White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Construction and validation of a brain magnetic resonance imaging template for normal older Koreans.

BACKGROUND: Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size have low brain variability, improving the accuracy of spatial normalization. Using population-specific template improves accuracy of spatial normalization because brain morphology varies according to ethnicity and age. METHODS: We constructed a brain template of normal Korean elderly (KNE200) using MRI scans 100 male and 100 female aged over 60 years old with normal cognition. We compared the deformation after spatial normalization of the KNE200 template to that of the KNE96, constructed from 96 cognitively normal elderly Koreans and to that of the brain template (OCF), constructed from 434 non-demented older Caucasians to examine the effect of sample size and ethnicity on the accuracy of brain template, respectively. We spatially normalized the MRI scans of elderly Koreans and quantified the amount of deformations associated with spatial normalization using the magnitude of displacement and volumetric changes of voxels. RESULTS: The KNE200 yielded significantly less displacement and volumetric change in the parahippocampal gyrus, medial and posterior orbital gyrus, fusiform gyrus, gyrus rectus, cerebellum and vermis than the KNE96. The KNE200 also yielded much less displacement in the cerebellum, vermis, hippocampus, parahippocampal gyrus and thalamus and much less volumetric change in the cerebellum, vermis, hippocampus and parahippocampal gyrus than the OCF. CONCLUSION: KNE200 had the better accuracy than the KNE96 due to the larger sample size and was far accurate than the template constructed from elderly Caucasians in elderly Koreans.

Optimal flickering light stimulation for entraining gamma rhythms in older adults.

With aging, optimal parameters of flickering light stimulation (FLS) for gamma entrainment may change in the eyes and brain. We investigated the optimal FLS parameters for gamma entrainment in 35 cognitively normal old adults by comparing event-related synchronization (ERS) and spectral Granger causality (sGC) of entrained gamma rhythms between different luminance intensities, colors, and flickering frequencies of FLSs. ERS entrained by 700 cd/m2 FLS and 32 Hz or 34 Hz FLSs was stronger than that entrained by 400 cd/m2 at Pz (p < 0.01) and 38 Hz or 40 Hz FLSs, respectively, at both Pz (p < 0.05) and Fz (p < 0.01). Parieto-occipital-to-frontotemporal connectivities of gamma rhythm entrained by 700 cd/m2 FLS and 32 Hz or 34 Hz FLSs were also stronger than those entrained by 400 cd/m2 at Pz (p < 0.01) and 38 Hz or 40 Hz FLSs, respectively (p < 0.001). ERS and parieto-occipital-to-frontotemporal connectivities of entrained gamma rhythms did not show significant difference between white and red lights. Adverse effects were comparable between different parameters. In older adults, 700 cd/m2 FLS at 32 Hz or 34 Hz can entrain a strong gamma rhythm in the whole brain with tolerable adverse effects.

Optimal flickering light stimulation for entraining gamma waves in the human brain.

Although light flickering at 40 Hz reduced Alzheimer's disease (AD) pathologies in mice by entraining gamma waves, it failed to reduce cerebral amyloid burden in a study on six patients with AD or mild cognitive impairment. We investigated the optimal color, intensity, and frequency of the flickering light stimulus for entraining gamma waves in young adults. We compared the event-related synchronization (ERS) values of entrained gamma waves between four different light colors (white, red, green, and blue) in the first experiment and four different luminance intensities in the second experiment. In both experiments, we compared the ERS values of entrained gamma waves between 10 different flickering frequencies from 32 to 50 Hz. We also examined the severity of six adverse effects in both experiments. We compared the propagation of gamma waves in the visual cortex to other brain regions between different luminance intensities and flickering frequencies. We found that red light entrained gamma waves most effectively, followed by white light. Lights of higher luminance intensities (700 and 400 cd/m2) entrained stronger gamma waves than those of lower luminance intensities (100 and 10 cd/m2). Lights flickering at 34-38 Hz entrained stronger and more widely spread beyond the visual cortex than those flickering at 40-50 Hz. Light of 700 cd/m2 resulted in more moderate-to-severe adverse effects than those of other luminance intensities. In humans, 400 cd/m2 white light flickering at 34-38 Hz was most optimal for gamma entrainment.