All patients were operated more than five years after the diagnosis. None of the patients with essential tremor had a preexisting cerebellar injury on the basis of history, neurological examination, and brain imaging as reviewed with a neuroradiologist. None of the patients with cerebellar tremor had any family or personal history of essential tremor or any symptoms of tremor before their cerebellar injury. The control group consisted of patients

with neuropathic lower extremity pain. None of them had a personal or family history of tremor. They had no cerebral or cerebellar pathology based on detailed neurological examination and MRI imaging. Their electrophysiological recordings were therefore suitable selleck chemicals to use a control for comparison of firing rates and other parameters with the tremor patients. The protocol was reviewed and approved annually by the Institutional Review Board of the Johns Hopkins University. All

patients signed an informed consent for these studies. Details of the methods used in this study have been previously described (Hua and Lenz, 2005). Thalamic exploration was performed as a stereotactic procedure using the Leksell frame in patients who were off tremor medications for at least 18 h. First, the frame coordinates of the anterior (AC) and posterior commissures (PC, Fig. 1A) were measured by magnetic resonance imaging (MRI) or computed tomography. These coordinates were used to estimate the nuclear locations. selleck chemicals llc Physiological corroboration of nuclear location was then performed under local anesthesia without sedation (i.e. subject fully conscious) by single unit recording and microstimulation through a microelectrode. We used a platinum–iridium electrode etched to

a tip of 3–4 mm and coated with solder glass to give an impedance of approximately 2.5 MΩ, which was reduced to approximately 5 MΩ by microstimulation (50 µA) in the brain. The electrode was advanced toward the target as localized by pre-operative imaging. The signals recorded on magnetic tape (Model 4000, Vetter Corp., Rebersberg, PA, USA) or electronically (Cambridge Electronic Design, CED PIK-5 1401 interface) during the procedure included: the foot pedal indicating events during the examination, the microelectrode signal, electromyogram (EMG) for wrist flexors and extensors plus elbow flexors and extensors in the contralateral upper limb, the audio channel describing instructions to the patient as well as technical details of the procedure. The physiological exploration with the microelectrode involved both the recording of neuronal activity and stimulating at microampere current levels. When a neuron was isolated, spontaneous activity was recorded. The activity of the isolated neuron was then studied to identify neurons responding to cutaneous stimuli such as light touch, tapping or pressure to skin.