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.

Cognitive factors underpinning poor expressive communication skills after traumatic brain injury: theory of mind or executive function?

OBJECTIVE: The ability to see things from another's perspective, that is, have a theory of mind (ToM), is essential to effective communication. So too is the ability to regulate verbal output, that is, to exercise executive control. People with traumatic brain injuries (TBIs) have impaired communication abilities, but the extent to which this reflects ToM versus executive dysfunction is unclear. This study explored the relative contributions of executive abilities, specifically flexibility and inhibition and ToM abilities in language production post-TBI. METHOD: Twenty-five adults (18 males: mean age of 48.2 years, SD = 12.0 years) with moderate to severe TBI (posttraumatic amnesia = 69.2, SD = 54.6 days) and 28 noninjured adults (19 males: mean age 49.0, SD = 12.2 years) completed three sets of communication tasks with low executive demands, high flexibility, and high inhibition demands. Within each, parallel versions had low or high ToM requirements. RESULTS: For low executive and high flexibility tasks, scores on the high ToM versions were predicted by scores on the low ToM versions, suggesting that poor performance was explained by the executive demands the parallel tasks had in common. The exception was the high inhibition task. In this case, speakers with TBI had differential difficulty with the high ToM version, that is, they had specific difficulty inhibiting self-referential thoughts in order to cater for another's perspective. CONCLUSION: We found problems with inhibiting the self-perspective accords with descriptive accounts of the egocentric nature of some communication patterns following TBI, which points to potential targets for remediation.