From Cortical Impact to Inattention: Real-Time Acetylcholine Disruption Links Brain Trauma to Attentional Deficits

Attentional deficits are prevalent and persistent after traumatic brain injury (TBI), yet our understanding of their etiology is incomplete. In uninjured rats, in vivo microdialysis studies show that task-evoked increases in acetylcholine (ACh) in the medial prefrontal cortex (mPFC) correlate with enhanced attentional performance. The goal of this study was to test the hypothesis that TBI decreases task-evoked ACh in the mPFC, compromises nucleus basalis of Meynert (nbM) cholinergic neuron morphology, and impairs attention. Adult male Sprague-Dawley rats trained on the three-choice serial reaction time (3-CSRT) task and then received either a controlled cortical impact or sham injury (n = 10/group). Dialysate samples were collected by in vivo microdialysis before and during the 3-CSRT task, and ACh levels were quantified using high-performance liquid chromatography. Cholinergic neurons in the contralateral/ipsilateral nbM were reconstructed and analyzed using the IMARIS software. The findings revealed a task-evoked decrease in ACh in the TBI group, a significant reduction in soma area/volume in the ipsilateral nbM, and impaired sustained attention as measured by performance on the 3-CSRT task. The findings support the hypothesis that TBI-induced attentional impairments are linked to disrupted real-time cholinergic signaling in the mPFC and associated structural changes in cholinergic neurons. These insights could inform the development of targeted interventions to improve quality of life for TBI survivors.