No abstract

Introduction Huntington’s disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). Methods As part of the PREDICT-HD study, N =191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1–5 year follow-up) DWI, with n =649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. Results Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. Conclusions This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the pre-motor area and the putamen, which may be closely tied to the onset of motor symptoms in HD.

Background: The negative symptoms of schizophrenia include deficits in emotional expression and motivation. These deficits are stable over the course of illness and respond poorly to current medications. Previous studies have focused on negative symptoms as a single category; however, individual symptoms might be related to separate neurological disturbances. We analyzed data from the Functional Biomedical Informatics Research Network dataset to explore the relationship between individual negative symptoms and functional brain activity during an auditory oddball task. Methods: Functional magnetic resonance imaging was conducted on 89 schizophrenia patients and 106 healthy controls during a two-tone auditory oddball task. Blood oxygenation level-dependent (BOLD) signal during the target tone was correlated with severity of five negative symptom domains from the Scale for the Assessment of Negative Symptoms. Results: The severity of alogia, avolition/apathy and anhedonia/asociality was negatively correlated with BOLD activity in distinct sets of brain regions associated with processing of the target tone, including basal ganglia, thalamus, insular cortex, prefrontal cortex, posterior cingulate and parietal cortex. Conclusions: Individual symptoms were related to different patterns of functional activation during the oddball task, suggesting that individual symptoms might arise from distinct neural mechanisms. This work has potential to inform interventions that target these symptom-related neural disruptions.

Bipolar disorder is characterized by recurring episodes of depression and mania. Defining differences in brain function during these states is an important goal of bipolar disorder research. However, few imaging studies have directly compared brain activity between bipolar mood states. Herein, we compare functional magnetic resonance imaging (fMRI) responses during a flashing checkerboard stimulus between bipolar participants across mood states (euthymia, depression, and mania) in order to identify functional differences between these states. 40 participants with bipolar I disorder and 33 healthy controls underwent fMRI during the presentation of the stimulus. A total of 23 euthymic-state, 16 manic-state, 15 depressed-state, and 32 healthy control imaging sessions were analyzed in order to compare functional activation during the stimulus between mood states and with healthy controls. A reduced response was identified in the visual cortex in both the depressed and manic groups compared to euthymic and healthy participants. Functional differences between bipolar mood states were also observed in the cerebellum, thalamus, striatum, and hippocampus. Functional differences between mood states occurred in several brain regions involved in visual and other sensory processing. These differences suggest that altered visual processing may be a feature of mood states in bipolar disorder. The key limitations of this study are modest mood-state group size and the limited temporal resolution of fMRI which prevents the segregation of primary visual activity from regulatory feedback mechanisms.