Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice

Gamma‐patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease

“…Of note, the 40 Hz sensory stimulation neither affected LTP induced by our standard (200 Hz) HFS nor enhance a relatively small LTP induced by a weak HFS (100 Hz) conditioning protocol in wild-type animals (Untreated vs. 40 Hz, p = .2204 and p = .8828, respectively; Figure 3c,e,f). Moreover, while brief 40 Hz light stimulation has been reported to disturb performance of a behavioural exploration task by wild-type mice (Soula et al, 2023), we did not observe a significant effect of combined audio and visual stimulation on spontaneous movement of wild-type rats under our experimental conditions ( p = .8205, Untreated versus 40 Hz, 12 rats in each group, Figure 3d).…”

“…The attempts to restore/influence gamma power in AD are still at an investigational stage, as no changes in AD biomarkers in humans after such treatment have been reported to date (Manippa et al, 2022). However, gamma‐patterned AD treatment has a clear clinical potential because a steady state gamma induced in sensory cortex can propagate into deeper brain areas in rodents (Adaikkan et al, 2019; Li et al, 2021; Martorell et al, 2019; Soula et al, 2023) and humans (Jones et al, 2019). Given the importance of corticosteroids in mediating circadian rhythms (Oster et al, 2017), our data on beneficial effects of 40 Hz sensory stimulation in corticosterone‐injected APP transgenic rats (Figure 2), which are in accord with findings that similar sensory stimulation improves the circadian clock in APP/PS1 mice (Yao et al, 2020) and sleep in AD patients (Cimenser et al, 2021), support this approach.…”

The oscillating mystery: The effects of forty‐hertz entrainment in treating Alzheimer's disease

“…This improvement is attributed to the reduction of accumulated amyloid‐β (Aβ) proteins and the enhancement of microglial function, both of which are associated with the disease. However, these findings have been challenged by recent research [2] conducted by Prof. Buzsáki and published in Nature Neuroscience . In this study, the research team utilized two AD mouse models, specifically APP/PS1 and 5xFAD, to explore the effects of both acute and chronic 40‐Hz light stimulation on Aβ, microglia, and gamma oscillations.…”

Gamma sensory entrainment for cognitive improvement in neurodegenerative diseases: opportunities and challenges ahead

“…Despite some of the successful studies reviewed above, it is important to note that some groups have also reported failure to replicate the original results. For example, in a very recent study, Soula et al (2023) used APP/PS1 and 5xFAD animal models and showed that application of both acute (10 min baseline followed by 1 h stimulation before animals were sacrificed) and chronic (1 h stimulation for consecutive 7 days before animals were sacrificed) 40 Hz visual flickering did not entrain deeper structures. The results further showed no obvious changes in Aβ load or microglia morphology in the animals ( Soula et al, 2023 ).…”

“…For example, in a very recent study, Soula et al (2023) used APP/PS1 and 5xFAD animal models and showed that application of both acute (10 min baseline followed by 1 h stimulation before animals were sacrificed) and chronic (1 h stimulation for consecutive 7 days before animals were sacrificed) 40 Hz visual flickering did not entrain deeper structures. The results further showed no obvious changes in Aβ load or microglia morphology in the animals ( Soula et al, 2023 ). Another study reported that optogenetic stimulation of PV + neurons in 5xFAD mice increased Aβ plaques in the basal forebrain rather than decrease the load ( Wilson et al, 2020 ).…”