BackgroundCognitive and motor task performance in premanifest Huntington's disease (HD) gene-carriers is often within normal ranges prior to clinical diagnosis, despite loss of brain volume in regions involved in these tasks. This indicates ongoing compensation, with the brain maintaining function in the presence of neuronal loss. However, thus far, compensatory processes in HD have not been modeled explicitly. Using a new model, which incorporates individual variability related to structural change and behavior, we sought to identify functional correlates of compensation in premanifest-HD gene-carriers.MethodsWe investigated the modulatory effects of regional brain atrophy, indexed by structural measures of disease load, on the relationship between performance and brain activity (or connectivity) using task-based and resting-state functional MRI.FindingsConsistent with compensation, as atrophy increased performance-related activity increased in the right parietal cortex during a working memory task. Similarly, increased functional coupling between the right dorsolateral prefrontal cortex and a left hemisphere network in the resting-state predicted better cognitive performance as atrophy increased. Such patterns were not detectable for the left hemisphere or for motor tasks.InterpretationOur findings provide evidence for active compensatory processes in premanifest-HD for cognitive demands and suggest a higher vulnerability of the left hemisphere to the effects of regional atrophy.

Diagnostic features of emotional expressions are differentially distributed across the face. The current study examined whether these diagnostic features are preferentially attended to even when they are irrelevant for the task at hand or when faces appear at different locations in the visual field. To this aim, fearful, happy and neutral faces were presented to healthy individuals in two experiments while measuring eye movements. In Experiment 1, participants had to accomplish an emotion classification, a gender discrimination or a passive viewing task. To differentiate fast, potentially reflexive, eye movements from a more elaborate scanning of faces, stimuli were either presented for 150 or 2000 ms. In Experiment 2, similar faces were presented at different spatial positions to rule out the possibility that eye movements only reflect a general bias for certain visual field locations. In both experiments, participants fixated the eye region much longer than any other region in the face. Furthermore, the eye region was attended to more pronouncedly when fearful or neutral faces were shown whereas more attention was directed toward the mouth of happy facial expressions. Since these results were similar across the other experimental manipulations, they indicate that diagnostic features of emotional expressions are preferentially processed irrespective of task demands and spatial locations. Saliency analyses revealed that a computational model of bottom-up visual attention could not explain these results. Furthermore, as these gaze preferences were evident very early after stimulus onset and occurred even when saccades did not allow for extracting further information from these stimuli, they may reflect a preattentive mechanism that automatically detects relevant facial features in the visual field and facilitates the orientation of attention towards them. This mechanism might crucially depend on amygdala functioning and it is potentially impaired in a number of clinical conditions such as autism or social anxiety disorders.

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In pre-clinical Huntington's disease, normal behaviour is maintained despite neurodegeneration, suggesting a mechanism of compensation. Gregory, Long et al. present two mathematical models of compensation over time and their operationalisation for neuroimaging.