A major effort in the laboratory is devoted to understanding dystonia. Our fundamental view is that there is a deficiency of inhibition in central nervous system mechanisms in dystonia. Specifically, an important type of defective inhibition is surround inhibition, where muscles and movements not desired for the task need to be inhibited. Lack of inhibition leads to motor overflow and action dystonia. We are trying to identify the specific inhibitory circuit that contributes to surround inhibition. Studies are first done in normal subjects and then in patients. We have investigated a variety of inhibitory mechanisms already, and we are now engaged in understanding the premotor to motor cortex interactions and parietal to motor cortex interactions in focal hand dystonia. A specific project is ongoing to study the pathophysiology of the co-contraction that commonly characterizes dystonic movement. We are also exploring the physiology of motor learning in dystonia. Motor learning seems disturbed, and seems to have a principal role in producing focal hand dystonia since long term repetitive activity is certainly an etiological factor. In one type of experiment, we have been evaluating brain and spinal cord plasticity using brain and nerve stimulation paradigms. We are also conducting a case-control experimental study to evaluate long-term learning of sequential finger movements in focal hand dystonia patients. In order to study task specificity, we are engaged in some fMRI studies with various tasks and various limb effectors. We should hopefully identify which regions of brain are specific for a task, and then to see how this would malfunction in dystonia. Specifically we are studying patients with writers cramp. To gather further evidence for abnormalities in dystonia we are also exploring evidence for anatomical changes and for a deficiency of GABA-ergic mechanism. We are doing MRI studies with voxel based morphometry (VBM), diffusion tensor imaging (DTI), GABA magnetic resonance spectroscopy (MRS), anatomical imaging at 7 tesla, flumazenil PET studies and pathological studies of brains of patients with dystonia. The genetic markers in focal dystonia are largely unknown. Currently, we are evaluating patients with all forms of focal dystonia (blepharospasm, cranial dystonia, cervical dystonia, focal hand dystonia and spasmodic dysphonia) to look for a genetic marker. The study involves large families with focal dystonia and individuals without a family history. We have collaborators in the NIA for the genetics work. We will be cooperating with the multisite NIH sponsored Dystonia Coalition for further work in this area. We are also exploring further the physiology of Parkinson disease (PD). Although the sequence effect, the gradual reduction in size of movement, is one of the most common symptom in PD, its characteristics and etiology are largely unknown. With objective measurement, we have completed some studies of the clinical features and the beneficial effect of levodopa and repetitive transcranial magnetic stimulation, and we are now evaluating the behavioral features in more detail. Future plans call for a neuroimaging investigation. We are also studying gait freezing that, at least in some circumstances, relates to the sequence effect.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$1,358,052
Indirect Cost
City
State
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Wu, Tao; Zhang, Jiarong; Hallett, Mark et al. (2016) Neural correlates underlying micrographia in Parkinson's disease. Brain 139:144-60
Tinaz, Sule; Pillai, Ajay S; Hallett, Mark (2016) Sequence Effect in Parkinson's Disease Is Related to Motor Energetic Cost. Front Neurol 7:83
Foki, T; Vanbellingen, T; Lungu, C et al. (2016) Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study. Eur J Neurol 23:1301-7
Gallea, Cecile; Horovitz, Silvina G; 'Ali Najee-Ullah, Muslimah et al. (2016) Impairment of a parieto-premotor network specialized for handwriting in writer's cramp. Hum Brain Mapp :
Lopez, G; Bayulkem, K; Hallett, M (2016) Progressive supranuclear palsy (PSP): Richardson syndrome and other PSP variants. Acta Neurol Scand 134:242-9
Mak, Margaret K Y; Cheung, Vinci; Ma, Shuangye et al. (2016) Increased Cognitive Control During Execution of Finger Tap Movement in People with Parkinson's Disease. J Parkinsons Dis 6:639-50
Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver et al. (2015) Increased volume and impaired function: the role of the basal ganglia in writer's cramp. Brain Behav 5:e00301
Wu, Tao; Hou, Yanan; Hallett, Mark et al. (2015) Lateralization of brain activity pattern during unilateral movement in Parkinson's disease. Hum Brain Mapp 36:1878-91
Kukke, Sahana N; de Campos, Ana Carolina; Damiano, Diane et al. (2015) Cortical activation and inter-hemispheric sensorimotor coherence in individuals with arm dystonia due to childhood stroke. Clin Neurophysiol 126:1589-98
Hallett, Mark; Obeso, Jose (2015) Where does chorea come from? cortical excitability findings challenge classic pathophysiological concepts. Mov Disord 30:169-70

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