Posture-related oscillations in human cerebellar thalamus in essential tremor are enabled by voluntary motor circuits

Abstract

The mechanism of essential tremor (ET) is unclear. Animal models of tremor and functional imaging studies in ET predict that the cerebellum and a cerebellar recipient thalamic nucleus (ventral intermediate, Vim) should exhibit oscillatory activity during rest and during tremor due to abnormal olivo-cerebellar activity. Physiologic responses of 152 single neurons were recorded during awake mapping of the ventral thalamus in seven patients with ET prior to thalamotomy. During postural tremor, spectral cross-correlation analysis demonstrated that 51% of the neurons studied exhibited a concentration of power at tremor frequency that was correlated with electromyography, i.e., tremor neurons. During rest, thalamic neurons did not exhibit tremor-frequency activity. Among the three thalamic nuclei surveyed, Vim had a significantly higher proportion of tremor neurons than did the principal somatic sensory nucleus (ventral caudal, Vc) or a pallidal recipient thalamic nucleus (ventral oral posterior, Vop). Neurons related to active movement (voluntary neurons) had significantly greater tremor-related activity than did nonvoluntary neurons. These findings are not consistent with a model of continuous olivo-cerebellar driving of the motor cortex through thalamic connections. Instead ET may be facilitated by motor circuits that enable tremor-related thalamic activity during voluntary movement. Additionally, a subgroup of tremor neurons with proprioceptive inputs were identified that may allow sensory feedback to access the central tremor network.