Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer's disease

Abstract

Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer’s disease, (AD), Parkinson’s disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. In this review, we discuss how neurologists manipulate brain oscillations with neuromodulation to treat diseases and how this can be leveraged to improve cognition and pathology underlying AD. While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40‐HZ gamma waves reduced AD‐specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.

An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment

“…Targeting gamma rhythms in AD is receiving growing interest as a therapeutic option due to available evidence for an involvement of high-frequency oscillations in AD pathology, and the promising entrainment effect emerged in both mouse models and patients ( Traikapi and Konstantinou, 2021 ; Chan et al, 2021b ). Sophisticated and multimodal tools for brain rhythm entrainment are now being developed ( Menardi et al, 2021 ).…”

“…It was suggested that 40 Hz gamma stimulation in mice models attenuate AD-related pathology (i.e., Aβ, p-tau, synapses, connectivity, and cognitive function loss) by inducing glial responses promoting neuroprotection. Gamma stimulation in humans seems to improve brain vessel dilatation, and thus, cerebral blood perfusion in AD patients ( Sprugnoli et al, 2021 ; Chan et al, 2021b ). On the other hand, the observed improvements in patients’ cognitive functions obtained by neuromodulation have been attributed to the enhancement and integration of information flow.…”

“…At the cellular level, gamma entrainment can potentially impact large-scale activity of fast-spiking PV + interneurons (i.e., from visual/auditory areas to deeper brain regions, such as the hippocampus; Catani et al, 2003 ; Kanwisher and Dilks, 2013 ). Indeed, it has been hypothesized that the beneficial effects of GENUS originate from the positive effect of gamma entrainment on excitation/inhibition imbalance, as it could prevent neurochemical alterations associated with Aβ (i.e., hyperexcitability) and induce neuroprotective mechanisms (e.g., microglia activation; Hijazi et al, 2020 ; Chan et al, 2021a , b , c ).…”

The magics of 40 hertz

“…Historically, drug-free approaches to treat brain diseases have included stimulation of the brain by electric pulses delivered inside the brain or from the outside, and magnetic pulses delivered from the outside of the brain. In this issue, Chan et al [2] discuss studies of such magnetic and electric interventions and their advantages and disadvantages, including electroconvulsive treatments and deep brain stimulation for different brain conditions, with comments on how these interventions may relate to brain oscillations.…”

Gamma Entrainment Improves Synchronization Deficits in Dementia Patients

“…Interventions based on stimulating neural populations in the gamma band have been recently proposed and are under examination on animal models of AD 22,[27][28][29] and in limited human studies [30][31][32][33][34][35][36] . These approaches aim to reinvigorate the functionality of the brain networks through synchronized pumping of rhythmic energy via one or multiple sensory modalities.…”