%0 Journal Article
%T Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome.
%A Ward HB
%A Beermann A
%A Xie J
%A Yildiz G
%A Felix KM
%A Addington J
%A Bearden CE
%A Cadenhead K
%A Cannon TD
%A Cornblatt B
%A Keshavan M
%A Mathalon D
%A Perkins DO
%A Seidman L
%A Stone WS
%A Tsuang MT
%A Walker EF
%A Woods S
%A Coleman MJ
%A Bouix S
%A Holt DJ
%A Öngür D
%A Breier A
%A Shenton ME
%A Heckers S
%A Halko MA
%A Lewandowski KE
%A Brady RO
%J Biol Psychiatry
%V 0
%N 0
%D 2024 Jul 18
%M 39032726
%F 12.81
%R 10.1016/j.biopsych.2024.07.012
%X <B>BACKGROUND: </B>Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future.<BR><B>METHODS: </B>The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants.<BR><B>RESULTS: </B>Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132).<BR><B>CONCLUSIONS: </B>This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.