Faculty Collaboration Database

Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach. Biol Psychiatry Cogn Neurosci Neuroimaging 2022 Feb;7(2):139-149

Date

09/04/2021

Pubmed ID

34478884

Pubmed Central ID

PMC8825698

DOI

10.1016/j.bpsc.2021.08.007

Scopus ID

2-s2.0-85118738043 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

BACKGROUND: Posttraumatic stress disorder (PTSD) is a debilitating disorder, and there is no current accurate prediction of who develops it after trauma. Neurobiologically, individuals with chronic PTSD exhibit aberrant resting-state functional connectivity (rsFC) between the hippocampus and other brain regions (e.g., amygdala, prefrontal cortex, posterior cingulate), and these aberrations correlate with severity of illness. Previous small-scale research (n < 25) has also shown that hippocampal rsFC measured acutely after trauma is predictive of future severity using a region-of-interest-based approach. While this is a promising biomarker, to date, no study has used a data-driven approach to test whole-brain hippocampal FC patterns in forecasting the development of PTSD symptoms.

METHODS: A total of 98 adults at risk of PTSD were recruited from the emergency department after traumatic injury and completed resting-state functional magnetic resonance imaging (8 min) within 1 month; 6 months later, they completed the Clinician-Administered PTSD Scale for DSM-5 for assessment of PTSD symptom severity. Whole-brain rsFC values with bilateral hippocampi were extracted (using CONN) and used in a machine learning kernel ridge regression analysis (PRoNTo); a k-folds (k = 10) and 70/30 testing versus training split approach were used for cross-validation (1000 iterations to bootstrap confidence intervals for significance values).

RESULTS: Acute hippocampal rsFC significantly predicted Clinician-Administered PTSD Scale for DSM-5 scores at 6 months (r = 0.30, p = .006; mean squared error = 120.58, p = .006; R² = 0.09, p = .025). In post hoc analyses, hippocampal rsFC remained significant after controlling for demographics, PTSD symptoms at baseline, and depression, anxiety, and stress severity at 6 months (B = 0.59, SE = 0.20, p = .003).

CONCLUSIONS: Findings suggest that functional connectivity of the hippocampus across the brain acutely after traumatic injury is associated with prospective PTSD symptom severity.

Author List

Fitzgerald JM, Webb EK, Weis CN, Huggins AA, Bennett KP, Miskovich TA, Krukowski JL, deRoon-Cassini TA, Larson CL

Authors

Carissa W. Tomas PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Terri A. deRoon Cassini PhD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Brain
Hippocampus
Humans
Magnetic Resonance Imaging
Prospective Studies
Stress Disorders, Post-Traumatic