Effects of human cerebellar thalamus disruption on adaptive control of reaching.

Lesion or degeneration of the cerebellum can profoundly impair adaptive control of reaching in humans. Computational models have proposed that internal models that help control movements form in the cerebellum and influence planned motor output through the cerebello-thalamo-cortical pathway. However, lesion studies of the cerebellar thalamus have not consistently found impairment in reaching or adaptation of reaching. To elucidate the role of the cerebellar thalamus in humans, we studied a group of essential tremor (ET) patients with deep brain stimulation (DBS) electrodes placed in the cerebellar thalamus. The stimulation can be turned on or off remotely and is thought to reduce tremor by blocking the spread of the pathological output from the cerebellum. We studied the effect of thalamic DBS on the ability to adapt arm movements to novel force fields. Although thalamic DBS resulted in a dramatic and significant reduction of tremor in ET, it also impaired motor adaptation: the larger the stimulation voltage, the greater the reduction in rates of adaptation. We next examined ET patients that had undergone unilateral thalamotomy in the cerebellar thalamus and found that adaptation with the contralateral arm was impaired compared with the ipsilateral arm. Therefore, although both lesion and electrical stimulation of the cerebellar thalamus are highly effective in reducing tremor, they significantly impair the ability of the brain to form internal models of action. Adaptive control of reaching appears to depend on the integrity of the cerebello-thalamo-cortical pathway.

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

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.

Intraoperative microelectrode and semi-microelectrode recording during the physiological localization of the thalamic nucleus ventral intermediate.

We review the techniques of physiological localization of the site for ventralis intermedius (Vim) thalamotomy or implantation of Vim-deep brain stimulation (DBS) for treatment of parkinsonian, essential, and intention tremor. Both microelectrode and semi-microelectrode techniques are reviewed. We believe the use of microelectrode and semi-microelectrode recordings in combination with Radiological landmarks provide the most accurate localization of the target. In addition to recording, microstimulation of subcortical structures such as Vim and thalamic nucleus ventralis caudal through the microelectrode may improve physiological identification by altering the tremor and evoking somatic sensations, respectively. Microelectrode recording provides the highest resolution picture of the target site at a cost of increased time to locate the target. We also review the relationship between thalamic neuronal firing and electromyographic activity during tremor. Implications of these results for the mechanisms for parkinsonian, essential, and intention tremors are discussed.