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Working Paper

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Apathy is a symptom of many neurodegenerative and neuropsychiatric disorders, such as Huntington's disease and schizophrenia. Apathy is often conceptualized as a combination of three domains, cognitive, behavioral, and emotional, characterized by impaired goal-directed behavior. The striatum has been shown to be significantly associated with executive functions and planned motor behavior via projection to the prefrontal cortex (PFC). Due to its connection to the PFC and its involvement in the basal ganglia motor circuit, the striatum is thought to be a significant part of the circuit that controls goal-directed behavior. The purpose of this study was to investigate the relationship between apathy severity and dorsal striatal grey matter concentration across several disorders, specifically Huntington's disease and schizophrenia. With access to the PREDICT-HD and FBIRN datasets, structural MRI images and clinical assessments were collected from 823 and 178 participants, respectively. We employed the use of SBM to isolate relevant basal ganglia components and used the resulting loading coefficients for a multivariate analysis. In parallel, we also conducted a univariate analysis using segmented subcortical volumetric data. We then constructed a mixed linear model to examine the relationship between apathy and any gray matter patterns in the striatum. In Huntington’s disease, our results indicate that apathy is significantly related to the caudate and putamen atrophy with covarying in the medial PFC. In schizophrenia, our results indicate that apathy is significantly related to the putamen with covarying regions in the gyrus rectus and orbital medial PFC. We concluded that Huntington’s disease and schizophrenia manifest apathy in different ways in unique structures.