Connectivity between the central executive and salience networks normalizes with exposure-focused CBT in pediatric anxiety

Exposure is considered the most active element of cognitive behavioral therapy (CBT) for pediatric anxiety, and its efficacy is theorized to depend on cognitive control and its supporting neural substrates (e.g., central executive [CEN], salience [SN], and default mode networks [DMN]). However, little work has identified how CBT, or exposure specifically, modulates intrinsic connectivity of these networks. Progress may be limited by heterogeneity in network connectivity in anxiety, which may obscure treatment-related effects in group-averaged analyses. This randomized clinical trial (RCT) leverages person-specific network modeling to test how exposure-focused CBT (EF-CBT) influences resting-state connectivity of cognitive control networks in pediatric anxiety, relative to an active control (relaxation mentorship training; RMT). Youth aged 7-18 years with an anxiety disorder (N = 104) or low/no anxiety (L/NA; N = 37) completed resting-state fMRI scans before being randomized to EF-CBT or RMT. Resting-state connectivity was reassessed following treatment (or commensurate time L/NA youth) in 113 participants. Changes in within-CEN, CEN-SN, and CEN-DMN density were examined using Group Iterative Multiple Model Estimation, which yields sparse, person-specific networks capturing both shared and individual connectivity structure. At baseline, anxious youth exhibited lower density within-CEN, between CEN-SN, and between CEN-DMN than L/NA youth. Treatment effects differed by intervention: EF-CBT selectively increased (i.e., normalized) CEN-SN density, whereas RMT increased within-CEN density. These findings demonstrate dissociable effects of exposure and relaxation on cognitive control network organization in pediatric anxiety. Exposure-focused CBT uniquely strengthens coordination between control and salience systems, consistent with a mechanism supporting top-down control of threat-related signals during exposure. Network-based measures of cognitive control may help identify mechanistic targets for optimizing and personalizing treatment.

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Journal
medRxiv
Published
2026-01-30
DOI
https://doi.org/10.64898/2026.01.28.26345061
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Connectivity between the central executive and salience networks normalizes with exposure-focused CBT in pediatric anxiety

Hannah Becker, Christopher S. Monk, Stefanie Russman Block, Felicia A. Hardi et al.
medRxiv
Functional Brain Connectivity Studies
article

Connectivity between the central executive and salience networks normalizes with exposure-focused CBT in pediatric anxiety

Hannah Becker, Christopher S. Monk, Stefanie Russman Block, Felicia A. Hardi, Dana Diaz, Emily L. Bilek, Adriene M. Beltz, K. Luan Phan, Kate D Fitzgerald
article en

Abstract

Exposure is considered the most active element of cognitive behavioral therapy (CBT) for pediatric anxiety, and its efficacy is theorized to depend on cognitive control and its supporting neural substrates (e.g., central executive [CEN], salience [SN], and default mode networks [DMN]). However, little work has identified how CBT, or exposure specifically, modulates intrinsic connectivity of these networks. Progress may be limited by heterogeneity in network connectivity in anxiety, which may obscure treatment-related effects in group-averaged analyses. This randomized clinical trial (RCT) leverages person-specific network modeling to test how exposure-focused CBT (EF-CBT) influences resting-state connectivity of cognitive control networks in pediatric anxiety, relative to an active control (relaxation mentorship training; RMT). Youth aged 7-18 years with an anxiety disorder (N = 104) or low/no anxiety (L/NA; N = 37) completed resting-state fMRI scans before being randomized to EF-CBT or RMT. Resting-state connectivity was reassessed following treatment (or commensurate time L/NA youth) in 113 participants. Changes in within-CEN, CEN-SN, and CEN-DMN density were examined using Group Iterative Multiple Model Estimation, which yields sparse, person-specific networks capturing both shared and individual connectivity structure. At baseline, anxious youth exhibited lower density within-CEN, between CEN-SN, and between CEN-DMN than L/NA youth. Treatment effects differed by intervention: EF-CBT selectively increased (i.e., normalized) CEN-SN density, whereas RMT increased within-CEN density. These findings demonstrate dissociable effects of exposure and relaxation on cognitive control network organization in pediatric anxiety. Exposure-focused CBT uniquely strengthens coordination between control and salience systems, consistent with a mechanism supporting top-down control of threat-related signals during exposure. Network-based measures of cognitive control may help identify mechanistic targets for optimizing and personalizing treatment.

medRxiv
University of Michigan (US), Yale University (US), New York Psychoanalytic Society and Institute (US), New York State Psychiatric Institute, The Ohio State University (US), Columbia University (US)
National Institutes of Health, National Institute of Child Health and Human Development
Openalex Percentile: Top 72%
Functional Brain Connectivity Studies
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