Huntington’s disease (HD) is an inherited brain disorder characterized by progressive motor, cognitive and behavioral dysfunctions. It is caused by abnormally large trinucleotide cytosine-adenine-guanine (CAG) repeat expansions on exon 1 of the Huntingtin gene. CAG repeat length (CAG-RL) inversely correlates with an earlier age of onset. Region-based studies have shown that Huntington’s disease gene mutation carriers (HDgmc) individuals (CAG-RL ≥ 36) present functional connectivity (FC) alterations in subcortical and default mode networks. In this analysis, we expand on previous HD studies by investigating associations between CAG-RL and connectivity in the whole brain, as well as between CAG dependent connectivity and motor and cognitive performances. We used group independent component analysis on resting-state fMRI scans of 261 individuals [183 HDgmc and 78 healthy controls (HC)] from the PREDICT-HD study, to obtain whole-brain resting state networks (RSNs). Regression analysis was applied within and between RSNs connectivity [functional network connectivity (FNC)] to identify CAG-RL associations. Results: Connectivity within the putamen RSN is negatively correlated with CAG-RL. The FNC between putamen and insula decreases with increasing CAG-RL, and also shows significant associations with motor and cognitive measures. The FNC between calcarine and middle frontal gyri increased with CAG-RL. In contrast, FNC in other visual networks declined with increasing CAG-RL. In addition to observed effects in subcortical areas known to be related to HD, our study identifies a strong presence of alterations in visual regions less commonly observed in previous reports and provides a step forward in understanding FNC dysfunction in HDgmc.

Background: Older African Americans are more likely to develop Alzheimer’s disease (AD) than older Caucasians, and this difference cannot be readily explained by cerebrovascular and socioeconomic factors alone. We previously showed that mild cognitive impairment and AD dementia were associated with attenuated increases in the cerebrospinal fluid (CSF) levels of total and phosphorylated tau in African Americans compared to Caucasians, even though there was no difference in beta-amyloid 1–42 level between the two races.Methods: We extended our work by analyzing early functional magnetic resonance imaging (fMRI) biomarkers of the default mode network in older African Americans and Caucasians. We calculated connectivity between nodes of the regions belonging to the various default mode network subsystems and correlated these imaging biomarkers with non-imaging biomarkers implicated in AD (CSF amyloid, total tau, and cognitive performance).Results: We found that race modifies the relationship between functional connectivity of default mode network subsystems and cognitive performance, tau, and amyloid levels.Conclusion: These findings provide further support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and identifies key inter-subsystem connections for deep imaging and neuropathologic characterization.

Clinical and experimental data have implicated the posterior superior temporal gyrus as an important cortical region in the processing of socially relevant stimuli such as gaze following, eye direction, and head orientation. Gaze following and responding to different socio-communicative signals is an important and highly adaptive skill in primates, including humans. Here, we examined whether individual differences in responding to socio-communicative cues was associated with variation in either grey matter volume and asymmetry in a sample of chimpanzees. MRI scans and behavioral data on receptive joint attention (RJA) was obtained from a sample of 191 chimpanzees. We found that chimpanzees that performed poorly on the RJA task had more rightward asymmetries in the posterior but not anterior superior temporal gyrus. We further found that middle-aged and elderly chimpanzee performed more poorly on the RJA task and had significantly less grey matter than young-adult and sub-adult chimpanzees. The results are consistent with previous studies implicating the posterior temporal gyrus in the processing of socially relevant information.

Objectives: Apathy is a debilitating symptom of Huntington’s disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington’s disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462–469)