Increased Cholinergic Activity in Mild Traumatic Brain Injury: Preliminary Evidence from [¹⁸F]FEOBV PET Study

Mild traumatic brain injury (mTBI) is a prevalent condition. While symptoms typically resolve within a few weeks, a subset of individuals experience persistent cognitive symptoms. It is not known why symptoms persist in some individuals. Cholinergic projections from the basal forebrain (BF) support attention and memory and may be affected in mTBI. Therefore, we investigated putative BF cholinergic alterations in chronic mTBI using [¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]FEOBV) positron emission tomography (PET) and examined associations with cognitive performance. Ten individuals with chronic mTBI (≥1-year post-injury) and 23 healthy controls underwent [¹⁸F]FEOBV PET imaging to assess vesicular acetylcholine transporter (VAChT) levels in the BF and completed cognitive testing. We found significantly increased [¹⁸F]FEOBV uptake in the BF of mTBI participants (M = 4.84, SD = 0.48) relative to controls (M = 4.54, SD = 0.36, p = 0.043). In mTBI, greater [¹⁸F]FEOBV uptake correlated with faster processing speed (p = 0.014). mTBI participants performed worse than controls on all cognitive tests, with the largest group differences in working memory (d = -0.84), executive function (d = -0.65), and processing speed (d = -0.53). This study is the first to evaluate cholinergic changes following mTBI in human participants. mTBI was associated with increased cholinergic functions in the BF. As greater VAChT levels were linked to better cognitive performance in the mTBI sample, this finding may reflect cholinergic compensation in chronic mTBI.