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We assessed the structure–function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain ( p  < 0.001) or thalamus volumes ( p  < 0.001) than healthy volunteers. Healthy SAI responders (> 10% SAI) had more basal forebrain volume than non-responders ( p  = 0.004) or patients with MCI ( p  < 0.001). More basal forebrain volume was associated with stronger SAI in healthy volunteers ( r  = 0.33,  p  < 0.05) but not patients with MCI. There was no significant relationship between thalamus volumes and SAI. Basal forebrain volume is associated with cholinergic function (SAI) in healthy volunteers but not in MCI patients. The in-vivo investigation of the structure–function relationship could further our understanding of the human cholinergic system in patients with suspected or known cholinergic system degeneration.

The relationship between cholinergic system brain structure and function in healthy adults and patients with mild cognitive impairment