| Background. Subtle declines in episodic memory have been documented in individuals who have the CAG expansion for HD but have not reached the point of clinical diagnosis (pre-HD). Strategic aspects of episodic memory appear particularly vulnerable in pre-HD, and this has been attributed to neuropathology in the dorsal striatum that disrupts the dorsolateral prefrontal circuit. Recent evidence has also implicated the hippocampus and prefrontal cortex in HD, which are known to play vital roles in supporting episodic memory. It is unclear whether and to what extent these brain regions are affected in pre-HD and what, if any, role they play in the episodic memory dysfunction associated with the disease. This project examined the relationship between episodic memory and brain morphology in pre-HD. Method. The Hopkins Verbal Learning Test-Revised (HVLT-R; Brandt & Benedict, 2001) was administered to 72 individuals with the HD CAG expansion and 25 individuals who were at-risk for HD but tested negative for the genetic mutation. Volumetric measures of the dorsal striatum, hippocampus, and prefrontal cortex were obtained using magnetic resonance imaging (MRI). Analyses controlling for total intracranial volume, age, gender, and general intellectual function were used to assess for group differences in regional brain volumes and memory performance, and to examine brain-behavior relationships. Results. Dorsal striatal volumes were significantly smaller in the pre-HD group, whereas hippocampal and prefrontal cortex volumes did not differ between the groups. Episodic memory performance was poorer in the pre-HD group, and lower scores on the HVLT-R were associated with smaller dorsal striatal volumes and larger hippocampal volumes. In the control group, prefrontal cortex and dorsal striatal volumes were associated with measures of strategy use during episodic encoding and retrieval. Conclusions. Consistent with previous literature, these results implicate the dorsal striatum in episodic memory dysfunction in pre-HD, and also raise some interesting questions regarding the role of the hippocampus in the pre-HD episodic memory profile. Findings in the control group suggest that the dorsolateral prefrontal circuit, which involves projections from the prefrontal cortex to the dorsal striatum, may be an important component of the neural substrate for strategic memory. |
