Pathophysiology of Involuntary Movements and Volitional Disorders

National Institute Of Neurological Disorders And Stroke

Investigators

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Abstract

The pathophysiology of functional (psychogenic) movement disorders (FMD) is very poorly understood. These disorders are common in the population, diagnosis is difficult and treatment typically ineffective. We are studying the mechanisms underlying these disorders using cognitive tasks, neurophysiological testing, psychiatric measures, and functional imaging. One functional imaging study was an fMRI investigation of patients with tremor, and results showed abnormally reduced activation in the temporoparietal junction region. We have initiated similar studies in patients with functional myoclonus. We are also looking for abnormal activations related to tasks that probe functions such as emotional expression and movement inhibition, and have already shown abnormal activation in the amygdala. Recently, we have been studying fear conditioning, which is mediated by the amygdala. We have also investigated these patients for their sense of agency during fMRI studies, similar to the way we have studied normal subjects. In a large on-going study, with psychiatric help, we are exploring the biopsychosocial underpinnings of functional movement disorders. We showed that there is no abnormality of diurnal cortisol levels; however, studies of heart rate variability show abnormal vagal function. Neuroimaging studies show some abnormal connectivity even at rest, including from the temporoparietal junction region. The origin of tics is generally unknown, and we have been approaching physiology in several ways. Tourette syndrome patients report premonitory urge and other sensory abnormalities associated with the presence of tics. We have been studying tic genesis with functional neuroimaging and EEG, and have pursued in the past a series of studies looking at the physiology of the sensory urge. We will also be seeing if we can influence urge with brain stimulation and/or with functional magnetic resonance imaging feedback. On the basis of the idea that tics may represent bad habits, we are looking at the speed of making and breaking different types of behavioral choices. For many years, we have been collecting families with essential tremor looking for possible genetic abnormalities. This work is being pursued with additional sequencing in conjunction with Drs. Camilo Toro, Lev Goldfarb, David Goldman and Andrew Singleton. While it is known that many patients with essential tremor respond to ethanol, it is not clear how many and what the physiology of the response is. We are investigating this including TMS measures of cortical excitability. We have also been looking at the clinical neurophysiology of essential tremor and comparing it with similar measures in dystonic tremor.