Connectome-Wide Analysis Identifies Treatment Targets for Cognitive Impairment in Individuals at Clinical High Risk for Psychosis

Heather Ward, MD

Beth Israel Deaconess Medical Center – Fellow
Ward_Heather poster

Scientific Abstract

Background: Neurocognitive impairment is a well-known phenomenon in schizophrenia which has also been observed during the clinical high risk (CHR) period of psychosis. Almost all cognitive impairment occurs prior to the development of psychosis, so identifying targets during the at-risk period is critical. Analyses of traditional cognitive tasks have identified inconsistent biological links to cognitive deficits and have often been confined to a priori hypotheses. We therefore conducted a connectome-wide analysis to identify CHR-specific circuits of cognitive performance.

Methods: We analyzed data from the North American Prodrome Longitudinal Study, a multi-site prospective study where 213 CHR individuals and 132 controls underwent resting-state fMRI and clinical characterization. A multivariate pattern analysis of whole-connectome data was used to identify the strongest links between cognitive performance on an auditory task designed specifically for psychotic disorders (Auditory Continuous Performance Task, ACPT) compared to traditional cognitive tasks (CPT – Identical Pairs, Wechsler Memory Scale Spatial Span).

Results: The auditory task specialized to psychotic disorders gave rise to robust brain-cognition links that were not seen with traditional tasks. Functional connectivity was significantly related to performance on all 3 measures of the ACPT (Vigilance, Memory, Interference) only in CHR individuals (ps<.005). ACPT Vigilance was related to insula connectivity to the task-positive network (TPN). ACPT Memory was related to parieto-occipital connectivity to the default mode network. ACPT Interference was related to putamen connectivity to the TPN. The connectivity relationships observed in the CHR sample were even stronger in converters.

Conclusions: In this data-driven, connectome-wide analysis, we identified novel links between brain networks and cognitive performance in CHR individuals, even before a schizophrenia diagnosis, using an auditory task specifically designed for psychotic disorders. The ACPT may be critical for identification of brain network targets of impaired cognition in the CHR period, which can be engaged using non-invasive neuromodulation.


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research Areas


Heather Burrell Ward, MD, Adam Beermann, MA, Jing Xie, BA, Gulcan Yildiz, MD, Jean Addington, PhD­­­, Carrie Bearden, PhD­­­, Kristin Cadenhead, MD­­­, Tyrone D. Cannon, PhD­­­, Barbara Cornblatt, PhD, MBA­­­, Daniel Mathalon, MD, PhD­­­, Thomas McGlashan, MD­­­, Diana O. Perkins, MD, MPH­­­, Larry Seidman, PhD­­­, William S. Stone, PhD­­­, Ming T. Tsuang, MD, PhD, DSc, Elaine F. Walker, PhD­­­, Scott Woods, MD­­­, Mark A. Halko, PhD, Kathryn E. Lewandowski, PhD, Roscoe O. Brady, Jr., MD, PhD

Principal Investigator

Roscoe O. Brady, Jr. MD, PhD

Affiliated Website