Pathophysiology of Involuntary Movements and Volitional Disorders

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

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 (NCT00500994). Previous functional imaging studies include an investigation of patients with tremor showing abnormally reduced activation in the temporoparietal junction region reflecting the involuntary nature of the disorder and a study probing emotional expression showing abnormal activation in the amygdala. Neuroimaging studies show some abnormal brain connectivity even at rest, including from the temporoparietal junction region, and we are pursuing further analysis with graph theory analysis. Structural imaging has also shown abnormalities of the amygdala, and we are currently pursuing this further with shape analysis. We are finalizing a study of diffusion tensor imaging that shows abnormal connectivity from the amygdala, further demonstrating the importance of this structure. Given the wealth of information we have acquired, we are trying to make a functional model of brain networks in patients with FMD. In our large on-going study of FMD, with help from our psychiatry colleagues, we are exploring its biopsychosocial underpinnings. We have shown that women who experience sexual trauma in childhood are more likely to develop a functional disorder than men who experience sexual trauma; this helps explain the observation that functional disorders are more common in women. We are also pursuing genetic and epigenetic abnormalities. We have published our finding of a polymorphism in a gene influencing serotonin that interacts with childhood trauma to influence clinical features of patients with functional movement disorders. 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 (NCT03223623). We have published previously that these two types of tremors can be differentiated with measures looking at variability of the tremors and behavior of antagonist muscles. We are now finalizing additional work with further physiology and neuroimaging. In another physiological investigation, showed why tremor amplitude diminishes when persons with essential tremor put their hands together to perform a task (NCT03027310). This is due to a change in motor control mechanisms with bimanual movements. We have also been investigating the pathophysiology of patients with myoclonus from sialidosis (NCT00001367). In collaboration with other groups, we are also studying the pathophysiology of mirror movements in Moebius syndrome, ataxia in SCA7, and chronic fatigue syndrome.