Cortical and subcortical mechanisms in persistent stuttering ...

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To control for group differences in the finger tapping performance before rTMS we compared the individual mean baseline asynchrony values using a two-way mixed design analysis of variance (ANOVA) with the between-subjects factor group (AWS/AWNS) and the within- subjects factor hand (left/right). A similar ANOVA was calculated with the baseline ITIvariability. At baseline finger taps preceded the acoustic signal in most participants resulting in negative asynchrony values. However, there were two AWS and seven AWNS that showed a positive asynchrony in most runs. To test the impact of rTMS we therefore normalized the asynchrony after stimulation for each participant and each session by subtracting the asynchrony before stimulation. We entered the normalized values in a three-way mixed design ANOVA with the betweensubjects factor group (AWS/AWNS) and the within-subjects factors stimulation site (rTMS over the left PMd/rTMS over the right PMd) and hand (left/right). In addition, the expected rTMS-induced increases of asynchrony values (Pollok et al., 2008) were tested with onetailed t-tests. We tested the impact of rTMS on ITI-variability similarly by entering the normalized to baseline values. To exclude differences of age between groups we used a two-tailed t-test for independent samples, for education, handedness and percentage of stuttered syllables, we used Mann- Whitney U-tests. Nonparametric testing was chosen since education is an ordinally scaled variable and handedness as well as percentage of stuttered syllables did not show normal distribution in AWNS. The AMT comparison was calculated with a repeated measures ANOVA with hand as a within-subjects factor and group as a between-subjects factor. Statistics were performed by SPSS Statistics 17.0 (http://www.spss.com/de/software). Results At baseline the two-way mixed design ANOVA with asynchrony values before rTMS as dependent variable revealed no significant difference between AWS and AWNS (factor group F1,27 = 1.4, p = .3). However, the ANOVA revealed a more pronounced negative asynchrony in the right hand than in the left hand [factor hand F1,27 = 7.73, p = .01; left hand -28 ± 52 msec (mean ± SD) vs right hand -39 ± 60 msec]. Analysis yielded no further effect. ITI- variability before rTMS revealed no main effect or interaction for group and hand. After rTMS, the analysis of normalized asynchrony values revealed no main effects of hand (F1,27 = 1.5, p = .2), stimulation site (F1,27 = .4, p = .5) and group (F1,27 = .6, p = .4) but a significant interaction between hand, stimulation site and group (F1,27 = 5.82, p = .023). 40
Chapter 2 Study 1 Non-speech motor processing in stuttering Post hoc one-tailed t-tests, not corrected for multiple comparisons (Perneger, 1998), revealed that rTMS over the left PMd significantly increased left hand asynchrony in AWNS (T = 1.9, p = .036) as previously shown (Pollok et al., 2008). By contrast, in AWS rTMS over the right PMd resulted in a significant increase of left hand asynchrony (T = 2.34, p = .015) (Fig. 1). Please insert Fig. 1 about here After rTMS the analysis of normalized ITI-variability revealed no main effects of group, stimulation site or hand and no interactions of any of these factors. Interaction between group, hand and stimulation site was marginally significant (F1,27 = 5.82, p = .06). Post-hoc onetailed t-tests, not corrected for multiple comparisons, yielded in an increased normalized ITIvariability after rTMS over the left PMd in the left hand of AWNS (T = -2.01, p = .032). This is in concordance with previous findings (Pollok et al., 2008). All other statistics yielded no significant differences (Fig. 1). Discussion We studied the cortical control of auditory paced finger movements in AWS and AWNS. In AWNS, rTMS over the left PMd increased left hand asynchrony and increased ITI-variability, whereas rTMS over the right PMd was ineffective. By contrast, in AWS rTMS over the left PMd was ineffective, whereas rTMS over the right PMd prolonged left hand asynchrony. Left-hemispheric dominance on movement timing control in AWNS In AWNS rTMS over the left PMd increased asynchrony and ITI variability of the left hand. This finding agrees well with previous studies confirming a particular role of the left PMd in auditory paced rhythmic finger tapping (Pollok et al., 2009; Pollok et al., 2008). Although it is not entirely clear via which connections the left PMd exerts dominance over the right hemisphere, a specific significance of direct left PMd – right M1 connections (Pollok et al., 2008); (Boroojerdi et al., 1996; Ferbert et al., 1992) as well as subcortical circuits (Chouinard et al., 2003) has been evidenced. It is well established that the cerebellum is closely connected to the cerebral cortex via a cerebello-thalamo-cortical loop (Horne and Butler, 1995) and that auditory paced isochronous tapping engages the cerebellum (Ivry et al., 2002; Spencer et al., 2005). Even perception of an isochronous rhythm involves the left PMd in concert with the right cerebellum in healthy subjects suggesting the engagement of prediction mechanisms that 41
Page 1 and 2: Cortical and subcortical mechanisms
Page 3: Statement of Originality I hereby d
Page 6 and 7: Appendix B - Stuttering and acquire
Page 8 and 9: PM premotor cortex PMd dorsolateral
Page 10 and 11: addition I conducted an fMRI study
Page 12 and 13: movements which enable a fast detec
Page 14 and 15: aforementioned description of the s
Page 16 and 17: encoding lexical, grammatical, phon
Page 18 and 19: 1.5.1 The cerebral dominance hypoth
Page 20 and 21: motor hand area in adults who stutt
Page 22 and 23: Figure 1-1 from Mink, 1996: Schemat
Page 24 and 25: dystonia (Berardelli et al., 2008).
Page 26 and 27: Table 1-2 Results from diffusion te
Page 29: Chapter 2 Original articles 2 Origi
Page 33 and 34: Chapter 2 Study 1 Non-speech motor
Page 39: Chapter 2 Study 1 Non-speech motor
Page 59: Chapter 2 Study 1 Non-speech motor
Page 63 and 64: Chapter 2 Study 2 Excitability of t
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Chapter 2 Study 2 Excitability of t
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Chapter 2 Study 2 Excitability of t
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Chapter 2 Study 3 Phoneme Categoriz
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Chapter 4 Conclusions and future pr
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include the conceptualizer, the for
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ω σ´ σ σ st� t� r�� Fi
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Figure A-5 Directions into velociti
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associated with dysarthria, aphasia
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Table B-2 Tuning of fluency by Deep
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A Appendix C Appendix C - Psycholin
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are useful tools to investigate int
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Benabid AL, Pollak P, Louveau A, He
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De Nil LF, Kroll RM, and Houle S. F
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Hickok G and Poeppel D. The cortica
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Levelt WJM. Speaking: from intentio
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Neef N, Paulus W, and Sommer M. Dem
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Smith A and Kelly E. Stuttering: A
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160 unilateral left subthalamic bra
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I thank Tibor Auer for his constant
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