Pallidal neuronal discharge in Huntington's disease: Support for selective loss of striatal cells originating the indirect pathway

Abstract

Chorea is the predominant motor manifestation in the early symptomatic phase of adult onset Huntington's disease (HD). Pathologically, this stage is marked by differential loss of striatal neurons contributing to the indirect pathway. This pattern of neuronal loss predicts decreased neuronal firing rates in GPi and increased firing rates in GPe, the opposite of the changes in firing rate known to occur in Parkinson's disease (PD). We present single-unit discharge characteristics (33 neurons) observed in an awake patient with HD (41 CAG repeats) undergoing microelectrode guided surgery for pallidal deep brain stimulation. Pallidal single-unit activity at “rest” and during voluntary movement was discriminated off line by principal component analysis and evaluated with respect to discharge rate, bursting, and oscillatory activity in the 0–200 Hz range. 24 GPi and 9 GPe units were studied, and compared with 132 GPi and 50 GPe units from 14 patients with PD. The mean (+/− SEM) spontaneous discharge rate for HD was 58 +/− 4 for GPi and 73 +/− 5 for GPe. This contrasted with discharge rates in PD of 95 +/− 2 for GPi and 57 +/− 3 for GPe. HD GPi units showed more bursting than PD GPi units but much less oscillatory activity in the 2–35 Hz frequency range at rest. These findings are consistent with selective early loss of striatal cells originating the indirect pathway.