Objective: To better understand the mechanism underlying cognitive impairment in HD.

Background: Cognitive impairment can precede the motor symptoms and deteriorates over time in HD patients. Functional MRI (fMRI) provides new insight into the pathologic mechanism underlying the cognitive impairment. Previous fMRI studies on HD focused on functional synchronization of various brain areas via measuring resting-state functional connectivity, a method unable to identify intrinsic neural activity changes in individual brain structures. To fill in this gap, we adopted Amplitude of low frequency fluctuations (ALFF), which has proven to be a reliable index of intrinsic brain activity.

Methods: Ten HD patients in early stage and 20 age- and sex- matched healthy controls (HC) received resting-state MRI brain scans. HD patients were evaluated by Unified Huntington’s Disease Rating Scale (UHDRS), Stroop test and Symbol Digit Modality Test (SDMT). Voxel-based morphometry of the T1 sequences was applied to detect brain volume reduction. Mean ALFF of the functional sequences was calculated using the REST software and compared between HD and HC groups, adjusted for gray matter volume. Pearson correlation analysis was conducted between clinical scores and ALFF values extracted from the abnormal areas in HD.

Results: Brain volume reduction was detected in the bilateral striatum and left calcarine cortex in the HD group (p<0.05,FWE corrected). HD patients demonstrated significantly decreased ALFF in the bilateral precuneus and right angular gyrus (right AG), whereas increased ALFF in the bilateral inferior temporal gyrus (ITG) and the left superior frontal gyrus (left SFG) (all ps<0.05,corrected by AlphaSim program), adjusted for gray matter volume. ALFF in the left ITG was negatively correlated with SDMT score (r=-0.697, p=0.025). ALFF in the precuneus was positively correlated with performance in the Stroop test (r=0.784,p=0.007) and SDMT (r=0.740,p=0.014).

Conclusions: Intrinsic brain activity in the precuneus, right AG, ITG and left SFG is altered in HD. Furthermore, the precuneus and left ITG correlate with cognitive performance, suggesting that intrinsic brain activity changes in these two areas may be unique mechanism underlying impaired cognition in early HD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/abnormal-intrinsic-brain-activity-reveals-neural-correlates-of-impaired-cognitive-function-in-early-stage-of-huntingtons-disease-hd-a-resting-state-fmri-study/