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To improve the translational predictability of treatment strategies for Huntington's disease (HD), sensitive and analogous cognitive outcomes are needed across HD animal models and humans. Spatial memory measures are promising candidates because they are based on 'visual' or 'non-verbal' cognition, and are commonly tested in both animals and humans. Here, we consider the suitability of spatial memory for strengthening translational links between animals and humans in HD research and clinical trials. We describe findings of spatial memory impairments in human HD and mouse models, including which aspects of spatial memory are most affected and at which time points in disease progression. We also describe the neural systems that underlie spatial memory and link spatial memory impairments to HD neuropathology, focussing on striatal and hippocampal systems. We provide a critical analysis of the literature in terms of the suitability of spatial memory for bridging the translational gap between species. Finally, we discuss possible neural mechanisms that might explain the spatial memory impairments seen in HD, and their relevance to potential treatments.

Drug use is a choice with immediate positive outcomes, but long-term negative consequences. Thus, the repeated use of drugs in the face of negative consequences suggests dysfunction in the cognitive mechanisms underpinning decision-making. This cognitive dysfunction can be mapped into three stages: the formation of preferences involving valuation of decision options; choice implementation including motivation, self-regulation and inhibitory processes; and feedback processing implicating reinforcement learning. This article reviews behavioral studies that have examined alterations in these three stages of decision-making in people with substance use disorders. Relative to healthy individuals, those with alcohol, cannabis, stimulant and opioid use disorders value risky options more highly during the formation of preferences; have a greater appetite for superficially attractive rewards during choice implementation; and are both more efficient in learning from rewards and less efficient in learning from losses during feedback processing. These observed decision-making deficits are most likely due to both premorbid factors and drug-induced effects. Because decision-making deficits have been prospectively associated with a greater risk of drug relapse, we advocate for greater research on modulating the component stages that give rise to dysfunctional decision-making in disorders of addiction.

Emerging evidence suggests that autobiographical memory (ABM) is altered in Huntington's disease (HD). While these impairments are typically attributed to frontostriatal dysfunction, the neural substrates of ABM impairment in HD remain unexplored. To this end, we assessed ABM in 30 participants with genetically confirmed HD (18 premanifest, 12 manifest) and 24 age‐matched healthy controls. Participants completed the Autobiographical Interview to assess free and probed ABM recall and underwent structural brain imaging. Whole‐brain voxel‐based morphometry (VBM) was used to explore voxel‐wise associations between ABM performance and grey matter intensity (False Discovery Rate corrected at q = 0.05). Relative to controls, HD participants displayed significantly less detailed ABM retrieval across free and probed recall conditions, irrespective of disease stage. Recall performance did not differ significantly between manifest and premanifest HD groups. VBM analyses indicated that poorer ABM performance was associated with atrophy of a distributed cortico‐subcortical network. Key regions implicated irrespective of ABM condition included the bilateral occipital cortex, left precuneus, right parahippocampal gyrus and right caudate nucleus. In addition, probed ABM recall was associated with the superior and inferior frontal gyri, frontal pole, right hippocampus, nucleus accumbens, paracingulate gyrus and cerebellum. Overall, our findings indicate that ABM impairments in HD reflect the progressive degeneration of a distributed cortico‐subcortical brain network comprising medial temporal, frontal, striatal and posterior parietal cortices. Our findings advance our understanding of the neurocognitive profile of HD, providing an important foundation for future interventions to support memory function in this population. [ABSTRACT FROM AUTHOR]

We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected Part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with Part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with Part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9-15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.

Objective: Neuropsychological evaluation is critical to detection and management of cognitive and neuropsychiatric changes associated with Huntington disease (HD). Accurate assessment of non-motor complications of HD is critical given the prominent impact on functional disability, frequently commensurate with or exceeding that of motor symptoms. The increasing emphasis on developing disease-modifying therapies targeting cognitive decline in HD requires consensus on clinical neuropsychological assessment methods. The Neuropsychology Working Group (NPWG) of the Huntington Study Group (HSG) sought to provide evidence and consensus-based, practical guidelines for the evaluation of cognitive and neuropsychiatric symptoms associated with HD. Method: The NPWG recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to inform best practices in assessing, diagnosing, and treating the non-motor symptoms in HD. A review was circulated among the NPWG, and in an iterative process informed by reviewed literature, best practices in neuropsychological evaluation of patients with HD were identified. Results: A brief review of the available literature and rational for a clinical consensus battery is offered. Conclusion: Clinical neuropsychologists are uniquely positioned to both detect and characterize the non-motor symptoms in HD, and further, provide neurologists and allied health professions with clinically meaningful information that impacts functional outcomes and quality of life. The NPWG provides guidance on best practices to clinical neuropsychologists in this statement. A companion paper operationalizing clinical application of previous research-based non-motor diagnostic criteria for HD is forthcoming, which also advises on non-motor symptom screening methods for the non-neuropsychologist working with HD. [ABSTRACT FROM AUTHOR]