A review article published this week in the Journal of Internal Medicine points to early evidence that gamma rhythm stimulation could be a treatment for neurological disorders including Alzheimer’s disease (AD). The review of studies was conducted by the same lab at MIT that published a groundbreaking study in 2016 that first built interest in the notion that light flickering at a particular gamma-band brain rhythm could produce therapeutic benefit to patients with AD.
Brain rhythms, often called brain waves, produced by the activity within the network of brain cells and circuits enable brain functions such as perception and cognition. MIT researchers have shown the lower-range gamma rhythms around 40 cycles a second—or 40 Hz—are vital to memory processes and are also associated with specific cellular and molecular changes in the brain.
“What started in 2016 with optogenetic and visual stimulation in mice has expanded to a multitude of stimulation paradigms, a wide range of human clinical studies with promising results and is narrowing in on the mechanisms underlying this phenomenon,” wrote the review authors including Li-Huei Tsai, Picower professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT.
Despite the promise and a broadening range of studies looking into the phenomenon, the authors cautioned that much of the clinical data is still preliminary and that animal studies examining it have not produced definitive evidence.
“Research into the clinical potential of these interventions is still in its nascent stages,” the researchers, led by MIT postdoc Cristina Blanco-Duque, wrote in introducing the review. “The precise mechanisms underpinning the beneficial effects of gamma stimulation in Alzheimer’s disease are not yet fully elucidated, but preclinical studies have provided relevant insights.”
In total, the MIT investigators summarized the result of 16 different clinical studies that have used gamma frequency sensory stimulation, or exposure to light, sound, tactile, or a combination; trans cranial alternating current stimulation (tACS), in which a brain region is stimulated via scalp electrodes; or transcranial magnetic stimulation (TMS), in which electric currents are induced in a brain region using magnetic fields.
These studies showed that sensory stimulation appears to affect multiple regions in the brain, while tACS and TMS are more regionally focused (though those brain regions still connect and interact with others). In total, the authors noted, the studies show both uneven and encouraging evidence on the potential of the potential for this method to have clinical benefit. In fact, in multiple AD studies the sensory stimulation was shown to be both safe and well tolerated by patients.
But while these studies have shown potential benefits for AD patients including improved memory, cognition, and sleep, as well as physiological reduction in brain atrophy, the application of sensory stimulation has not shown a reduction the amyloid or tau proteins that cause disease progression. Studies examining the effects of tACS were the most common and showed similar results depending on the brain region stimulated, and have even showed some lasting benefits after the treatments ended. Some of the studies even showed effects on measures of amyloid and tau proteins, blood flow, neuromodulatory chemical activity, or immune activity.
“The most important test for gamma stimulation is without a doubt whether it is safe and beneficial for patients,” the authors wrote. “So far, results from several small trials on sensory gamma stimulation suggest that it is safe, evokes rhythmic EEG brain responses, and there are promising signs for AD symptoms and pathology. Similarly, studies on transcranial stimulation report the potential to benefit memory and global cognitive function even beyond the end of treatment.”
While promising evidence exists the authors wrote that more definitive clinical studies are needed and added that there are currently 15 separate studies of gamma stimulation in process, including a Phase III clinical trial by Cognito Therapeutics—a licensee of MIT’s technology—that will ultimately enroll hundreds of patients. Other studies are underway examining the effects gamma stimulation may have on other neurological conditions, as well as whether it can benefit cancer patients experiencing cognitive effects chemotherapy—also referred to a “chemobrain.”
“Larger clinical studies are required to ascertain the long-term benefits of gamma stimulation,” the authors wrote. “In animal models the focus should be on delineating the mechanism of gamma stimulation and providing further proof of principle studies on what other applications gamma stimulation may have.”
