Fronto-striatal circuits for cognitive flexibility in far from onset Huntington's disease: evidence from the Young Adult Study.

OBJECTIVES: Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest Huntington's disease (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists and if so, whether fronto-striatal circuits were associated with this deficit. METHODS: In the present study, we examined performance of 51 pre-HD participants (mean age=29.22 (SD=5.71) years) from the HD Young Adult Study cohort and 53 controls matched for age, sex and IQ, on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set-Shift (IED) task. This cohort is unique as it is the furthest from disease onset comprehensively studied to date (mean years=23.89 (SD=5.96) years). The IED task measures visual discrimination learning, cognitive flexibility and specifically attentional set-shifting. We used resting-state functional MRI to examine whether the functional connectivity between specific fronto-striatal circuits was dysfunctional in pre-HD, compared with controls, and whether these circuits were associated with performance on the critical extradimensional shift stage. RESULTS: Our results demonstrated that the CANTAB IED task detects a mild early impairment in cognitive flexibility in a pre-HD group far from onset. Attentional set-shifting was significantly related to functional connectivity between the ventrolateral PFC and ventral striatum in healthy controls and to functional connectivity between the dorsolateral PFC and caudate in pre-HD participants. CONCLUSION: We postulate that this incipient impairment of cognitive flexibility may be associated with intrinsically abnormal functional connectivity of fronto-striatal circuitry in pre-HD

Empathy in youths: Change in patterns of eye gaze and brain activity with the manipulation of visual attention to emotional faces

Background & aim: Understanding the emotional state of others is fundamental to effective social interaction and the development of empathy. Critical information is conveyed via the eyes, and reduced attention to the eyes is associated with poorer emotion recognition and empathic deficits in individuals with disorders affecting social cognition such as autism or some types of conduct problems. Deliberately redirecting attention to the eyes may be a way of improving behaviour. However, the effects of directing attention on brain activity during emotional processing has not been studied previously. Our aim was to determine whether manipulation of visual attention in youths affects their eye gaze patterns and brain responses to expression of emotions in others. Method: Eighteen typically developing male youths aged 8-16 performed an implicit facial emotion processing task while viewing different facial expressions (fearful, neutral, happy), presented in three separate blocks under three different instructions: undirected, eye-gaze and mouth-gaze. Eye tracking (dwell time) and functional-MRI data were acquired concurrently as measures of visual attention and brain response, respectively. Results: Eye tracking indicated that the youths attended more to the eyes than the mouth in the undirected condition. Redirecting attention to the eyes and mouth significantly increased attention to these areas. Compared to undirected, directing attention to the fearful eyes also produced a greater increase in attention than neutral eyes. Attention directed to eyes elicited greater brain activity in frontal regions than undirected attention. Discussion & conclusions: The undirected eye gaze patterns indicate natural orienting to eyes in healthy youths, which can be effectively altered with instruction. Directing attention to fearful eyes engaged attention relatively longer than neutral, consistent with the threat value of fearful faces. These data also demonstrate that manipulation of visual attention modulates activity in frontal regions, perhaps reflecting greater engagement of executive function due to attentional demands. Understanding attentional manipulation effects in a healthy sample will inform ongoing work addressing potentially perturbed response patterns in a conduct problem cohort