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

Abstract

Research on light modulation has typically examined the wavelength, intensity, and exposure time of light, and measured rhythm, sleep, and cognitive ability to evaluate the regulatory effects of light variables on physiological and cognitive functions. Although the frequency of light is one of the main dimensions of light, few studies have attempted to manipulate it to test the effect on brain activation and performance. Recently, 40-Hz light stimulation has been proven to significantly alleviate deficits in gamma oscillation of the hippocampus caused by Alzheimer’s disease. Although this oscillation is one of the key functional characteristics of performing memory tasks in healthy people, there is no evidence that 40-Hz blue light exposure can effectively regulate brain activities related to complex cognitive tasks. In the current study, we examined the difference in the effects of 40-Hz light or 0-Hz light exposure on brain activation and functional connectivity during a recognition memory task. Through joint augmentation of visual area activation, 40-Hz light enhanced brain areas mostly in the limbic system that are related to memory, such as the hippocampus and thalamus. Conversely, 0-Hz light enhanced brain areas mostly in the prefrontal cortex. Additionally, functional connection analysis, with the hippocampus as the seed point, showed that 40-Hz light enhanced connection with the superior parietal lobe and reduced the connection with the default network. These results indicate that light at a frequency of 40 Hz can change the activity and functional connection of memory-related core brain areas. They also indicate that in the use of light to regulate cognitive functions, its frequency characteristics merit attention.

Audiovisual gamma stimulation for the treatment of neurodegeneration

“…Different light wavelengths (i.e., colors) were tested, with some groups reporting enhanced gamma brain activity with red light [18], or enhanced connectivity with violet light as compared to white light [20]. Blue light was also used to induce 40 Hz brain activity and was shown to increase hippocampal and visual cortex activation using functional magnetic resonance imaging (fMRI) measures, though this study did not have a white light stimulation arm [21]. Of interest, invisible spectral flicker at 40 Hz was also shown to induce 40 Hz brain activity and was comparable in engaging cortical brain activation to flickering white light at the same frequency [22].…”

“…Multiple studies have shown that gamma sensory stimulation can increase cerebral cortical activity in different brain areas as measured by fMRI, positron emission tomography (PET), and EEG recordings. In a study of 42 cognitively normal adults, a single session of 40 Hz blue light increased hippocampal and visual cortex activation as measured by task‐based fMRI [21]. However, after this single stimulation, there were no changes in response accuracy or response time despite increased brain activation.…”

Gamma oscillations and application of 40‐Hz audiovisual stimulation to improve brain function

“…Additionally, an EEG study showed that an increase was found in the connectivity between dorsolateral prefrontal and visual cortices under rhythmic visual stimulation (6‐, 10‐, 15‐, and 40‐Hz) compared with no increase could be found in no flicker condition (You et al, 2020 ). Forty‐hertz blue light stimulation has been shown to activate the visual cortex and hippocampus, improving the functional connectivity between the hippocampus and superior parietal lobe while decreasing the functional connectivity between the hippocampus and the default mode network (DMN), according to a functional magnetic resonance imaging (fMRI) study (Lin et al, 2021 ). Meanwhile, 40‐Hz light flicker could alter microstate metrics representing activation or deactivation states of brain networks with different functions and adjust functional state of brain networks to make them work (Zhang et al, 2021 ).…”

“…Herrmann ( 2001 ) observed that when flicker light stimulation frequency was set from 1 to 100 Hz in 1‐Hz steps, event‐related potentials presented steady‐state potentials with significant resonance phenomena around 10, 20, 40, and 80 Hz in 10 healthy volunteers. In the current state of clinical practice, studies have been mostly conducted with 40‐Hz light stimulation on cognitive function (Lin et al, 2021 ; You et al, 2020 ; Zhang et al, 2021 ). Specifically, light flickering at 34–38 Hz with high‐intensity red or white light has been shown to entrain stronger and wider gamma oscillations than lower intensity light stimulation (Jones et al, 2019 ; Lee et al, 2021 ; Noda et al, 2021 ).…”

Transcranial alternating current stimulation combined with sound stimulation improves cognitive function in patients with Alzheimer’s disease: Study protocol for a randomized controlled trial

“…It was found that tACS at specific frequencies may lead to entrainment concussion at the target stimulation frequency ( Kasten and Herrmann, 2017 ). Enhancing brain gamma-band wave activity can more directly enhance cognitive function or modulate the neuropathology of cognitive dysfunction ( Kim et al, 2021 ; Lin et al, 2021 ; Yu et al, 2022 ).…”