Essential tremor severity and anatomical changes in brain areas controlling movement sequencing

Objective: Although the cerebello-thalamo-cortical network has often been suggested to be of importance in the pathogenesis of essential tremor (ET), the origins of tremorgenic activity in this disease are not fully understood. We used a combination of cortical thickness imaging and neurophysiological studies to analyze whether the severity of tremor was associated with anatomical changes in the brain in ET patients. Methods: Magnetic resonance imaging (MRI) and a neurophysiological assessment were performed in 13 nondemented ET patients. High field structural brain MRI images acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Cortical reconstruction and volumetric segmentation was performed with the FreeSurfer image analysis software. We used high-density surface electromyography (hdEMG) and inertial measurement units (IMUs) to quantify the tremor severity in upper extrimities of patients. In particular, advanced computer tool was used to reliably identify discharge patterns of individual motor units from surface hdEMG and quantify motor unit synchronization. Results: We found significant association between increased motor unit synchronization (i.e., more severe tremor) and cortical changes (i.e., atrophy) in widespread cerebral cortical areas, including the left medial orbitofrontal cortex, left isthmus of the cingulate gyrus, right paracentral lobule, right lingual gyrus, as well as reduced left supramarginal gyrus (inferior parietal cortex), right isthmus of the cingulate gyrus, left thalamus, and left amygdala volumes. Interpretation: Given that most of these brain areas are involved in controlling movement sequencing, ET tremor could be the result of an involuntary activation of a program of motor behavior used in the genesis of voluntary repetitive movements.