Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders

Simone P. Haller*, Julia O. Linke, Hannah L. Grassie, Emily L. Jones, David Pagliaccio, Anita Harrewijn, Lauren K. White, Reut Naim, Rany Abend, Ajitha Mallidi, Erin Berman, Krystal M. Lewis, Katharina Kircanski, Nathan A. Fox, Wendy K. Silverman, Ned H. Kalin, Yair Bar-Haim, Melissa A. Brotman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objective: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT. Methods: Unmedicated youths diagnosed with an anxiety disorder underwent 12 weeks of CBT as part of two randomized clinical trials testing the efficacy of adjunctive computerized cognitive training. Across both trials, participants completed a threat-processing task during functional MRI before and after treatment. Age-matched healthy comparison youths completed two scans over the same time span. The mean age of the samples was 13.20 years (SD=2.68); 41% were male (youths with anxiety disorders, N=69; healthy comparison youths, N=62). An additional sample including youths at temperamental risk for anxiety (N=87; mean age, 10.51 years [SD=0.43]; 41% male) was utilized to test the stability of anxiety-related neural differences in the absence of treatment. Whole-brain regional activation changes (thresholded at p<0.001) were examined using task-based blood-oxygen-level-dependent response. Results: Before treatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy comparison children across all task conditions. Fronto-parietal hyperactivation normalized over the course of treatment, whereas limbic responses remained elevated after treatment. In the at-risk sample, overlapping clusters emerged between regions showing stable associations with anxiety over time and regions showing treatment-related changes. Conclusions: Activation in fronto-parietal networks may normalize after CBT in unmedicated pediatric anxiety patients. Limbic regions may be less amenable to acute CBT effects. Findings from the at-risk sample suggest that treatment-related changes may not be attributed solely to the passage of time.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalAmerican Journal of Psychiatry
Issue number3
StatePublished - Mar 2024


FundersFunder number
National Institute of Mental HealthZIAMH002781, NCT03283930, NCT00018057, ZIAMH002969


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