Gamma Band Light Stimulation in Human Case Studies: Groundwork for Potential Alzheimer’s Disease Treatment

Abstract

Background: It is known that proteins associated with Alzheimer's disease (AD) pathogenesis are significantly reduced by 40 Hz entrainment in mice. If this were to translate to humans, verifying that such a light stimulus can induce a 40 Hz entrainment response in humans and harnessing insights from these case studies could be one step in the development of a multisensory device to prevent and treat AD. Objective: Verify the inducement of a 40 Hz response in the human brain by a 40 Hz light stimulus and obtain insights that could potentially aid in the development of a multisensory device for the prevention and treatment of AD. Methods: Electroencephalographic brain activity was recorded simultaneously with application of stimulus at different frequencies and intensities. Power spectral densities were analyzed. Results: Entrainment to visual stimuli occurred with the largest response at 40 Hz. The high intensity 40 Hz stimulus caused widespread entrainment. The number of electrodes demonstrating entrainment increased with increasing light intensity. Largest amplitudes for the high intensity 40 Hz stimulus were consistently found at the primary visual cortex. There was a harmonic effect at double the frequency for the 40 Hz stimulus. An eyes-open protocol caused more entrainment than an eyes-closed protocol. Conclusion: It was possible to induce widespread entrainment using a 40 Hz light stimulus in this sample cohort. Insights gleaned from these case studies could potentially aid in the development of a multisensory medical device to prevent and treat AD.

Gamma Entrainment Improves Synchronization Deficits in Dementia Patients

“…While stimulating the brain with 40Hz auditory or visual stimuli is referred to as entrainment, our results show that such stimulation does not necessarily cause notable entrained oscillatory activity in all brains. Based on earlier studies on entrainment 31,33,37 , a clear response of the brain to the stimulant frequency is expected as a peak in the spectrogram of the recorded response on that frequency. Accordingly, we propose a method to determine the occurrence of entrainment (see Methods).…”

“…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.…”

40-Hz Blue Light Changes Hippocampal Activation and Functional Connectivity Underlying Recognition Memory

“…A functional magnetic resonance imaging (fMRI) study measured the real-time response of the brain to flickering visual stimuli with a frequency varying from 1 to 40 Hz, and revealed that visual stimuli could selectively activate cortical areas and regulate specific brain connections ( Chai et al, 2019 ). In another ERP study, it was verified that 40, 60, and 80-Hz light stimulation induced the human brain response, and the greatest amplitude was always found in the primary visual cortex ( Jones et al, 2019 ). However, these studies did not show changes in the hippocampus or determine whether there were changes in brain activity related to memory tasks.…”

Deep Brain Stimulation for Alzheimer’s Disease: Tackling Circuit Dysfunction

“…A 40 Hz light flicker paradigm has also been explored in humans, demonstrating widespread 40 Hz entrainment (222), but a study in AD patients found no reduction of Aβ pathology as analyzed by PET (223). Further studies are required to evaluate the possible role of noninvasive direct cell modulation in human patients.…”