Background High‐level cognitive processes such as binding the processed data from sensory modules with elements stored in the memory involve the activity of long‐range pyramidal cells. These excitatory neuronal populations also provide input to a population of GABAAergic inhibitory interneurons, which in turn recruit feedback links to suppress the activity of the pyramidal cells. Interneuron networks generate rhythmic synchronization in the Gamma band driven by the time constant of the GABA receptors. Disrupted or desynchronized Gamma oscillations have been observed in patients of Alzheimer’s disease (AD). Earlier works have proposed the deficit in coherence between oscillations measured by EEG electrodes across the frontal lobe in the Gamma band in response to olfactory stimulation as a diagnostic marker of AD. This study examines the strength and spatial spread of Gamma band activity induced by auditory chirp stimulation as a marker for AD. The chirp signal is designed to entrain a target frequency of 40Hz at which the populations of inhibitory interneurons are known to operate. Method A session comprising 11 interleaved periods of 40sec ON and 20sec OFF auditory stimuli of 5kHz tone modulated by a 40Hz chirp at 0.1 duty cycle was administered to mild AD patients and non‐AD elderly participants with memory complaints, and EEG data were collected by a 10/20 system. Magnitude of 40Hz oscillations at different scalp positions during the ON cycles was measured as an indicator of the entrained Gamma oscillations. Result While 40Hz oscillations were recorded across a majority of electrodes in non‐AD demented participants with particular strengths in the temporal and frontal areas, the 40Hz entrainment occurred for a limited number of electrodes in AD patients. Conclusion Auditory chirp stimulation at 40Hz results in spatially distinguishable patterns of entrained Gamma oscillations in AD patients and non‐AD demented participants, and hence suggests a marker for AD. Despite this difference, the fact that 40Hz entrainment still occurs in regions of the brain in AD patients offers a positive indication for the possibility to employ such stimulation to reinvigorate the operation of the involved neural circuitry in therapy campaigns. Further studies are needed to assess such possibility.

Non-invasive gamma entrainment has shown promising results in alleviating cognitive symptoms of Alzheimer's disease in mice and humans. In this study, we examine improvements in the synchronization characteristics of the brain's oscillations induced by 40Hz auditory stimulation based on electroencephalography data recorded from a group of dementia patients. We observed that when the quality of entrainment surpasses a certain level, several indicators of brain synchronization significantly improve. Specifically, the entrained oscillatory activity maintains temporal phase stability in the frontal, parietal, and occipital regions, and persistent spatial phase coupling between them. In addition, notable theta-gamma phase-amplitude coupling is observed in these areas. Interestingly, a high theta power at rest predicts the quality of entrainment. We identify differentiating attributes of temporal/spatial synchronization and cross-frequency coupling in the data of two groups with entrained and non-entrained responses which point to enhanced network synchronization caused by entrainment and can explain its potential therapeutic effects.

Background The potential therapeutic effects of 40Hz gamma stimulation in Alzheimer's Disease (AD) has recently been under study (Suk et al. Alzheimer’s and Dementia 2020; Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020). While measuring the gamma power as a marker for brain entrainment is well established in the literature, some studies have focused on theta‐gamma coupling (TGC) (Etter, Guillaume, et al., Nature Communications 2019; Munia & Aviyente, Scientific Reports 2019) as TGC is known to play a critical role in working/spatial memory tasks. Synthetic 40Hz amplitude‐modulated auditory chirp sounds have been used to entrain gamma oscillations. As a natural alternative, we propose the canary song, which is innate, pleasant, and includes diverse modulating sounds with chirp frequencies up to 20Hz. Since harmonic components are present in entrained response of the brain (Jones et al., Journal of Alzheimer's Disease 2019) albeit at lower powers, entrainment with the 20Hz canary chirp song can be a substitute for the commonly used synthetic 40Hz sounds. Method We observed the entrainment characteristics for the complete course of a canary’s singing as well as for selective 20Hz chirp segments of the song on eight young adults with simultaneous EEG recording. We measured the power spectrum and TGC strength during the stimulus and rest intervals on selective independent components (IC) of the recorded response. Result Canary song’s 20Hz chirp increases the theta band and 20Hz oscillation activity. During the stimuli intervals, ICs were found in the response close to the midbrain area that were entrained by the 20Hz stimuli while also showing high power in the theta band. TGC with high values around 40 Hz was also observed during the 20 Hz chirp intervals. Conclusion Employing natural sounds for AD therapy campaigns offers a more pleasant and serene alternative to artificial sounds. We selected segments of canary’s natural song which can produce entrainment effects similar to those of the synthetic 40Hz auditory tones commonly used for brain entrainment. Other natural sounds such as those of cricket and woodpecker can also be good candidates for entraining the brain in AD therapy.

Gamma entrainment has been shown to enhance beta amyloid (Aβ) uptake in mouse models of Alzheimer's disease (AD) as well as improve cognitive symptoms of dementia in both humans and mice. Similar improvements have been reported for both invasive and non-invasive brain stimulation in the gamma oscillatory band, with 40 Hz auditory and visual sensory stimulants employed in non-invasive approaches. Non-invasive stimulation techniques possess the clear advantage of not requiring surgical procedures and can hence be applicable to a wider set of patients. The dataset introduced here was acquired with the aim of examining the network-level mechanisms governing the production of the brain's oscillatory activity during non-invasive auditory gamma-band stimulation, and thereby helping to explain the reported therapeutic effects of entrainment in AD patients. Thirteen elderly participants with memory complaints whose conditions were diagnosed as normal aging (non-AD) or mild AD based on the standard criteria for the diagnosis of AD including the mini-mental state exam (MMSE) took part in data collection in which EEG signals were recorded during auditory stimulation of the brain. The data collection session consisted of an initial one-minute rest followed by an alternating set of six stimulation trials interleaved with five rest trials. During each stimulation trial, an auditory stimulant in the form of a 40 Hz chirp was presented to the participant. The collected data from all participants were preprocessed following the full pipeline of Makoto with the use of EEGLAB and posted as a dataset named: Auditory Gamma Entrainment at OpenNeuro repository. The data record for each participant includes the EEG signal represented in standard BIDS format for one-minute rest followed by the auditory task data. A copy of the source EEG data is also provided in .txt format. The dataset can be used to study the characteristics of brain oscillations during entrainment, as well as for studies on auditory perception, analysis of resting state potentials in dementia patients, comparison of auditory evoked potentials with resting state potentials, ERP, ERSP, and SSAVP analysis of auditory response in dementia patients, time series analysis of the stimulation and rest trials, and brain connectivity analysis in dementia patients.

Background Non‐invasive 40Hz sensory‐induced brain entrainment has shown promising results in Alzheimer’s disease (AD) therapy (Chan et al., medRxiv, 2021; Chan et al., Alzheimer’s & Dementia, 2021). We previously reported on the network‐level mechanisms underlying the spatial and temporal coherence of the induced brain rhythms during gamma entrainment in dementia patients (Lahijanian et al., bioRxiv, 2021). Here, we posit that the induced gamma oscillations propagate as traveling waves circling each hemisphere of the cortex, and that the induction of such waves can explain the spatiotemporal coherence between the frontal and parietal/occipital regions reported to be involved in cognitive processes. Method EEG data were recorded from two healthy young adults during multi‐trial visual entrainment sessions with 22Hz flickering light. Due to the harmonic property of the brain’s entrained response (Jones et al., Journal of Alzheimer’s Disease, 2019), gamma entrainment was achieved at 44Hz. Separately, EEG data were recorded from 11 dementia patients in multi‐trial auditory entrainment sessions with 40Hz chirp input. The phase of the spatiotemporal pattern at the target gamma frequency was calculated across the entire scalp as an indicator of traveling waves. Result Shortly after the stimulation onset in the young healthy adults, a circling traveling wave is observed in each hemisphere (Fig. 1). The onset and the homogeneity of the induced wave pattern is modulated by the power of the 44Hz entrained oscillations (Fig. 2). The dementia patients can be divided into two groups of entrained and non‐entrained according to the induced gamma power (see Lahijanian et al., bioRxiv, 2021), and the travelling wave effect can be occasionally observed during the stimulation in the entrained group and not in the non‐entrained group. Conclusion Cortical traveling waves modulate the brain dynamics and play a critical role in functions ranging from sensory processing to memory consolidation (Muller et al., Nature Reviews Neuroscience, 2018). Gamma entrainment induces traveling waves that connect the occipital/parietal regions of the cortex to the frontal region through the temporal region. The traveling wave promotes spatiotemporal coherence across the brain and hence can serve as a network‐level mechanism for explaining the therapeutic effects of gamma entrainment.