Introduction: The ventral intermediate nucleus of the thalamus (VIM), a key link between the cerebellum and the sensorimotor cortex, has long been a neuromodulatory target for pathologic tremor. Stimulation of VIM can dramatically reduce tremor in these patients; however, the underlying mechanisms by which VIM modulates motor output are poorly understood.
Methods: We obtained VIM single-neuron recordings from 6 essential tremor patients during DBS electrode implant surgery. Waveforms surpassing a voltage threshold were sampled at 40 kHz and sorted using principal components. During recording, patients performed an 8-direction “center-out” task using a joystick to move a cursor to a target positioned around a circle. On some trials, the target jumped to a new location just after movement onset. Statistical significance for all findings was determined by comparing empirical values to a null distribution generated using non-parametric bootstrap methods.
Results: Each neuron was tested for task-related responsiveness by comparing baseline firing rates to firing rates cued to specific task-related events. Of 59 neurons recorded, ~50 percent responded to at least one task-related visual cue or motor event. Multiple subsets of responses were categorized, including responses selective for visual cues or motor events. Other neurons demonstrated similar responses to both visual and motor events, suggesting that these neurons may be involved in visual motor transformation. Approximately 20 percent of all neurons exhibited classical directional tuning. A small subgroup of neurons responded significantly more to the appearance of a “jumped” target and the associated movement correction. These neurons may be directly related to the transmission of a motor error correction signal.
Conclusions: VIM neurons were actively engaged by this joystick movement task, and many were tuned to the direction of movement. Several also selectively responded to corrections of movement, supporting a role for the VIM in conveying alterations in motor plans from the cerebellum to the cortex.
Patient Care: This research examines the role of individual neurons in patients with essential tremor, the most common movement disorder. A more complete understanding of these signals will help identify the mechanisms responsible for pathologic tremor generation in this patient population. These foundations may ultimately contribute to the development of closed loop DBS systems for essential tremor.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the role of the VIM thalamus as a link between cerebellar and cortical motor systems 2) Discuss, in small groups, the possible significance of visual and motor related signals in the VIM 3) Understand direction tuning in the VIM in the larger context of direction tuning prevalent throughout the motor system