Optimal gamma-band entrainment of visual cortex

Abstract

Visual entrainment is a powerful and widely used research tool to study visual information processing in the brain. While many entrainment studies have focused on frequencies around 14-16 Hz, there is renewed interest in understanding visual entrainment at higher frequencies (e.g., gamma-band entrainment). Notably, recent groundbreaking studies have demonstrated that gamma-band visual entrainment at 40 Hz may have therapeutic effects in the context of Alzheimer's disease (AD) by stimulating specific neural ensembles, which utilize GABAergic signaling. Despite such promising findings, few studies have investigated the optimal parameters for gamma-band visual entrainment. Herein, we examined whether visual stimulation at 32, 40, or 48 Hz produces optimal visual entrainment responses using high-density magnetoencephalography (MEG). Our results indicated strong entrainment responses localizing to the primary visual cortex in each condition. Entrainment responses were stronger for 32 and 40 Hz relative to 48 Hz, indicating more robust synchronization of neural ensembles at these lower gamma-band frequencies. In addition, 32 and 40 Hz entrainment responses showed typical patterns of habituation across trials, but this effect was absent for 48 Hz. Finally, connectivity between visual cortex and parietal and prefrontal cortices tended to be strongest for 40 relative to 32 and 48 Hz entrainment. These results suggest that neural ensembles in the visual cortex may resonate at around 32 and 40 Hz and thus entrain more readily to photic stimulation at these frequencies. Emerging AD therapies, which have focused on 40 Hz entrainment to date, may be more effective at lower relative to higher gamma frequencies, although additional work in clinical populations is needed to confirm these findings. PRACTITIONER POINTS: Gamma-band visual entrainment has emerged as a therapeutic approach for eliminating amyloid in Alzheimer's disease, but its optimal parameters are unknown. We found stronger entrainment at 32 and 40 Hz compared to 48 Hz, suggesting neural ensembles prefer to resonate around these relatively lower gamma-band frequencies. These findings may inform the development and refinement of innovative AD therapies and the study of GABAergic visual cortical functions.

Keywords: MEG; gamma activity; magnetoencephalography; visual entrainment.

FIGURE 1

Schematic of entrainment task design. (a) A white dot was presented on a gray background and flickered on‐and‐off at either 32 Hz, 40 Hz, or 48 Hz. Each trial was preceded by a fixation dot that was either black (80% of trials) or blue (20% of trials); participants were instructed to respond to the blue dot with a button press made with the index finger. The blue dot trials were excluded from further analysis. (b) Sine waves illustrating entrainment patterns for each of the three frequencies.

FIGURE 2

Sensor and source level activity during visual entrainment. (a) Averaged time‐frequency spectrograms from a posterior sensor (MEG2343) for 48 Hz (top), 40 Hz (middle), and 32 Hz (bottom) entrainment conditions. Time (ms) is shown on the x‐axis and frequency (Hz) on the y‐axis, and the color scale illustrates the percent change in oscillatory power relative to the baseline period (−600 to 0 ms). Clear entrainment can be seen at each fundamental driving frequency, and at the 2nd harmonic for the 40 and 32 Hz conditions. (b) Mean beamformer images (pseudo‐t; see color bar) of the entrainment frequency for (from top to bottom) the 48, 40, and 32 Hz conditions, as well as the grand average of all three entrainment conditions. The functional images show that entrainment peaked in a consistent primary occipital cortical region for each stimulation frequency.

FIGURE 3

Oscillatory power at each entrainment frequency. The brain map (top right) depicts the average entrainment response across all three entrainment conditions and all participants (i.e., the grand average). The box plots illustrate the entrainment response from 500 to 1000 ms for each frequency condition separately, which was extracted from bilateral occipital peaks depicted in the brain map and averaged across hemispheres. The X denotes the mean, the box edges are the first and third quartiles, and the whiskers indicate the minima and maxima. The surrounding violin plots illustrate the probability density. A repeated measures ANOVA revealed that the entrainment response was strongest for 32 and 40 Hz relative to 48 Hz (F _2,48 = 5.98, p = .005).

FIGURE 4

Habituation of entrainment responses. The entrainment response amplitude (% change relative to baseline) per stimulation frequency is displayed on the y‐axis, and trial number is on the x‐axis. The lines represent the slope of the entrainment response decrease over trials (i.e., habituation) per condition, with the shading surrounding each line indicating the standard error of the mean. Linear mixed effects (LME) analyses revealed that the 32 (p < .001) and 40 Hz (p = .02) entrainment responses habituated, such that the responses became weaker as a function of trial number. However, this effect was not present at the 48 Hz stimulation frequency (p = .29).

FIGURE 5

Differences in functional connectivity between the visual cortex and the whole brain at each entrainment frequency. The brain map (middle) depicts the voxel‐wise ANOVA, which compared the connectivity between each voxel and the primary visual cortex at the entrainment frequency for each entrainment condition. The box plots illustrate the strength of connectivity for the left precentral gyrus (left) and the left inferior parietal lobule (right) for each entrainment condition. The X denotes the mean, the box edges are the first and third quartiles, and the whiskers indicate the minima and maxima. The surrounding violin plots illustrate the probability density. *p < .01; **p < .001.