From eyes‐closed to eyes‐open: Role of cholinergic projections in EC‐to‐EO alpha reactivity revealed by combining EEG and MRI

Abstract

Alpha rhythm (8 to 12 Hz) observed in EEG over human posterior cortex is prominent during eyes‐closed (EC) resting and attenuates during eyes‐open (EO) resting. Research shows that the degree of EC‐to‐EO alpha blocking or alpha desynchronization, termed alpha reactivity here, is a neural marker of cognitive health. We tested the role of acetylcholine in EC‐to‐EO alpha reactivity by applying a multimodal neuroimaging approach to a cohort of young adults and a cohort of older adults. In the young cohort, simultaneous EEG‐fMRI was recorded from twenty‐one young adults during both EO and EC resting. In the older cohort, functional MRI was recorded from forty older adults during EO and EC resting, along with FLAIR and diffusion MRI. For a subset of twenty older adults, EEG was recorded during EO and EC resting in a separate session. In both young and older adults, functional connectivity between the basal nucleus of Meynert (BNM), the major source of cortical acetylcholine, and the visual cortex increased from EC to EO, and this connectivity increase was positively associated with alpha reactivity; namely, the stronger the BNM‐visual cortex functional connectivity increase from EC to EO, the larger the EC‐to‐EO alpha desynchronization. In older adults, lesions of the fiber tracts linking BNM and visual cortex quantified by leukoaraiosis volume, associated with reduced alpha reactivity. These findings support a role of acetylcholine and particularly cholinergic pathways in mediating EC‐to‐EO alpha reactivity and suggest that impaired alpha reactivity could serve as a marker of the integrity of the cholinergic system.

EEG alpha reactivity and cholinergic system integrity in Lewy body dementia and Alzheimer’s disease

“…EEG data from three occipital electrodes (O1, O2, and Oz) were selected for the alpha reactivity analysis ( Fig. 2a) [17]. For each electrode separately, the power spectral density (PSD) was estimated using Bartlett's method with a frequency resolution of 0.25 Hz and a Hamming window.…”

“…The resulting PSD for the three electrodes was averaged across the 45 epochs and across the three electrodes for each condition separately (eyes open and eyes closed). Alpha reactivity was then calculated according to the following formula [17]: where alpha power was computed as the relative power within a frequency bin around the individual alpha peak frequency ± 2 Hz. Individual alpha peak frequencies were calculated by finding the peak in the PSD in the extended alpha frequency band from 4 to 14 Hz [20] using the eyes-closed data.…”

“…In the healthy brain, opening of the eyes leads to a marked attenuation of alpha power due to desynchronization of neuronal activity [15,16]. The magnitude of this reduction in alpha power from eyes closed to eyes opentermed alpha reactivity-has been suggested as a marker of cholinergic system integrity [17,18].…”

Decoding visual network‐related dynamic functional connectivity for eyes‐open and eyes‐closed using machine learning

“…10 In addition to resting state fMRI-based evidences, electroencephalography (EEG)-based and magnetoencephalography (MEG)-based methods also found different brain network topology between EO/EC, indicating that the characteristic brain active patterns might have physiological meanings. [11][12][13] The above findings suggested that the internetwork neural mechanisms might be distinctive between EO/EC. Therefore, resting state network measures could be potential neuroimaging-markers for discriminative analysis of EO/EC using machine learning.…”

Intrinsic activity temporal structure reactivity to behavioural state change is correlated with depressive symptoms

“…The GABA and glutamate systems, the primary inhibitory and excitatory transmitters in the brain, have been shown to be altered in MDD (Godfrey et al, 2018;Voineskos et al, 2019). As well as this, neuromodulators such as serotonin and dopamine, which influence neural excitability, are known to be affected in MDD (Belujon and Grace, 2017;Morrissette and Stahl, 2014) and to play a role in cortical activity changes between EC and EO conditions (Wan et al, 2019). It thus seems possible that the reported changes in cortical dynamic reactivity are related to changes in these systems (Hu et al, 2019;Ramirez-Mahaluf et al, 2017;Wiebking et al, 2014).…”