Citation

Hogeveen J, Aragon DF, Rogge-Obando K, Campbell R, Shuttleworth CW, Rieger RE, Yeo R, Wilson JK, Fratzke V, Brandt E, Story Remer JH, Gill D, Mayer A, Cavanagh JF, Quinn D. J. Neurotrauma 2021; ePub(ePub): ePub.

Copyright

(Copyright © 2021, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2020.7363

PMID

unavailable

Abstract

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining which patients do or do not develop apathy post-TBI. Here we aimed to elucidate the impact of TBI on motivational neural circuits, and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected in patients with subacute mild TBI (N=44), chronic mild-to-moderate TBI (N=26), and non-brain-injured control participants (CTRL; N=28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating prior work suggesting that apathy has an enduring impact in TBI. vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Lastly, we subdivided the TBI group based on patients above versus below the threshold for "clinically-significant apathy," finding that TBI patients with clinically-significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically-significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represents an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Language: en

Keywords

MRI; NEUROPSYCHOLOGY; TRAUMATIC BRAIN INJURY; COGNITIVE FUNCTION