Abstract
BackgroundCognitive disturbances occur early in Huntington's disease (HD) and place a significant burden on the lives of patients and family members. Whilst these impairments are typically attributed to deterioration of the frontal-striatal pathways, accumulating evidence suggests that hippocampal dysfunction may also contribute to such impairments. Here, we employ a novel spatial memory task that has previously been shown to elicit impairments in individuals with focal hippocampal lesions, as a means to further investigate the role of hippocampal dysfunction in HD. MethodSixty-four individuals participated in the study, including 32 healthy controls, 11 patients with diagnosed HD and 16 premanifest HD gene carriers. We also included an additional control group of 5 individuals with focal unilateral basal ganglia lesions. Participants undertook a task that measured perception and short-term spatial memory using computer-generated visual scenes. ResultsHD patients experienced significant impairments in spatial perception and memory, which strongly correlated with disease burden score (DBS). Premanifest gene carriers performed at a similar level to healthy controls throughout all aspects of the task indicating that the effects seen in the HD patients represent a deterioration in function. Interestingly, basal ganglia lesion patients were not impaired in any aspects of the task. ConclusionThere is evidence of significant deficits in hippocampal-dependent spatial cognition in HD that cannot be explained as a function of degeneration to the basal ganglia. The impairments were greatest in individuals with higher DBSs, suggesting that deficits relate to the disease process in HD.
Highlights
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that typically develops in early to middle adulthood
Studies on the rodent hippocampal formation led to the seminal discovery of “place cells”, neurons that fire in relation to a rodent’s specific location within an environment regardless of its orientation [12]. These findings led to the suggestion that the hippocampus forms a so- called cognitive map of the spatial environment. Support for this idea comes from human studies which have demonstrated that damage to the hippocampus impairs spatial memory, primarily affecting allocentric rather than egocentric spatial processing [13,14] In addition, functional imaging studies have shown that the hippocampus is activated during spatial navigation of virtual environments (e.g. 15, 16) and that hippocampal volume correlates with navigational performance. [17,18, 19, 20]
No significant differences were found between controls, basal ganglia lesion patients and HD patients in terms of age and premorbid IQ
Summary
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that typically develops in early to middle adulthood. Studies on the rodent hippocampal formation led to the seminal discovery of “place cells”, neurons that fire in relation to a rodent’s specific location within an environment regardless of its orientation [12]. These findings led to the suggestion that the hippocampus forms a so- called cognitive map of the spatial environment. Cognitive disturbances occur early in Huntington’s disease (HD) and place a significant burden on the lives of patients and family members Whilst these impairments are typically attributed to deterioration of the frontal-striatal pathways, accumulating evidence suggests that hippocampal dysfunction may contribute to such impairments. The impairments were greatest in individuals with higher DBSs, suggesting that deficits relate to the disease process in HD
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