Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were \"sticky\", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

A frequency range exceeding approximately 30 Hz, denoted as the gamma frequency range, is associated with various cognitive functions, consciousness, sensory integration, short-term memory, working memory, encoding and maintenance of episodic memory, and retrieval processes. In this study, we proposed a new form of gamma stimulation, called gamma music, combining 40 Hz auditory stimuli and music. This gamma music consists of drums, bass, and keyboard sounds, each containing a 40 Hz frequency oscillation. Since 40 Hz stimuli are known to induce an auditory steady-state response (ASSR), we used the 40 Hz power and phase locking index (PLI) as indices of neural activity during sound stimulation. We also recorded subjective ratings of each sound through a questionnaire using a visual analog scale. The gamma music, gamma drums, gamma bass, and gamma keyboard sounds showed significantly higher values in 40 Hz power and PLI compared to the control music without a 40 Hz oscillation. Particularly, the gamma keyboard sound showed a potential to induce strong ASSR, showing high values in these indices. In the subjective ratings, the gamma music, especially the gamma keyboard sound, received more relaxed, comfortable, preferred, pleasant, and natural impressions compared to the control music with conventional gamma stimulation. These results indicate that our proposed gamma music has potential as a new method for inducing ASSR. Particularly, the gamma keyboard sound proved to be an effective acoustic source for inducing a strong ASSR while preserving the comfortable and pleasant sensation of listening to music. Our developed gamma music, characterized by its pleasantness to the human ear, offers a significant advantage for the long-term use of gamma stimulation. The utilization of this music could potentially reduce the physical and psychological burden on participants compared to conventional 40 Hz stimuli. This music is not only expected to contribute to fundamental neuroscience research utilizing ASSR but also to facilitate the implementation of gamma music-based interventions aimed at enhancing human cognitive functions in everyday life.

OBJECTIVE: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood. We hypothesized that invasive stimulation in the gamma frequency band increases microglial recruitment in the short term and reduces astrogliosis at the tissue-electrode interface.
METHODS: Male Long Evans rats were implanted with dual-shank silicon microelectrode arrays into the motor cortex. After implantation, rats received one hour of 40-Hz stimulation at a constant current of 10 μA using charge-balanced, biphasic pulses on one shank, and the other shank served as the nonstimulated control. Postmortem, tissue sections were stained with ectodermal dysplasia 1 (ED1) for activated microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and 4\',6-diamidino-2-phenylindole (DAPI) for nonspecific nuclei. Fluorescent intensity and cell number as a function of distance from the tissue-electrode interface were used to quantify all stained sections.
RESULTS: Fluorescent intensity for ED1 was nearly 40% lower for control than for stimulated sites (0-500 μm away from the implant), indicating increased microglial recruitment to the stimulated site (p < 0.05). Fluorescent intensity for GFAP was >67% higher for control than for stimulated sites (0-500 μm away from the implant), indicating reduced astrogliosis at the stimulated site (p < 0.05). No differences were observed in DAPI-stained sections between conditions.
CONCLUSIONS: These results suggest that short-term gamma stimulation modulates glial recruitment in the immediate vicinity of the microelectrode. Future studies will investigate the long-term effects of gamma stimulation on glial recruitment at the tissue-electrode interface as a strategy to improve long-term recording reliability.

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer\'s disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer\'s disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network.

Dementia prevalence is increasing globally, and symptom management and treatment strategies require further investigation. Music-based interventions have demonstrated some efficacy with respect to quality of life and symptom reduction, though limited with respect to cognition. This study reports on three case studies where the use of gamma stimulation over one year contributed to maintenance of cognition and increases in mood for participants with Alzheimer\'s disease or mild cognitive impairment. Auditory stimulation with isochronous sound at 40 Hz was delivered to participants via a commercially available vibroacoustic chair device five times per week for 30 min with assistance from caregivers. Further research is needed to assess the integration of this therapy in the overall care for persons with dementia.

Background Major depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, the findings suggested a significant clinical improvement in depression symptoms as measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with 37% of participants meeting the criteria for clinical response. The goal of the present research was to examine possible changes from baseline to posttreatment in resting-state electroencephalography (EEG) recordings using the same treatment protocol and to characterize basic changes in EEG related to treatment response. Materials and methods The study sample consisted of 19 individuals aged 18-70 years with a clinical diagnosis of MDD. The participants were assessed before and after a five-week treatment period, which consisted of listening to an instrumental musical track on a vibroacoustic device, delivering auditory and vibrotactile stimulus in the gamma-band range (30-70 Hz, with particular emphasis on 40 Hz). The primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to posttreatment and resting-state EEG. Results Analysis comparing MADRS score at baseline and post-intervention indicated a significant change in the severity of depression symptoms after five weeks (t = 3.9923, df = 18, p = 0.0009). The clinical response rate was 36.85%. Resting-state EEG power analysis revealed a significant increase in occipital alpha power (t = -2.149, df = 18, p = 0.04548), as well as an increase in the prefrontal gamma power of the responders (t = 2.8079, df = 13.431, p = 0.01442). Conclusions The results indicate that improvements in MADRS scores after rhythmic sensory stimulation (RSS) were accompanied by an increase in alpha power in the occipital region and an increase in gamma in the prefrontal region, thus suggesting treatment effects on cortical activity in depression. The results of this pilot study will help inform subsequent controlled studies evaluating whether treatment response to vibroacoustic stimulation constitutes a real and replicable reduction of depressive symptoms and to characterize the underlying mechanisms.

BACKGROUND: We and collaborators discovered that flickering lights and sound at gamma frequency (40 Hz) reduce Alzheimer\'s disease (AD) pathology and alter immune cells and signaling in mice. To determine the feasibility of this intervention in humans we tested the safety, tolerability, and daily adherence to extended audiovisual gamma flicker stimulation.
METHODS: Ten patients with mild cognitive impairment due to underlying AD received 1-hour daily gamma flicker using audiovisual stimulation for 4 or 8 weeks at home with a delayed start design.
RESULTS: Gamma flicker was safe, tolerable, and adherable. Participants\' neural activity entrained to stimulation. Magnetic resonance imaging and cerebral spinal fluid proteomics show preliminary evidence that prolonged flicker affects neural networks and immune factors in the nervous system.
CONCLUSIONS: These findings show that prolonged gamma sensory flicker is safe, tolerable, and feasible with preliminary indications of immune and network effects, supporting further study of gamma stimulation in AD.

In recent years, music-based interventions (MBIs) have risen in popularity as a non-invasive, sustainable form of care for treating dementia-related disorders, such as Mild Cognitive Impairment (MCI) and Alzheimer\'s disease (AD). Despite their clinical potential, evidence regarding the efficacy of MBIs on patient outcomes is mixed. Recently, a line of related research has begun to investigate the clinical impact of non-invasive Gamma-frequency (e.g., 40 Hz) sensory stimulation on dementia. Current work, using non-human-animal models of AD, suggests that non-invasive Gamma-frequency stimulation can remediate multiple pathophysiologies of dementia at the molecular, cellular and neural-systems scales, and, importantly, improve cognitive functioning. These findings suggest that the efficacy of MBIs could, in theory, be enhanced by incorporating Gamma-frequency stimulation into current MBI protocols. In the current review, we propose a novel clinical framework for non-invasively treating dementia-related disorders that combines previous MBIs with current approaches employing Gamma-frequency sensory stimulation. We theorize that combining MBIs with Gamma-frequency stimulation could increase the therapeutic power of MBIs by simultaneously targeting multiple biomarkers of dementia, restoring neural activity that underlies learning and memory (e.g., Gamma-frequency neural activity, Theta-Gamma coupling), and actively engaging auditory and reward networks in the brain to promote behavioural change.