Preparatory modulation of intrinsic neural activity among psychotic illnesses
Hudgens-Haney, Matthew Eldridge
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Deviations in intrinsic, or nonspecific, neural activity have been proposed as a genetically-mediated core deficit in cortical functioning in psychosis. Levels of ongoing, non-specific activity are likely more proximal to gene transcription than either behavioral or clinical measures and could possibly provide an objective, easily quantifiable index of liability for developing a full-blown psychosis. Individuals with psychosis often show high levels of intrinsic, or nonspecific, neural activity, but attenuated stimulus-specific activity. Clementz et al. (2016) proposed that one subgroup of psychosis cases has accentuated intrinsic activity (Biotype-2’s) and a different subgroup (Biotype-1’s) has diminished intrinsic activity, with both groups exhibiting varying degrees of cognitive deficits. The present set of investigations sought to (i) examine differences in intrinsic neural activity between psychosis subgroups, (ii) understand the relationship between intrinsic activity and modulation of this activity in psychosis, and (iii) to assess the utility of these brain measures as potential endophenotypes. These studies assessed neural activity during baseline and a 5 sec period in preparation for a pro-anti-saccade task. The use of steady-state stimuli allowed real-time assessment of modulation of visuocortical investment in relation to either central fixation or peripheral target locations. Sensory responsiveness and neural modulation abilities were evaluated as a function of subgrouping psychosis cases by clinical versus neurobiological features. The sum of the results indicates that differences in intrinsic neural activity are likely to be a fundamental characteristic of psychosis. These abnormalities discriminate psychosis subgroups in ways that cannot accounted for by either behavior or clinical symptoms. Further, similar deviations are observed in unaffected relatives and show moderate to high levels of heritability, providing support for future research on their utility as endophenotypes for psychosis. The modulation of intrinsic activity as a function of cognitive demands also shows promise as a topic for continued study. Psychosis Biotypes differed from one another in how overall levels of intrinsic activity were adjusted between conditions of cognitive simplicity (prosaccade blocks) versus complexity (antisaccade blocks). While stimulus-specific modulations showed trend-level differences in probands, these modulations revealed complex differences between unaffected relatives, providing clues toward potential compensatory mechanisms.