Examining Anterior Prefrontal Cortex Resting-State Functional Connectivity Patterns Associated with Depressive Symptoms in Chronic Moderate-to-Severe Traumatic Brain Injury

Layan A. Elfaki ^1,2* Bhanu Sharma ³ Liesel-Ann C. Meusel ² Isis So ⁴ Brenda Colella ² Anne L. Wheeler ^5,6 Jocelyn E. Harris ⁷ Robin E.A. Green ^2,8

• ¹ Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ² The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada
• ³ McMaster University, Hamilton, Ontario, Canada
• ⁴ Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
• ⁵ Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
• ⁶ Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
• ⁷ School of Rehabilitation Science, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
• ⁸ Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

In chronic moderate-to-severe TBI (msTBI), depression is one of the most common psychiatric consequences. Yet to date, there is limited understanding of its neural underpinnings. This study aimed to better understand this gap by examining seed-to-voxel connectivity in depression, with all voxel-wise associations seeded to the bilateral anterior prefrontal cortices (aPFC). In a secondary analysis of 32 patients with chronic msTBI and 17 age-matched controls acquired from the Toronto Rehab TBI Recovery Study database, the Personality Assessment Inventory Depression scale scores were used to group patients into an msTBI-Dep group (T ≥ 60; n = 13) and an msTBI-Non-Dep group (T < 60; n = 19). Resting-state fMRI scans were analyzed using seed-based connectivity analyses. Ftests, controlling for age and education, were used to assess differences in bilateral aPFC rsFC across the 3 groups. After nonparametric permutation testing, the left aPFC demonstrated significantly increased rsFC with the left (p = 0.041) and right (p = 0.013) fusiform gyri, the right superior temporal lobe (p = 0.032), and the right precentral gyrus (p = 0.042) in the msTBI-Dep group compared to controls. The msTBI-Non-Dep group had no significant rsFC differences with either group. To our knowledge, this study is the first to examine aPFC rsFC in a sample of patients with msTBI exclusively. Our preliminary findings suggest a role for the aPFC in the pathophysiology of depressive symptoms in patients with chronic msTBI. Increased aPFC-sensory/motor rsFC could be associated with vulnerability to depression post-TBI, a hypothesis that warrants further investigation.