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). One previous functional imaging study was an fMRI investigation of patients with tremor, and results showed abnormally reduced activation in the temporoparietal junction region. 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. In our large on-going study, with help from our psychiatry colleagues, we are exploring the biopsychosocial underpinnings of functional movement disorders. 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. Neuroimaging studies show some abnormal connectivity even at rest, including from the temporoparietal junction region, and we are pursuing further analysis with graph theory analysis. We are currently studying changes in structural MRI in these patients including voxel-based morphometry and diffusion tensor imaging. Additionally, we are trying to make a functional model of brain networks in patients. We are also pursuing genetic and epigenetic abnormalities in a pilot study. We have published our findings of a polymorphism in a gene influencing serotonin that interacts with childhood trauma to influence clinical features of patients with functional movement disorders. We are completing a protocol (NCT04565080) which encompasses a study of our patients with functional movement disorders, evaluating how they are impacted by the pandemic. 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). The findings published this year show that these two types of tremors can be differentiated with measures looking at variability of the tremors and behavior of antagonist muscles. The overall study also includes neuroimaging to look for additional differences. In another physiological investigation, we are trying to understand why tremor amplitude diminishes when persons with essential tremor put their hands together to perform a task. We have also been investigating the pathophysiology of patients with myoclonus from sialodosis (NCT00001367). In collaboration with other groups, we are also studying the pathophysiology of mirror movements, ataxia in SCA7, and chronic fatigue syndrome.