ABSTRACT
BACKGROUND: Identifying stable and consistent resting-state functional connectivity patterns across illness trajectories has the potential to be considered fundamental to the pathophysiology of schizophrenia. We aimed to identify consistent resting-state functional connectivity patterns across heterogeneous schizophrenia groups defined based on treatment response. METHODS: In phase 1, we used a cross-sectional case-control design to characterize and compare stable independent component networks from resting-state functional magnetic resonance imaging scans of antipsychotic-naïve participants with first-episode schizophrenia (n = 54) and healthy participants (n = 43); we also examined associations with symptoms, cognition, and disability. In phase 2, we examined the stability (and replicability) of our phase 1 results in 4 groups (N = 105) representing a cross-sequential gradation of schizophrenia based on treatment response: risperidone responders, clozapine responders, clozapine nonresponders, and clozapine nonresponders following electroconvulsive therapy. Hypothesis-free whole-brain within- and between-network connectivity were examined. RESULTS: Phase 1 identified posterior and anterior cerebellar hypoconnectivity and limbic hyperconnectivity in schizophrenia at a familywise error rate-corrected cluster significance threshold of p < .01. These network aberrations had unique associations with positive symptoms, cognition, and disability. During phase 2, we replicated the phase 1 results while comparing each of the 4 schizophrenia groups to the healthy participants. The participants in 2 longitudinal subdatasets did not demonstrate a significant change in these network aberrations following risperidone or electroconvulsive therapy. Posterior cerebellar hypoconnectivity (with thalamus and cingulate) emerged as the most consistent finding; it was replicated across different stages of treatment response (Cohen's d range -0.95 to -1.44), reproduced using different preprocessing techniques, and not confounded by educational attainment. CONCLUSIONS: Posterior cerebellar-thalamo-cingulate hypoconnectivity is a consistent and stable state-independent neural marker of schizophrenia.
ABSTRACT
Processing advantages arising from self-association have been documented across various stimuli and paradigms. However, the implications of "self-association" for affective and social behavior have been scarcely investigated. The approach-avoidance task (AAT) offers an opportunity to investigate whether the privileged status of the "self" may also translate into differential evaluative attitudes toward the "self" in comparison to "others". In the current work, we first established shape-label associations using the associative-learning paradigm, and then asked the participants to engage in an approach-avoidance task to test whether attitudinal differences induced on the account of self-association lead to participants having different approach-avoidance tendencies toward the "self-related" stimuli relative to the "other-related" stimuli. We found that our participants responded with faster approach and slower avoidance tendencies for shapes associated with the "self" and slower approach and faster avoidance tendencies for the shapes associated with the "stranger." These results imply that "self-association" may lead to positive action tendencies toward "self-associated" stimuli, and at the same time lead to neutral or negative attitudes toward stimuli not related to the "self". Further, as the participants responded to self-associated vs. other-associated stimuli cohorts, these results may also have implications for the modulation of social group-behaviors in favor of those like the self and against those in contrast to the self-group.
