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CORTICAL MOTOR MAPPING IN TOURETTE SYNDROME USING NEURONAVIGATED TRANSCRANIAL MAGNETIC STIMULATION Hilmar P Sigurdsson 1 , Prof. Georgina M. Jackson 2 & Prof. Stephen R. Jackson 1 1 School of Psychology, University of Nottingham, 2 Institute of Mental Health, University of Nottingham, United Kingdom. REFERENCES 1. Belluscio, BA, et al. Sensory sensitivity to external stimuli in Tourette syndrome patients. Mov Disord, 2011. 2. Schunke, O, et al. Quantitative sensory testing in adults with Tourette syndrome. Park Relat Disord. 2016 3. Kataoka, Y, et al. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. J Comp Neurol, 2010. 4. Kalanithi, PS, et al. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proc Natl Acad Sci U S A, 2005 5. Ziemann, U, et al. Decreased motor inhibition in Tourette’s disorder: Evidence from Transcranial Magnetic Stimulation. Am J Psychiatry, 1997 6. Gilbert, DL, et al. Association of cortical disinhibition with tic, ADHD and OCD severity in Tourette syndrome. Mov Disord, 2004 7. van de Ruit, M, et al. TMS brain mapping in less than two minutes. Braim Stimul, 2015. INTRODUCTION Patients with Tourette syndrome (TS) present heightened sensory sensitivity to sensory stimuli, without altered sensory thresholds 1,2 Studies have shown that TS is associated with impaired operation of GABA (inhibitory) signalling 3,4 and GABA-mediated cortical inhibition 5,6 For the first time in TS, this study focuses on cortical motor representation in TS and control subjects using neuronavigated TMS (nTMS) and non-grid based brain mapping method 7 We hypothesize that loss of GABA-mediated cortical inhibition within sensorimotor cortex leads to loss of separation and spatial specificity of TMS-induced muscle responses CONTACT DETAILS Email: [email protected] School of Psychology University of Nottingham University Park Campus East Drive Nottingham, NG7 2RD Office B31 ACKNOWLEDGEMENT We would like to thank Tourette’s Action for assisting with patient recruitment. METHODOLOGY Sixteen patients with TS (5 females, M age = 20.4 ± 7.1) and 14 control subjects (CS; 4 females, M age = 17.4 ± 3.9) participated in the study. Single pulse TMS was delivered across a 40 cm 2 area encompassing the left M1, partially overlapping with primary sensory and premotor cortices. Stimulus locations (coordinates) were simultaneously recorded with a neuronavigation software (BrainSight, Rogue Resolutions). MEPs were recorded from 5 different muscles Level of cortical inhibition was assessed using short-interval intracortical inhibition (SICI) with ISI of 3 ms. ANALYSIS MEPs were extracted from each muscle and synchronized with TMS coil coordinates offline. For each participant and each cortical motor map within a participant we calculated map parameters: Centre-of-Gravity (COG) Variability of muscle representation Separation between muscle pairs SICI was calculated using median MEP amplitude at each conditioning stimulus as a ratio of unconditioned trials. Group differences in map parameters were assessed using percentile bootstrapping CI (10,000 iterations). Multivariate regression was used to assess relationship between maps and median inhibition value observed for 3 ms SICI. RESULTS CONCLUSION Patient maps Control maps Figs 2-3. Cortical representation maps for each muscle studied. Top row is an example of maps from one control. Bottom row is an example of maps from one patient. Maps for all muscles are well defined. In this study we have shown the efficacy and feasibility of locating and outlining TMS-induced cortical muscle representations using a non-grid based method in 5 distinct muscles. Our results suggest an association between cortical muscle representations and measures of GABA-mediated inhibition in TS. Figs 4-6. Group comparison on map parameters. Far left: FDI muscle area is significantly smaller in TS. Middle: Separation of FDI and Masseter muscles is marginally increased in TS. Far right: Example of one muscle showing no group difference in centre-of-gravity. Fig 7. Group means for SICI (3 ms ISI). GABA-mediated inhibition as measured using 3 ms SICI. Patients and controls do not differ on any condition nor on overall median inhibition. Fig 1. Non-grid based TMS method was used to acquire cortical motor maps. Cortical maps were created based on TMS coordinates and EMG recordings. Fig 8. Multivariate regression with SICI median inhibition predicting variability of cortical muscle representations. Only the deltoid muscle shows a marginal relationship with SICI median inhibition.

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Page 1: CORTICAL MOTOR MAPPING IN TOURETTE SYNDROME USING … · 2017-06-26 · CORTICAL MOTOR MAPPING IN TOURETTE SYNDROME USING NEURONAVIGATED TRANSCRANIAL MAGNETIC STIMULATION Hilmar P

CORTICAL MOTOR MAPPING IN TOURETTE SYNDROME USING

NEURONAVIGATED TRANSCRANIAL MAGNETIC STIMULATIONHilmar P Sigurdsson1, Prof. Georgina M. Jackson2 & Prof. Stephen R. Jackson1

1School of Psychology, University of Nottingham, 2Institute of Mental Health, University of Nottingham, United Kingdom.

REFERENCES1. Belluscio, BA, et al. Sensory sensitivity to external stimuli in Tourette syndrome patients. Mov Disord, 2011.2. Schunke, O, et al. Quantitative sensory testing in adults with Tourette syndrome. Park Relat Disord. 20163. Kataoka, Y, et al. Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette

syndrome. J Comp Neurol, 2010.4. Kalanithi, PS, et al. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome.

Proc Natl Acad Sci U S A, 20055. Ziemann, U, et al. Decreased motor inhibition in Tourette’s disorder: Evidence from Transcranial Magnetic Stimulation. Am J

Psychiatry, 19976. Gilbert, DL, et al. Association of cortical disinhibition with tic, ADHD and OCD severity in Tourette syndrome. Mov Disord, 20047. van de Ruit, M, et al. TMS brain mapping in less than two minutes. Braim Stimul, 2015.

I N T R O D U C T I O N

⇲ Patients with Tourette syndrome (TS) present heightened sensory sensitivityto sensory stimuli, without altered sensory thresholds1,2

⇲ Studies have shown that TS is associated with impaired operation of GABA(inhibitory) signalling3,4 and GABA-mediated cortical inhibition5,6

⇲ For the first time in TS, this study focuses on cortical motor representationin TS and control subjects using neuronavigated TMS (nTMS) and non-gridbased brain mapping method7

⇲ We hypothesize that loss of GABA-mediated cortical inhibition withinsensorimotor cortex leads to loss of separation and spatial specificity ofTMS-induced muscle responses

CONTACT DETAILSEmail: [email protected] of PsychologyUniversity of NottinghamUniversity Park CampusEast DriveNottingham, NG7 2RDOffice B31

ACKNOWLEDGEMENTWe would like to thank Tourette’s Action for assisting with patient recruitment.

M E T H O D O L O G Y

⇲ Sixteen patients with TS (5 females, Mage = 20.4 ± 7.1) and 14 control subjects(CS; 4 females, Mage = 17.4 ± 3.9) participated in the study.

⇲ Single pulse TMS was delivered across a 40 cm2 area encompassing the leftM1, partially overlapping with primary sensory and premotor cortices.

⇲ Stimulus locations (coordinates) were simultaneously recorded with aneuronavigation software (BrainSight, Rogue Resolutions).

⇲ MEPs were recorded from 5 different muscles⇲ Level of cortical inhibition was assessed using short-interval intracortical

inhibition (SICI) with ISI of 3 ms.

A N A L Y S I S

⇲ MEPs were extracted from each muscleand synchronized with TMS coilcoordinates offline.

⇲ For each participant and each corticalmotor map within a participant wecalculated map parameters:⇲ Centre-of-Gravity (COG)⇲ Variability of muscle representation⇲ Separation between muscle pairs

⇲ SICI was calculated using median MEPamplitude at each conditioning stimulus asa ratio of unconditioned trials.

⇲ Group differences in map parameterswere assessed using percentilebootstrapping CI (10,000 iterations).

⇲ Multivariate regression was used to assessrelationship between maps and medianinhibition value observed for 3 ms SICI.

R E S U L T S

C O N C L U S I O N

Patie

nt m

aps

Cont

rol m

aps

Figs 2-3. Cortical representation maps for each muscle studied. Top row is an example of maps from one control. Bottom row is an example of maps from one patient. Maps for all muscles are well defined.

⇲ In this study we have shown the efficacy andfeasibility of locating and outlining TMS-inducedcortical muscle representations using a non-gridbased method in 5 distinct muscles.

⇲ Our results suggest an association betweencortical muscle representations and measures ofGABA-mediated inhibition in TS.

Figs 4-6. Group comparison on map parameters. Far left: FDI muscle area is significantly smaller in TS. Middle: Separation of FDI and Masseter muscles is marginally increased in TS. Far right: Example of one muscle showing no group difference in centre-of-gravity.

Fig 7. Group means for SICI (3 ms ISI). GABA-mediated inhibition as measured using 3 ms SICI. Patients and controls do not differ on any condition nor on overall median inhibition.

Fig 1. Non-grid based TMS method was used to acquire cortical motor maps. Cortical maps were created based on TMS coordinates and EMG recordings.

Fig 8. Multivariate regression with SICI median inhibition predicting variability of cortical muscle representations. Only the deltoid muscle shows a marginal relationship with SICI median inhibition.