Variable phenotype is common in neurological disorders with single-gene inheritance patterns. In Huntington's disease, mood and cognitive symptoms are variably co-expressed with motor symptoms. There is also variable degeneration of neurons in the two major neurochemical compartments of the striatum, the striosomes and the extrastriosomal matrix. To determine whether the phenotypic variability in Huntington's disease is related to this compartmental organization, we carried out a double-blind study in which we used GABA_A receptor immunohistochemistry to analyse the status of striosomes and matrix in the brains of 35 Huntington's disease cases and 13 control cases, and collected detailed data on the clinical symptomatology expressed by the patients from family members and records. We report here a significant association between pronounced mood dysfunction in Huntington's disease patients and differential loss of the GABA_A receptor marker in striosomes of the striatum. This association held for both clinical onset and end-stage assessments of symptoms. The cases with accentuated striosome abnormality further exhibited later onset age, lower disease grade and lower CAG repeat length in the HD gene. We found no independent association, however, between CAG repeat length or age of onset and mood dysfunction. We suggest that variation in clinical symptomatology in Huntington's disease is associated with variation in the relative abnormality of GABA_A receptor expression in the striosome and matrix compartments of the striatum, and that striosome-related circuits may modulate mood functioning.

Forty years have passed since video-games were first made widely available to the public and subsequently playing games has become a favourite past-time for many. Players continuously engage with dynamic visual displays with success contingent on the time-pressured deployment, and flexible allocation, of attention as well as precise bimanual movements. Evidence to date suggests that both brief and extensive exposure to video-game play can result in a broad range of enhancements to various cognitive faculties that generalize beyond the original context. Despite promise, video-game research is host to a number of methodological issues that require addressing before progress can be made in this area. Here an effort is made to consolidate the past 30 years of literature examining the effects of video-game play on cognitive faculties and, more recently, neural systems. Future work is required to identify the mechanism that allows the act of video-game play to generate such a broad range of generalized enhancements.

Just how expert are “expert” video-game players? Assessing the experience and expertise of video-game players across “action” video-game genres

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer’s dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer’s disease.