Eight patients with medically refractory disabling essential tremor underwent ventralis lateralis (VL) thalamotomies; the procedure was unilateral in seven cases and bilateral (staged) in the other. Contralateral tremor remained absent or markedly reduced in all patients at the time of the most recent follow-up examinations, at a mean of 17.3 months after surgery. Disability was determined by a modified form of an established rating scale for tremor, and was reduced from a mean score of 21.1 (moderate grade) to 3.9 (absent grade) (p less than 0.001). Interestingly, voice tremor was abolished or significantly improved in 71.4% of patients with preoperative voice tremor. This feature has not been reported previously. Persistent surgical morbidity was limited to two patients with mild dysarthria and one with a mild cognitive impairment. There were no surgically related deaths. It is concluded that stereotactic VL thalamotomy is a treatment option for medically intractable disabling essential tremor.

How are actions linked with subsequent outcomes to guide choices? The nucleus accumbens (NAc), which is implicated in this process, receives glutamatergic inputs from the prelimbic cortex (PL) and midline regions of the thalamus (mTH). However, little is known about what is represented in PL or mTH neurons that project to NAc (PL-NAc and mTH-NAc). By comparing these inputs during a reinforcement learning task in mice, we discovered that i) PL-NAc preferentially represents actions and choices, ii) mTH-NAc preferentially represents cues, iii) choice-selective activity in PL-NAc is organized in sequences that persist beyond the outcome. Through computational modeling, we demonstrate that these sequences can support the neural implementation of temporal difference learning, a powerful algorithm to connect actions and outcomes across time. Finally, we test and confirm predictions of our circuit model by direct manipulation of PL-NAc neurons. Thus, we integrate experiment and modeling to suggest a neural solution for credit assignment.

A fundamental principle of biological motor control is that the neural commands driving movement must conform to the response properties of the motor plants they control. In the oculomotor system, characterizations of oculomotor plant dynamics traditionally supported models in which the plant responds to neural drive to extraocular muscles on exclusively short, subsecond timescales. These models predict that the stabilization of gaze during fixations between saccades requires neural drive that approximates eye position on longer timescales and is generated through the temporal integration of brief eye velocity-encoding signals that cause saccades. However, recent measurements of oculomotor plant behaviour have revealed responses on longer timescales, and measurements of firing patterns in the oculomotor integrator have revealed a more complex encoding of eye movement dynamics. Here we use measurements from new and published experiments in the larval zebrafish to link dynamics in the oculomotor plant to dynamics in the neural integrator. The oculomotor plant in both anaesthetized and awake larval zebrafish was characterized by a broad distribution of response timescales, including those much longer than one second. Analysis of the firing patterns of oculomotor integrator neurons, which exhibited a broadly distributed range of decay time constants, demonstrates the sufficiency of this activity for stabilizing gaze given an oculomotor plant with distributed response timescales. This work suggests that leaky integration on multiple, distributed timescales by the oculomotor integrator reflects an inverse model for generating oculomotor commands, and that multi-timescale dynamics may be a general feature of motor circuitry.