Abstract
BACKGROUND: Frontal-striatal dysfunction has been linked to cognitive impairment in Huntington's disease (HD). The frontal lobes play a role in memory for the temporal order in which items occur in a sequence. However, little is known about temporal order memory in HD or how it may be affected by interference. OBJECTIVE: The study assessed temporal order memory in patients with manifest HD (n = 20), premanifest gene carriers for HD (Pre-HD; n = 18), and controls (n = 25) using a computerized radial 8-arm maze. METHODS: On the sample phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two sample phase circles and chose the circle occurring earliest in the sequence. Manipulations of the temporal lag (defined as the number of circles occurring in the sample phase sequence between the two choice phase circles) were conducted to systematically vary interference. Temporally proximal lags were hypothesized to generate more interference relative to temporally distal lags. RESULTS: The Pre-HD group was significantly impaired (p < 0.05) compared to controls on proximal temporal lags (high interference) but matched controls on distal lags (low interference). HD patients improved as a function of increased lag but demonstrated significant impairments (p < 0.05) across lags relative to controls. CONCLUSIONS: Temporal order memory is differentially affected by interference during the premanifest and manifest stages of HD. The study identifies a fundamental, yet relatively unexamined, deficit associated with HD.