Temporal order memory dysfunction in Huntington's diseases

Title from first page of PDF file (viewed January 3, 2011)Includes bibliographical references (p. 31-40)Huntington's disease (HD) is a genetically inherited neurological condition marked by motor, cognitive, and behavioral disturbances. The identification of novel indicators of disease progression are important for the diagnosis and assessment of HD. Findings from previous studies involving humans and animals with lesions in the frontal cortex suggest that the frontal lobes play a major role in memory for the temporal order of sequences of events. Since HD results in damage to the frontostriatal circuits, temporal order memory may be particularly sensitive to neuropathological degeneration in HD and may serve as a cognitive marker of disease progression. In the present study, HD patients and normal controls were administered a visuospatial temporal order memory task on a computerized radial eight-arm maze. On the study phase of each trial, participants were presented with a random sequence of circles shown one at a time at the end of each of the eight arms. On the choice phase, participants were presented with a circle at the end of two of the study phase arms and were asked to choose the circle that occurred earliest in the sequence. In order to vary temporal interference, parametric manipulations of the temporal metric were carried out by systematically changing the temporal separation lag between the two circles in the choice phase. Prior research demonstrates that temporal order memory is superior for items occurring further apart in a sequence than items that are temporally closer in time. This temporal lag effect is assumed to occur because there is greater temporal interference between temporally proximal items in a sequence than temporally distal items. The data indicated that HD patients were significantly impaired on the temporal order memory task compared to controls. The data also revealed that overall performance improved as temporal separation lag increased. Normal controls outperformed HD patients on the 0, 4, and 6 temporal separation lag trials; however, there were no significant between group differences on the 2 temporal separation lag trials. These results indicate that temporal order memory is impaired in HD patients even when temporal interference is minimal. The present findings, combined with a previously published study from our lab, suggest that temporal order memory tasks may serve as an early marker of phenoconversion to manifest HD and a useful measure of disease progression