Reduced dynamic range to tune the sensory-motor coupling on the left, at least in males who stutter

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1 Updated Perspectives on the Neural Bases of Stuttering: Sensory & Motor Mechanisms Underlying Dysfluent Speech Reduced dynamic range to tune the sensory-motor coupling on the left, at least in males who stutter Disclosure I have no relevant financial or nonfinancial relationship(s) within the products or services described, reviewed, evaluated or compared in this presentation. Nicole Neef University Medical Center Göttingen, Germany Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany 2013 ASHA Convention November Chicago, Il

2 Who stutters? The stutter demon Epidemiology Yairi & Ambrose, 2005 occurs in childhood without obvious reason heritable, epigenetic manifests around the age of 3 affects 5 % of children 3 of 4 children recover failure of recovery yields a prevalence of 1% in adulthood Andi, 9 years

3 What is known about the cerebral dysfunction in stuttering? 1. Altered lateralization (for a review see Ingham 2012) 2. Altered time course (Salmelin 2000) 3. Disconnection (Sommer 2002, Watkins 2008, Chang 2008; Kell 2009, Cykowski 2010) 4. Basal ganglia dysfunction (e.g. Giraud 2008, Watkins 2008) adapted from Kelly et al. 2010

4 What is actually going wrong when stuttering occurs?

1999 left ward asymmetry in all males left ward asymmetry in 3 females Caspars et al.

5 Anatomic left-right and gender differences in Broca s region and IPC-PFcm Grey level index - cell packing density Cytoarchitectonic volume Amunts et al left ward asymmetry in all males left ward asymmetry in 3 females Caspars et al left-volume increase in males rigth-volume increase in females putative correlate of the functional lateralization of speech production

6 J + Fluent speakers 34 (17 ) Adults who stutter 31 (15 ) 1.5 h MRI examination 3 x 9 minutes functional MRI 6 s Study design 18 s 6 s 18 s + 6 s Statistics FSL (1) first-level- analysis fixed-effects analysis speaking>singing (2) higher-level-analysis 2 x 2 random-effects ANOVA

7 Group x Gender Interaction of the contrast speaking > singing Putamen Operculum BA44-BA6/M1 A1, HG, PT Insula primary somatosensory cortex anterior intraparietal sulcus anterior intraparietal sulcus FWER; Z > 2.0; p < 0.05

The parietal lobe organization appears to

part of pre-wired chains coding the whole

Rizzolatti, 2006 signal change in left BA

8 The parietal lobe organization appears to be extremely well suited for providing fluidity in action execution. The neurons coding motor acts appear to be part of pre-wired chains coding the whole action. Rizzolatti, 2006 signal change in left BA 44-6 signal change in left IPS control adults who stutter control adults who stutter Kelly et al. 2010

9 Summary I Males who stutter show a less pronounced/lacking left lateralization of the sensory-motor network Females who stutter show a strikingly increased involvement of the left IPL-PFcm which is not in line with general gender differences in this area. Is this gender and stuttering specific? Future studies need to consider these ample gender effects

10 When speech gestures do not fire ignition problems in the human primary motor cortex

11 Primary motor cortex contains complex networks for excitability regulation intracortical inhibitory and excitatory networks Ramon y Cajal

12 Primary motor cortex - orchestrates movements Netter 1987 Netter 1987

13 When speech gestures do not fire ignition problems in the human primary motor cortex Study 1: Study 2: To proof the efficiency of inhibitory and excitatory circuits in the primary motor tongue representation To investigate the influence of speaking on the excitability regulation in the primary motor tongue representation

14 Transcranial Magnetic Stimulation Strong, brief magnetic pulse inducing a short current in the underlying neural tissue.

15 Motor Evoked Potential contralateral EMG recording Amplifier ipsilateral see also Rödel 2003

individual trials Inhibition conditioned MEP inter-stimulus

16 TMS-induced modulation of the excitability of the primary motor cortex unconditioned Motor Evoked Potential average individual trials Inhibition conditioned MEP inter-stimulus interval 2 ms Facilitation conditioned MEP inter-stimulus interval 10 ms

Proof of efficiency of intracortical inhibitory and excitatory circuits normalized MEP amplitude ± SE (%) Facilitation Inhibition inter-stimulus interval (ms) Adult fluent

17 Proof of efficiency of intracortical inhibitory and excitatory circuits normalized MEP amplitude ± SE (%) Facilitation Inhibition inter-stimulus interval (ms) Adult fluent speakers ( n = 14) Intracortical inhibition bilateral ISI 2 and 3 ms Intracortical facilitation bilateral ISI 10 and 15 ms Neef et al. Clin Neurophysiol, 2011 see also Muellbacher 2001

18 Proof of efficiency of intracortical inhibitory and excitatory circuits normalized MEP amplitude ± SE (%) Facilitation Inhibition inter-stimulus interval (ms) Adults who stutter ( n = 12) Intracortical inhibition left normal right reduced p = (Interaction Group x ISI x Hemisphere) Intracortical facilitation bilaterally reduced p = (Effect of Group) Neef et al. Clin Neurophysiol, 2011

19 Speech-induced modulation of the excitability of the primary motor cortex baseline TMS test TMS +! rest blasen silent reading preparation prolongation auf proceed blasen

20 Increase of motor cortex excitability in the transition phase Fluent controls (n = 13) Adults who stutter (n = 13) Transition phase Target gesture Neef, Hoang et al. (in preparation)

Summary and conclusion 1. Fluent speakers exhibit a leftlateralized facilitation during speaking 2. Adults who stutter show a lack of facilitation during coding of speech movements 3.

21 Summary and conclusion 1. Fluent speakers exhibit a leftlateralized facilitation during speaking 2. Adults who stutter show a lack of facilitation during coding of speech movements 3. Adults who stutter exhibit a bilaterally reduced dynamic range of excitability modulation adapted from Kelly et al Reduced dynamic range to tune the sensory-motor coupling on the left, at least in males who stutter

Acknowledgments Clinical Neurophysiology, UMG Göttingen

and Selforganization, BCCN, Göttingen Dr. rer. nat. A.

M. Wilke MPI for Human Cognitive and Brain Sciences,

Alfred Anwander Financial Support GGNB Göttinger

22 Acknowledgments Clinical Neurophysiology, UMG Göttingen Prof. Dr. med. M. Sommer, Prof. Dr. med. W. Paulus cand. med. T. N. L. Hoang, cand. med. Ch. Buetfering Institut of the Kassel Stuttering Therapy Dr. med. A. Wolff von Gudenberg, Kristina Jung (MA) MPI for Dynamics and Selforganization, BCCN, Göttingen Dr. rer. nat. A. Neef Kognitive Neurology, Göttingen Prof. Dr. rer. nat. M. Wilke MPI for Human Cognitive and Brain Sciences, Leipzig Dr. rer. nat. Alfred Anwander Financial Support GGNB Göttinger Graduate School for Neuroscience and Molecular Bioscience BFNT Bernstein Focus Neurotechnology Georg August University Dorothea Schlözer post doctoral fellowship DFG NE 1841/1-1

Speech dynamics are coded in the left motor cortex in fluent speakers but not in adults who stutter

doi:.9/brain/awu9 BRAIN 5: 8; 7 75 7 Speech dynamics are coded in the left motor cortex in fluent speakers but not in adults who stutter Nicole E. Neef,,, T. N. Linh Hoang,, Andreas Neef, Walter Paulus