 (165) 1077 (235) 105 -11 -322 PPD9 1133 (300) 887 (244) 731 (164) 741 (171) 783 (246) 782 (244) 699 (086) 694 (106) 392 41 89 60 PPD10 902 (104) 932 (076) 1032 (170) 1031 (120) 927 (152) 887 (087) 863 (085) 867 (170) -129 -104 PPDll 1063 (289) 967 (189) 904 (304) 780 (125) 693 (194) 592 (150) 607 (164) 834 (103) 282 -88 -141 PPD12 1026 (165) 939 (250) 839 (098) 759 (079) 912 (100) 1053 (140) 1259 (184) 1056 (219) 267 152 -144 PPD13 999 (291) 870 (244) 933 (231) 991 (179) 857 (238) 1032 (365) 781 (156) 703 (127) 8 -134 154 PPD14 646 (277) 719 (388) 566 (102) 592 (147) MEAN 1053 (251) 929 (220) 866 (162) 888 (160) 884 (180) 866 (183) 856 (134) 876 (143) -028 008 054 166 '(1-8) indicates Mean (SD) of trials 1 though 8, (9-16) indicates Mean (SD) of trials 9 through 16. Diff 1 = Block 1 (1-8) - Block 4 (9-16), Diff 2 = Ret Block 1 (1-8)- Block 4 (9-16), Diff 3 = Block 1 (1-8) - Ret 810ck 2 (9-16) b " Sequence Learning and Retention 3 Appendix G: Table 6 Mean (SO) Reaction Time (milliseconds) for Control Participants (C), Persons who Stutter (PWS) and Persons with Parkinson's Disease (PPO) for Sequence-Specific Learning in Session One Partici~ant Controls PWS PPD Random' Sequence b Diff Random Sequence Diff Random Sequence Diff 946 (226) 848 (081) 098 1198 (200) 1109(317) 090 1393 (262) 1348 (241) 046 2 840 (097) 790 (089) 051 871 (117) 827 (110) 044 724 (156) 720 (164) 004 3 1220 (252) 1074 (134) 146 838 (083) 897 (074) -058 899 (258) 912 (108) -013 4 1052 (200) 939 (170) 113 939 (142) 931 (079) 008 1133 (130) 1166 (236) -034 5 1005 (168) 1018 (226) -013 893 (094) 946(147) -053 1321 (216) 1340 (196) -019 6 1176 (246) 1067 (095) 109 731 (165) 988 (199) -257 1100 (222) 1004 (117) 097 7 1276 (232) 946 (239) 330 941 (166) 891 (281) 049 1113 (256) 1140(218) -027 8 1038 (218) 912 (091) 126 779 (218) 835 (218) -056 764(140) 750 (103) 014 9 891 (200) 794(116) 098 984 (156) 1078 (199) -094 967 (124) 962 (241) 005 10 817 (223) 876 (252) -058 938 (140) 888 (133) 050 1157 (154) 1059 (112) 099 11 873 (107) 814 (101) 059 796 (114) 741 (091) 055 967 (146) 930 (247) 036 12 1125 (164) 1027 (179) 098 1219 (161) 1225 (186) -005 792 (125) 827 (202) -035 13 879 (098) 867 (102) 011 897 (227) 819 (121) 077 1161 (317) 1120 (249) 040 14 789 (175) 729 (058) 060 946 (299) 949 (225) -002 818 (273) 748 (227) 070 MEAN 995 (186) 907 (138) 087 926 (163) 937 (170) -011 1022 (198) 1002 (190) 020 • Mean (SD) of the first 16 random trial pairs from Block 5 (random block) of session one (values are rounded) b Mean (SD) of the first 16 sequence trial pairs from Block 5 (random block) of session one (values are rounded) c Difference =(random mean reaction time) - (sequence mean reaction time) Sequence Learning Wld Retention '4 Appendix G: Table 7 Mean (SO) Reaction Time (milliseconds) Jar Control Participants (C), Persons who Stutter (PWS) and Persons with Parkinson's Disease (PPD) Jar Sequence-Specific Learning on the Retention Test Particigant PWS Controls 2 PPD Random' Sequence" Diff Random Sequence Diff Random Sequence Diff 782 (135) 775 (193) 007 1111 (233) 1161 (211) -050 988 (126) 1048 (160) -050 807 (256) 690 (104) 118 966 (081) 909 (154) 056 850 (157) 870 (154) -056 3 719 (114) N/A 915 (122) 943 (149) -028 988 (232) 1028(216) -028 4 877 (147) 870 (105) 007 1002 (198) 914 (250) 088 1153 (157) 945(131) 088 5 1060 (132) 1044 (127) 016 898 (115) 748 (101) 150 1377 (221) 1201 (181) 150 6 796 (089) 812 (135) -016 875 (068) 866 (055) 008 703 (133) 623 (097) 008 7 921 (175) 782 (124) 139 1227 (538) 1099 (278) 129 884 (317) 622 (147) 129 1194 (197) N/A 984 (136) 1026 (176) -042 1174 (178) 1073 (304) -042 065 8 9 992 (206) 928 (206) 064 1015 (162) 950 (142) 065 982 (251) 848 (181) 10 832 (073) 874 (083) -042 810 (100) 788 (150) 022 960 (196) 834 (183) 022 930 (121) 724 (139) 611 (175) 037 11 991(118) 1143 (225) -152 893 (140) 037 12 1027 (212) 786 (156) 241 995 (306) 880 (202) 115 1161 (167) 1082 (151) 115 13 1021 (161) 991 (256) 030 945 (140) 860 (067) 085 834 (217) 803 (166) 085 14 1066 (185) 993 (162) 073 810 (131) 765 (124) 045 MEAN 915 (154) 914 (159) 040 963 (175) 914 (157) 048 983 (192) 891 (173) 040 'Mean (SD) of the first 16 random trial pairs from Block 5 (random block) of session one (values are rounded) b Mean (SD) of the first 16 sequence trial pairs from Block 5 (random block) of session one (values are rounded) 'Difference = (random mean reaction time) - (sequence mean reaction time) <, Sequence Learning and Retention'5 Footnotes 1 Stuttering is not traditionally categorized as a "motor speech disorder", though it has been so categorized by some researchers in the past (Kent, 2000). We acknowledge that there is continued controversy over the importance of many other variables besides motor control that may influence stuttering onset, persistence and manifestations. However, because of the undeniable difficulty in controlling motoric aspects of speech inherent to stuttering we felt justified in our classification for the purposes of this paper. 2 Despite investigators best efforts, one control participant dozed several times during the experiment and these approximately 70 (excluded) trials were not included in the above sum. As this participant was still one of the fastest control participants, the remaining trials of this drowsy participant, which were included in the analysis, had minimal, if any, negative effect on the group score. ) If the generate task stimuli were fPOI, fPI!, /?I, the correct answer would be PO, the foils would be PE and PA. PI was not a foil because PI never followed PI, not even in the pseudorandom condition and the participants understood this. 4 Exploratory post hoc analyses were performed. Three 2 (group) x 8 (Block) ANOVA (p = .05) were conducted to assess reaction times across Session One and the Retention Session for PWS vs. control participants, PPD vs. control participants and PWS vs. PPD. PWS' reaction times showed significant cubic polynomial contrasts relative to both control participants, F (1,23) = 4.5, P = .04, ~2= .16 and PPD, F (1,23) = 4.5, P = .05, ~2= .17. Although uncommon, we felt it was justified to conduct post hoc tests based on a near-significant comparison (p = .08), in the current study because this is an unprecedented explorative study with a relatively small sample size. Researchers have reasoned that a type 2 error is more dangerous than a type 1 error in this earliest stage of research (Portney & Watkins, 1993). Nevertheless the reader should be cautioned to the increased risk of type 1 error for these post hoc comparisons when interpreting these results. Sequence Learning and Retention (; Documentation of Author Roles: Documentation of Author Roles: Sarah Smits-Bandstra I. Research project: A. Conception, B. Organization, C. Execution 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique Vincent Gracco I. Research project: A. Organization, Execution 2. Statistical Analysis: A. Review and Critique 3. Manuscript Preparation: A. Review and Critique Runrung Head: CHUNKING AND STUTTERING Early stage chunking of finger tapping sequences by persons who stutter and fluent speakers Keywords: Chunking, Sequence, Practise, Stuttering, Finger Tapping Chunking and Stuttering 2 Abstract We explored the hypothesis that chunking differences underlie the slow finger-tap sequencing perfonnance reported in the literature for persons who stutter (PWS) relative to fluent speakers (PNS). Early stage chunking was defined as an immediate and spontaneous tendency to organise a long sequence into pauses, for motor planning, and chunks of fluent motor perfonnance. A previously published study in which 12 PWS and 12 matched PNS practised a 10-item finger tapping sequence 30 times was examined. Both groups significantly decreased the duration of between-chunk intervals (BCls) and within-chunk intervals (WCls) over practise. PNS had significantly shorter within-chunk intervals relative to PWS, but minimal differences between groups were found for the number of, or duration of, between-chunk intervals. Results imply that sequencing differences found between PNS and PWS may be due to differences in automatizing movements within chunks or retrieving chunks from memory rather than chunking per se. Chunking and Stuttering 3 Introduction Wingate (1969) stated the difficulty persons who stutter (PWS) experienced while speaking was not related to producing sound units for speech; rather the difficulty was in moving on from one element to the next. More recently Venkatagiri (2005) and Huinck, van Lieshoul, Peters and Hulstijn (2004) have suggested that PWS were slower and less accurate than fluent speakers (PNS) in their ability to pull from memory and concatenate (link) syllable sound units into a fluent sequence. In particular, Huinck et al. found that PWS differed from PNS in the fluent transition across syllable boundaries. The purpose of this research note was to investigate whether stuttering was associated with differences in sequence organization or 'chunking' of sequence elements with a focus on nonspeech movement. Neuroscience research has reliably shown that certain aspects of sequence organization are effector non-specific (Cohen, Ivry, & Keele, 1990; Hikosaka et aI., 1995; Hazeltine, Teague & Ivry, 2002). Basic motor programmes or synaptic tendencies are thought to be primarily housed in the roughly approximate 'homonculous' in either the articulator area (for speech movements) or the hand and finger area (for manual movements). However, it is well-established that the organization of these programmes/synaptic biases are supervised/developed according to input from subcortical structures such as the basal ganglia and cerebellum. These structures send timing/organization signals that are critical to most sequential movements regardless of whether they are eventually routed to hand or mouth execution areas of the motor cortex (Graybiel, 1998). Chunking and Stuttering 4 Nonspeech tasks were examined in the current research note because tbey have the additional advantage of avoiding confounds associated with top-down organization of syllables into meaningful words or syntactic units. Cbunking theory After practise, the performance ofa sequence of movements becomes increasingly integrated, with less hesitancies, false starts and errors (Lashley, 1951; Pew, 1966). The resultant well-practised movement is quick and fluent. It has been postulated that one way sequence production becomes increasingly fluent is through the process of 'chunking'. For the purposes of this research note chunking was defined as a continuing process where the composite elemental units of movement within a sequence become temporally linked into stable chunks of more than one unit of movement (Sternberg et aI., 1990; Klapp, 1995; Verwey & Dronkert, 1996; Immink & Wright, 2001 ; Klapp, 2003). Early stage chunking was defined more specifically as the immediate self-generated tendency to organise or 'chunk' a long sequence into shorter components. Unchunked , a sequence remains broken down into small independent units, is executed more slowly, and is more susceptible to errors as each transition is processed (Fisk & Schneider, 1984. Chunking is thought to be responsible for increased efficiency of processing, and increased fluency of sequencing performance over pratise (Newell & Rosenbloom, 1981; Fisk & Schneider, 1984). Chunking is also associated with enhanced memory retrieval for individual sequential movements so that performance is relatively impervious to interference from ongoing cognitive distractors (Schneider, Dumais, & Shiffrin, 1984; Logan, 1988). Klapp (2003) compared motor chunks to short-term memory chunks. As in memory, the motor chunk can be processed as a unit and fluent performance span is Chunking and Stuttering 5 based on the number of chunks regardless of the internal complexity or informational content of each chunk. Sakai, Kitaguchi, and Hakosaka (2003) stated that a chunk representation can overcome the limitation of working memory capacity by forming a hierarchical structure for many memory items. Enhanced memory retrieval reduces competing demands, alleviating processing bottlenecks and structural interference. Chunking processes INT Based on a series of robust reaction time studies, Klapp (1995) postulated the existence of SEQ and INT, two independent chunking processes. 'INT' generates a perceptual motor representations of single-chunk response elements and is thought to be dictated by underlying structural changes (including axon growth, synapse formation, etc,; Dariam-Smith & Gilber 1995; Karni, Meyer, Rey-Hipolito, Jezzard, Adams & Turner, 1998) that take place over several days/sessions of practise in both humans (Klapp, 1995; Verwey & Dronkert, 1996; Immink & Wright, 2001) and primates (Trembley et aI., 2009). INT is also responsible for retrieving old chunks from memory. INT processes are observable in simple reaction time studies with a single movement/chunk and are thought to be able to prepare single chunks in advance of a 'go' signal if the response is known. INT is hypothesized to be effector non-specific, unconscious, and responsible for automatization of chunks, or retrieving automatized chunks from memory. INT is thought to be observable in reduced pauses within chunks of movement (WCI) and within-chunk movement durations in longer sequences (Klapp, 2003). Chunking and Stuttering 6 SEQ Klapp (1995) further identified across-chunk motor programming as an effector independent, attention-demanding process entitled 'SEQ'. SEQ is an immediately apparent, hierarchical organization of multiple appropriate responses to a particular stimulus (Jimenez, 2008). This hierarchical plan is based on previous experience mapping stimuli to the individual components identifiable within a novel sequence (Darian-Smith & Gilbert, 1995; Karni et aI., 1998). SEQ is apparent in both explicit (conscious/declarative learning; Kock, Philip & Gade, 2006) and implicit sequence learning (unconscious/procedurallearning; Kock & Hoffman, 2000) and is highly consistent within an individual (Kermerly, Sakai & Rushworth, 2004). Several studies have readily observed practise effects in 'SEQ' processing over a single session as multiple movement elements/gestures were temporarily organised into chunks (Klapp, 1995; Immink & Wright, 2001; Klapp, 2003). SEQ processing is attention demanding, reflects plarming across chunks and can be inferred from pauses between movement chunks (BCI). Chunking in the literature Chunking theory has been consistently supported by many past studies which confirmed between chunk intervals (BCI) and significantly smaller within-chunk intervals (WCI) of maze tracing movements; Van Meir & Hulstien, 1993), writing and drawing movements (Hulstijn & Van Galen, 1983), finger tapping sequences (Taylor, 1943; Sternberg, Monsel, Knoll & Wright, 1978; lanacinski et a1., 1980; Garcia-Colera & Semjen, 1987; Stadler, 1993) and speech (Klapp, 2003). Based on results of the above studies researchers suggested that between-chunk intervals (BCI; related to SEQ processing) shortened reaction time by reducing the Chunking and Stuttering 7 demand for motor programming during the reaction time interval (Garcia-Colera & Semjen, 1987; Klapp, 1995; Immink & Wright, 2001; Klapp, 2003). Researchers further hypothesized sequences were executed more quickly when SEQ processing relegated motor programming to BCI rather than co-occurring/interfering with execution of ongoing movements (concurrent interference; Cohen et aI., 1990: Koch & Hoffman, 2000). In contrast, within-chunk intervals (WCI; related to TNT processing) decreased over successive practise trials as a complex response was organised into fewer but larger chunks over practise. Klapp (2003) hypothesized that processing based on SEQ is graduaUy replaced by INT processing to reduce reliance on attentive processing. Several studies have investigated SEQ and TNT processing by manipulating the manner in which participants subdivide sequences into chunks over practise. This was done several ways including predictably arranging repeated items within the sequence (Cohen, Ivry & Keele, 1990; Curran & Keele, 1993; Stadler, 1993), or arranging the timing of sequence item presentation into groups (Verwey & Dronkert, 1996). Although the existence of effectiveness of both TNT and SEQ chunking has been noted extensively in the literature, the self-generated process of chunking over practise for individuals (Verwey & Dronkert, 1996; Sakai et a., 2003) and patient populations (Doyon, 2008) has only recently come under investigation. Chunking and sequence learning in persons who stutter (PWS) A review of reaction times studies reveals many instances where PWS show slow simple reaction time for single movements/chunks relative to PNS, providing indirect evidence implicating inefficient INT processing (Smits-Bandstra, 2010). PNS' reaction Chunking and Stunering 8 times are most different from those of PWS when there is no/limited preparatory period, further implicating inefficient TNT processing (Klapp, 2003). However, PWS also show slow reaction times and durations for sequences of movements, implicating inefficient SEQ processing. For example, many studies have found poor overall speech (Watson & Alfonso, 1982; Peters, Hulstijn & Starkweather, 1989; Bishop, Williams, & Cooper, 1991 ; KJeinow & Smith, 2000; Smith & KJienow, 2000; Huink et aI., 2004) and nonspeech (Webster, 1986; Weinstein, Caruso, Severing &VerHoeve, 1989; Williams & Bishop, 1992) sequencing performance and, more specifically, poor sequence learning (Smits-Bandstra, De Nil & Rochon, 2006; Smits Bandstra, De Nil & Saint Cyr, 2006, Smits-Bandstra & De Nil, 2009) by PWS relative to PNS. Smits-Bandstra, De Nil and Saint Cyr (2006) compared the performance of PWS and PNS while practising a 10-item finger tapping sequence and a 10-item nonsense syllable sequence over practise. PWS demonstrated significantly slower reaction times for finger tapping and a trend for slower reaction times for syllable reading relative to PNS. PWS also demonstrated a trend for slower syllable sequence durations. In a dual task extension of this initial study, Smits-Bandstra, De Nil and Rochon (2006) reported PWS had significantly slower sequence durations for a 10-item finger tapping sequence in the single task condition relative to PNS. In another dual task extension of the initial study, Smits-Bandstra and De Nil (2009) also reported that the syllable sequence reaction times of PWS were significantly slower than those of PNS. Based on these results researchers have proposed that PWS may differ from PNS in the ability to organise speech and nonspeech movements into a fluent sequence (Wingate, 1969; Huink, van Lieshout, Peters & Hulstijn, 2004; Venkatagiri, 2005; Smits Chunking and Stuttering 9 Bandstra & De Nil, 2007). It remains to be determined whether differences in SEQ and/or !NT underlie the sequencing difficulties associated with stuttering. This information is of no little consequence as insight into specific deficient processes may point to neurological correlates of stuttering and suggest targeting of implicit vs. explicit training in treatment. Primary objective Based on review of the literature, we assumed that PWS showed slower reaction times and sequence durations relative to PNS due to difficulty with I) the timing or organization of chunks (related to SEQ processing), or 2) automatization of, and/or retrieval of chunks from memory (related to INT processing). We postulated that, if PWS were less efficient at timing or organization of chunks, BCI would be less frequent and oflonger duration in PWS relative to PNS (as is associated with ineffective SEQ processing). We further postulated that, if PWS were less efficient at INT processing, WCI would be oflonger duration in PWS relative to PNS (as is associated with ineffective !NT processing). It must be acknowledged that data described herein are derived from a previously published study not originally set up to manipulate chunking behaviors. Neither was the original study designed to identify SEQ vs. INT processing deficits. The main purpose of this research note was limited to observation of pOtential trends in specific early stage chunking processes by PWS and PNS during sequencing. This note served the purpose of alerting researchers to these trends and encouraging further empirical study in this area. Method Details of participant recruitment, ethics approval, screening and methodology can be found in a previously published study (Smits-Bandstra, De Nil & Rochon, 2006). Chunking and Stuttering 10 This study reported significantly slower reaction time and total sequence duration over practise for PWS relative to PNS. However, the timing and organization of individual sequential elements and inter-element durations over practise revealed in the current investigation have never been reported. Participants Twelve English-speaking males who stutter were matched for age and handedness and compared with 12 English-speaking male PNS. PWS scored in the very mild to moderate range (16.7 SO 6.8) on the Stuttering Severity Instrument-Ill (Riley, 1994). Participants reported hours per week spent typing as 3.8 SD 1.8, and 3.9 SD 1.8 for PWS and PNS respectively. Self-ratings of typing speed (2 slow, 6 average, 3 fast vs. 3 slow, 4 average and 4 fast) were reported for PWS and PNS respectively. Procedure Finger lapping sequence lask Participants were seated comfortably in front of a computer monitor. Participants were presented with an auditory 'ready' tone (a 1000 Hz tone for 500 ms) followed by a fixed interstimulus interval of 1500 ms and catch trials to prevent anticipatory reaction times. Participants were then presented visually with a I O-number sequence (3 1 3 2 4 I lil.D printed in black. Ten items were considered sufficient based on studies by Sakai et al. (2003). They were instructed to use the four fingers of their right (dominant) hand to press the four buttons arranged horizontally on a response box (Cedrus 610, Johnson, 1996) corresponding to the sequence of numbers on the screen. Participants were instructed to look at the monitor and not the response box in order to prevent visual feedback about their finger movements. Participants placed the index finger on the left most button (button I), the middle finger on button 2, etc. They were instructed to 'type Chunking and Stuttering II as fast you can without making mistakes' and to ' begin as soon as the sequence appears on the screen ' . The finger sequences disappeared as soon as the participants completed the sequence. The number sequence was designed so that no number triplet was used more than once, no number pair was used consecutively (e.g.l.l.lJ..), and no naturally occurring triplets were used (e.g. I 2 3 or 4 3 2). Thirty repetitions of the trial were considered adequate as the present study was limited to observing SEQ-type chunking in the earliest stages (within one session). Several previous studies have observed significant practise effects over 30 trials (Smits-Bandstra, De Nil & Rochon, 2006; Smits-Bandstra, De Nil & Saint Cyr, 2006; Smits-Bandstra & De Nil, 2009). Dependent variables and statistical analysis Chunking of a novel, arbitrary sequence of known constituent movements (button presses) was assessed over a single session of practise in the experiment examined. Dependent variables included reaction time, between-chunk intervals (BCI), within chunk intervals (WCI), as well as a number of BCI (number of chunks) and consistency of chunking patterns over practise. These dependent variables are well-established in the chunking literature (Klapp, 1995; Immink & Wright, 2001; Sakai et aI., 2003). Data regarding outliers and excluded error trials (minimal) are available in a previously published study. Participant groups did not differ in outliers, total accuracy, or accuracy patterns over practise (Smits-Bandstra, De Nil & Rochon, 2006). Sequences were divided into taps separated by within-chunk intervals (WCIs). WCI were measured as the time (in ms) from the fist button press to the second button press, or the second button press to the third button press, and so on to the tenth button Chunking and Stuttering 12 press. WCls were recorded online using the Superlab Pro 1.04 (Abboud & Sugar, 1997) software programme. Similar to previous studies (Sternberg et a!., 1978; Verwey & Oronkert, 1996) unusually large WCls were identified as BCI. Past studies employing short sequences (four items; Garcia-Colera & Semjen, 1987; Klapp, 1995; Immink & Wright, 2001; Klapp, 2003) defined BCls as those WCls that were more than one or two SOs above the mean WCI duration. However, SO was not an adequate threshold to identify BCI in the current study because our sequence was long and often contained more than one BCI. If there were two or more BCI the SO became very large and the BCI were not identified. Similarly, if there were no BCI and very little variability around the mean, WCI that were slightly larger than other WCI were mislabeled as BCI. Similar to Sakai et a!. (2003), we defined WCI and BCI in distributional, rather than absolute tenns so that the number and duration of scores did not mirror the group differences in duration already published. Z-tests were conducted to test the probability that a single WCI had a larger value than the rest of the WCI distribution for each participant, for each I O-item sequence. Only those WCI identified by z-tests as having a probability of95% or more of being larger than the rest of the WCI distribution were categorized as BCI. This high z-test probability criterion argued against the assumption that WCl and BCI were randomly varying values belonging to the same distribution of scores. Because the number of BCI and duration of BCI and WCI fell on a relatively nonnal distribution, it was deemed appropriate to define BCI based on z-tests of the raw scores. Chunking and Stuttering 13 Results One subject from each group (one PWS and one PNS) performed extremely poorly on the task and had reaction time, BCI and WCI values more than 2 SO from their respective group means. The data from these subjects were excluded from analyses. One PWS missed five sequences in a row (due to errors) and this resulted in an incomplete data set for this PWS, therefore most comparisons involved complete data from II PNS and 10 PWS. Number of BCI A 6 x 2 mixed ANOVA was used to assess the effect of the within-subjects factor of Practise (trial 1-5, 6-10, etc.) and the between subjects factor Group (PWS vs. PNS) on mean number of BCI per sequence. The 30 practise trials were subdivided into six equal groups of five (trial 1-5, 6-10, 11-15, 16-20,21-25, 26-30) to minimize transient fluctuations in performance. Practise effects were tested with polynomial contrasts to find the most reasonable description of continuous data. Such contrasts allow comparison of complex performance patterns across groups using linear, quadratic, cubic, quartic and other higher order contrasts (Portney & Watkins, 1993). Visual examination of a histogram suggested a good fit of the data to the normal curve. Assumptions of covariance, sphericity and equality of error variance were met. A significant quadratic Practise by Group interaction effect was found, F(5, 19) = 5.29, p = 1 .03, partial 1/ = .22. A trend for a quadratic Practise main effect was also found, F(5, 19) 1 = 4.15, P = .06, partial 1/ = .18. No Group main effect was found. Figure 1 displays the unique pattern PNS and PWS show for the number of BCI/chunks per sequence over practise. <insert figure I about here> Chunking and Stuttering 14 Reaction Time A 6 x 2 mixed ANOVA assessed the effect of the within-subjects factor of Practise (trial 1-5,6-10, etc.) and the between subjects factor Group (PWS vs. PNS) on reaction time. Reaction time was considered a special kind of BCI and was analysed separately from BCI duration. Visual examination of a histogram suggested a good fit of the data to the normal curve. Assumptions of covariance, sphericity and equality of error variance were mel. A significant quadratic Practise by Group interaction suggested that the reaction times of PNS improved significantly more quickly over practise relative to PWS, F(5 , \9) = 6.29, p = .02, partial 1/ 2 = 0.25 (see figure 2). A significant quadratic Practise effect, and a trend for a Group main effect was also found, F(5, 19) = 9.08, p = 2 2 .0 \, partial 1/ = 0.32 and F( I, 19) = 3.49, p = .08 , partial 1/ = .16, respectively . Both groups improved reaction times over practise, and PNS tended, on average to have shorter reaction times than PWS. <insert figure 2 about here> Duration of BCl A 6 x 2 mixed ANOVA was used to assess the effect of the within-subjects factor of Practise (trial \-5,6-10, etc.) and the between subjects factor Group (PWS vs. PNS) on BCI duration. Visual examination of a histogram suggested a good fit of the data to the normal curve. Assumptions of covariance, sphericity and equality were mel. Levene' s test indicated that in five of the six comparisons, the equality of error variance assumption was mel. A significant linear Practise by Group interaction, F(5, 19) = 5.42, 2 P = .03, partial 1/ = .22, indicated that PNS demonstrated shorter BCI, on average, relative to PNS for early practise trials only (see figure 3). A significant linear Practise Chunking and Stuttering IS main effect indicate{j the BCI durations of both groups became shorter over practise, F(S , 19) = 42 .91,p = .00, partial r/ = .69. No Group main effect was found . <insert figure 3 about here> Duration of WCI A mixed 2 x 6 x 8 ANOVA assesse{j the effect of Group (PNS vs. PWS), Practise (triall-S, 6-10, etc.) and WCI Position on sequence duration (WCIl = pause between I" and 2 nd button press, WCI2 = pause between 2nd and 3'd button press, etc.). Eight WCI positions were analyse{j including WCI2, WCB, WCI4 , WCIS, WCI6, WCl7, WCI9 and WCI I O. WCI I was analyse{j separately as reaction time and WCI8 did not have sufficient data to be analyse{j as it was use{j by the majority of participants as a BCI (only two subjects did not use WCI8 as a BCI) to analyse this position. Levene's test indicate{j unequal variances between the groups. A logarithmic transformation was used to successfully equalize group variance. Mauchley's test of Sphericity was significant therefore the Greenhouse Geisser Correction was applied to statistical results . Significant main effects of Practise (linear), F(S, 19) = 160.78,p = .00, partial r/ = .S4 and Group, F(I , 19) = 2.S,p = .01 , partial r/ = . \3, suggeste{j groups decreased WCI durations over practise and PNS' WCls were shorter than PWS' WCls. As shown in figure 4, a significant cubic Group x Practise interaction suggested that group differences were largest early in practise with PWS 'catching up' in later practise trials, F(S , 19) = 3.59, p = .02, partial ,.,2= . OS). <insert figure 4 about here> A significant Position main effect suggeste{j that WCI durations were dependent to some degree on where they occurred in the sequence, F(8, 138) = 7.30 , p = .01, partial ,.,2 = .OS. Post hoc analyses using Tukey's LSD indicated that WCI position 10 was Chunking and Stuttering 16 significantly shorter than all other positions while WCI position 9 was significantly shorter than WCI position 5 (see figure 5). No other contrasts were significant. <insert figure 5 about here> Discussion In previous studies PWS have shown slower reaction times and sequence durations relative to PNS (Smits-Bandstra, De Nil & Rochon, 2006; Smits-Bandstra, De Nil & Saint-Cyr, 2006). We postulated these results were due to difficulty with temporal organization of chunks (related to SEQ processing), or automatization of, and/or retrieval of chunks from memory (related to INT processing). Based on previous research we postulated that inefficient SEQ processing could be inferred from longer and less frequent BCI. We further postulated that inefficient INT processing could be inferred from longer WCI. Empirical testing of INT and SEQ processing was beyond the scope of this research note and any inferences made about SEQ and INT were based on comparison of results found in previous chunking studies. Nevertheless potential trends were observable in the post hoc analyses we conducted. Specifically, PWS demonstrated significantly longer WCI but not BCI relative to PNS. As stated in the introduction, BCI and WCI are not direct or sole indicators of SEQ or INT, respectively. With this caveat in mind, results of the current study can be interpreted to suggest that the INT processing of PWS appeared to be a promising avenue of future research. BCI One might expect fewer BCl (larger chunks) to evolve over pratise as this result is reported in the classic literature (e.g. Taylor, 1943). However previous studies examined chunking after extensive pratise while the current study reported immediate, early-stage Chunking and Stut1ering 17 changes in a single session (Jimenez, 2008). As expected due to limited practise, we found no significant changes in the number of BCI over pratise by either group. As described in the introduction, behavioral studies have confirmed that when BCI were incorporated into sequence training, sequence reaction time and overall sequence durations were shorter compared to sequences with no trained structure (Cohen, et aI., 1990; Koch & Hoffinan, 2000; Stadler, 1993; Verwey & Dronkert, 1996). Among other things, SEQ processing is thought to be associated with initiating BCI into a sequence, thereby decreasing reaction time and sequence duration. As reported previously by Smits-Bandstra, De Nil, and Rochon (2006), PNS demonstrated significantly faster reaction times and sequence durations (631.1 SD 200.5 and 3253.8 SD 946.9, respectively) relative to PWS (855.2 SD 298.8 and 3935.8 SD 1662.1, respectively). Results of the current analysis suggest that slow reaction times and sequence durations were not due to lack of BCI or slower BCI durations. From this result we can infer that this particular aspect of SEQ processing appeared relatively unaffected. WCI PWS had significantly longer WCI relative to PNS throughout the practise trials. Previous studies suggest that, among other things, WCI reflect aspects of INT processing, therefore we can infer from the current results that some aspect of PWS' INT processing may be less efficient than is typical. Research has not conclusively shown that BCI are solely programmed by SEQ, or WCI by INT. Therefore, at this time, we cannot entirely rule out potential inefficiencies in SEQ when differences in WCI are found. In addition, INT processes are thOUght to occur gradually, over the long term. The current experiment was only one session, providing a limited sample of potential changes ofINT with practice. The extent of practice should be considered in future chunking research. Chunking and Stuttering 18 Longer WCI durations may indicate that PWS take longer/more pratise to 'automatize' or bind together sequence elements, potentially having to initiate each segment individually. INT processing differences may also be due to inefficient retrieval of chunks from memory. Neuroimaging studies of PWS suggest atypical white matter underlying the primary motor area (REF), thought to be associated with movement chunk memories/programmes (REF). Neuroimaging studies of PWS have also implicated the cortico-striato-thalamo-cortical circuit (REF), though to be associated with automatization of movement (REF). !NT processing inefficiency associated with stuttering may be partially explained by these neurophysiological phenomena. Both SEQ and !NT processes are active during reaction time for sequential responses (Klapp, 2003). One explanation for the reaction time findings is that PWS' !NT process had difficulty retrieving chunks from memory. An alternative explanation is that PWS' SEQ process was able to instigate BCI appropriately , but only after a long reaction time delay . Potential Iy there were inefficiencies associated with both !NT and SEQ processes. It could also be argued that reaction time delays demonstrated by PWS (in this study and in previous studies; BIoodstein, 1995) are carried over to delays in the subsequent movement and/or movement transition after reaction time or a BCI. Because these results are tentative and based on exploratory post hoc analyses further research in this area is needed. Chunking Strategies One of the many possible explanations ofPWS' pattern of results is that PWS tended to rely on the more consciously controlled SEQ processing strategy during sequencing, rather than relegating chunks to more automatized !NT processing. There is cODsiderable support in the literature for the proposal that PWS tend to rely on attention Chunking and Stuttering 19 demanding, consciously controlled movement strategies (Bosshardt, 1999; Bosshardt, 2002; van Lieshout et aI., 1996,2004). The postulation that PWS continue to use executive motor control strategies serves as a viable explanation for the Group by Practice interaction for reaction time found in the current study. PNS were apparently able to quickly delegate motor control to automatized self-evolving INT processes, resulting in drastic reaction time reductions over the first few pratise trials. One possible interpretation of the current results is that PWS' chunking is primarily supervised by executive planning circuits with limited delegation to more automatic subcortical circuits (Graybiel, 1998; Trembley et aI., 2009). As a result, SEQ processing is relatively typical but INT processing is less automated (requiring increased planning and monitoring of executive planning centres), and susceptible to interference and competition for resources. Stutterers often report difficulty initiating or moving past the first element of a speech sequence (blocks, repetitions, prolongations). The speech of PWS is also slower (Max & Yudman, 2003), increasingly dis fluent as length and complexity of the sequence increase (Smith & Kleinow, 2000), and susceptible to concurrent tasks (Bosshardt, 2002). This makes sense if PWS have to initiate each element individually and/or plan the entire sequence at the beginning of the utterance. One could hypothesize that speech would be more susceptible to interfering tasks if it were consciously controlled rather than relegated to more automatized circuits. Conclusion and Future Directions A post hoc comparison of the sequencing performance of PWS and PNS revealed a potential trend indicating INT processing (automatizing and/or retrieving automatized Chunking and Stuttering 20 movement chunks from memory) rather than SEQ processing may be a promising avenue of future research. It is recommended that future investigations of INT processing examine simple reaction time and WCI of short sequences under conditions of extensive practise over several sessions to allow for automatization of chllilks. Differences in SEQ processing cannot be ruled out however. Further questions arise as to whether SEQ processing might be affected for non-repetitive stimuli. Figure 3 displays a significant Practise by Group interaction revealing that BCI durations were only different between PWS and PNS during the first few trials of the sequence. It is well known that stuttering frequency decreases for repeated stimuli (adaptation effect). A study designed to assess PWS' SEQ processing of novel sequences is merited, particularly as most speech is composed of novel sequences of known words and syllables. We analysed the consistency of BCI number but did not assess consistency of BCI position. This variable would be more appropriate to assess in short sequences with typically one BCI. Given the current findings, variability (of both number and placement ofBCl) in sequence organization is an interesting avenue for further investigation. Although the current data are analysed within a group model it is important to note that we found individual differences in the process of chunking over pratise. Our results indicated that, similar to previous studies (Sakai et aI., 2003; Verwey & Dronkert, 1996), the number of BCl differed across individuals and individuals demonstrated evidence of hypothesis testing using different BCl patterns across pratise trials. Chunking and Stut1ering Acknowledgments We would like to acknowledge editorial assistance from Sophie Lafaille. 21 Chunking and Stuttering 22 Declaration of interest We would like to acknowledge a grant from the Toronto Rehabilitation Institute to the first author and a grant from the Natural Science and Engineering Research Council of Canada to the second author. The post hoc analyses on the study described herein was funded by a Canadian Institute of Health Research grant to the first author. The authors report no conflicts of interest. Chunking and Stuttering 23 References References: Abboud, H., & Sugar, D. (1997) . SuperLab Experimental Laboratory Software (Version 1.04) (Computer software]. Phoenix, AZ: Cedrus Corporation. 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Number of between-chunk intervals (BCI) per sequence averaged across practice trials for participant groups (error bars represent I SO of intersubject variability). figure 2. Average finger sequence reaction time for participant groups over practice (error bars represent 1 SO of intersubject variability). figure 3. Average between-chunk interval duration (BCI) for participant groups over practice (error bars represent 1 SO of intersubject variability). figure 4. Average within-chunk intervals (WCI) for participant groups over practice (error bars represent I SO ofintersubject variability) . figure 5. Average duration of within-chunk intervals in all positions across the IO-item sequence (error bars represent 1 SO of intersubject variability). Chunking and Stuttering 3 ~-------------------------------------------------------- "5 j § z1.5 ~---------------------------------------------------------- 1 ~----------------------------------------------------------Practfce TrIals Praetice Trials Practlce Trials PractJc:e TrIals Practice Trials Practlce TrIals 1·5 6-10 11·15. 16-20 21·25 26-·30 figure 1. 28 Chunking and Stuttering 1300 1200 1100 i• 1000 ,~ :! := E 900 .E ~ 1= aDo iI: 700 c 600 " ~ ~ I ~"- ' ~ ..... -.~ .... 500 400 Practice Trials Practice Trials Practice Trials Practice Trials PracUce Trials Practice Trials 1-5 6-10 11·15 16-20 21·8 26-30 figure 2. 29 Chunking and Stuttering 1100 -A 1100 I ~1000 ..1 e ., 100 ! 1 ~ " i~ ~ Io.... .......... '&100 j '" aoo -. ....... ~ "" .... ~ PrKtIIf TrIaIa PI'Ktl<lI Tna PrKUaI T.... Pra*l Trial. Pfldlal 1-5 figure 3 . &-10 1145 18-2Q Tr1." 21-25 PI"Ktlal Trt4afs 21-30 30 Chunking and Stuttering soo T ! .11. '" '" .~ ~~ ~ -......., L. ~ ....... I 200 PractIce TrAI5 PractJot TrIa.b Practk:e Trial. practfQ Trtlll Practice Trials 1-6 6-10 11·15 15-20 J1"25 figure 4. p~ 'frqls 26030 31 Chunking and Stuttering ~o r------------------------------------------------------ 4~ +----------------------------------------r~-------------- 50 o WCl2 figure 5. Wet5 WCI6 WCI7 WC\4 wCla WCI9 Position of wlthln-ehunk Intervals within the 10-item sequence WCl3 WCl10 32