Scopolamine's Anticholinergic Effects on EEG Spectral, Aperiodic, Complexity, Microstates, and Heart Rate Variability

Scopolamine disrupts cholinergic mechanisms via nonspecific muscarinic antagonism. Centrally, excitatory neocortical innervations are antagonised causing spectral electroencephalography (EEG) changes and cognitive impairment. Peripherally, parasympathetic control of heart rate variability (HRV) is disrupted, although acute HRV effects of scopolamine are not well-defined.

Forty adults with depression received scopolamine hydrobromide (N = 24, 4-6 μg/kg) or glycopyrronium bromide (N = 16, 4-6 μg/kg) infusions. Twelve healthy adults received scopolamine (4-6 μg/kg) infusions. EEG and electrocardiography were recorded across 4 hours post-infusion. EEG spectral, aperiodic, Lempel Ziv complexity (LZC), and microstates analyses were performed. Electrocardiographic HRV metric: proportion of high frequency power (pHF) was calculated and modelled via pharmacokinetic-pharmacodynamic models to ascertain the HRV concentration-effect relationship.

Scopolamine increased delta power between 0.5 and 3.5 h (at 35 min: t = 3.6, p = 0.002). At 3 hours post-infusion, scopolamine increased aperiodic slope (t = -3.4, p = 0.047) and offset (t = -3.93, p = 0.003) parameters, reduced LZC (t = -4.5, p = 2 × 10^-4), and microstate D mean duration (t = -3.0, p = 0.039). EEG metrics correlated with drowsiness and alcohol-like stimulant ratings. Peripherally, scopolamine reduced HRV, with two-compartment pharmacokinetic models describing a delayed pHF effect via an effect compartment.

These effects corresponded to increased drowsiness, reduced excitation-inhibition ratio, and reduced HRV-implicating central and peripheral muscarinic mechanisms reminiscent of Alzheimer's-like cholinergic disruption.

anzctr.org.au identifier: ACTRN12619000569101 and ACTRN12622000228785.