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
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Hallett, M (2014) The dystonias: a heterogeneous collection. Eur J Neurol :
Wu, Tao; Liu, Jun; Zhang, Hejia et al. (2014) Attention to Automatic Movements in Parkinson's Disease: Modified Automatic Mode in the Striatum. Cereb Cortex :
Lungu, C; Malone, P; Wu, T et al. (2014) Temporal macrodynamics and microdynamics of the postoperative impedance at the tissue-electrode interface in deep brain stimulation patients. J Neurol Neurosurg Psychiatry 85:816-9
Ramos, Vesper Fe Marie Llaneza; Karp, Barbara I; Hallett, Mark (2014) Tricks in dystonia: ordering the complexity. J Neurol Neurosurg Psychiatry 85:987-93
de Campos, Ana Carolina; Kukke, Sahana N; Hallett, Mark et al. (2014) Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects. J Child Neurol 29:623-32
Pirio Richardson, Sarah; Beck, Sandra; Bliem, Barbara et al. (2014) Abnormal dorsal premotor-motor inhibition in writer's cramp. Mov Disord 29:797-803
Ferrazzano, Gina; Conte, Antonella; Fabbrini, Giovanni et al. (2014) Botulinum toxin and blink rate in patients with blepharospasm and increased blinking. J Neurol Neurosurg Psychiatry :
Hou, Yanan; Wu, Xuemin; Hallett, Mark et al. (2014) Frequency-dependent neural activity in Parkinson's disease. Hum Brain Mapp :
Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B et al. (2014) Reply: dystonia after severe head injuries. Mov Disord 29:578-9
Jinnah, H A; Berardelli, Alfredo; Comella, Cynthia et al. (2013) The focal dystonias: current views and challenges for future research. Mov Disord 28:926-43

Showing the most recent 10 out of 32 publications