The vast number of nerve cells in the human brain — about 86 billion of them according to one estimate — appear to coordinate their activities by firing in synchrony.
One particular firing frequency, at about 40 pulses per second (40 Hz) in the gamma frequency range, plays a pivotal role in brain functions, such as conscious awareness, perception, and memory.
Neuroscientists have discovered, for example, that on the rare occasions when people become aware that they are dreaming, known as lucid dreaming, the strength of electrical oscillations at 40 Hz intensifies in their brains.
There is also some evidence that stimulating a sleeping volunteer’s brain with a weak electric field pulsing at low gamma frequencies can induce lucid dreams.
Other research has found that the brains of people who practice some forms of meditation, which involves highly focused attention, have an unusually strong gamma signal during meditation and “instructed mind-wandering” practices.
Conversely, scientists have found disruptions in the gamma range in several neurological disorders, including Alzheimer’s disease.
“There is evidence that gamma activity is altered in people with dementia,” said Annabelle Singer, Ph.D., a neuroscientist at the Georgia Institute of Technology and Emory University in Atlanta.
“Exactly how gamma changes depends on what brain regions are measured and what the participant is doing — like during a task vs. awake but resting,” she added.
Alzheimer’s disease is an incurable, degenerative form of dementia that damages parts of the brain that play a role in thought, memory, and language.
The early stages, known as mild cognitive impairment (MCI), involve relatively mild loss of memory. However, the later stages include debilitating symptoms, such as getting lost in once familiar places, poor judgment, and changes in mood and personality.
The Centers for Disease Control and Prevention (CDC) estimate that in 2020, 5.8 million people in the United States were living with Alzheimer’s.
Sensory flicker as a treatment?
Dr. Singer and her colleagues in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University are developing a novel approach to treating the disease that involves light and sound pulsing at 40 Hz.
The idea is that the flickering sensory stimuli will “entrain” nerves deep within the brain to fire at the same frequency, which may, over time, restore their lost connectivity.
In murine models of Alzheimer’s, the researchers found that sensory entrainment at gamma frequencies leads to immune changes that clear beta-amyloid, a toxic protein associated with the disease.
However, the effects of this type of sensory flicker on the brains of people with Alzheimer’s are unknown.
The question also remained whether humans would tolerate the treatment and stick with the necessary daily regimen of sensory stimulation.
To test its safety and tolerability, Dr. Singer’s lab enrolled 10 participants with MCI associated with early Alzheimer’s.
They selected people with mild disease to ensure that they would be able to describe how well they tolerated the treatment.
In addition, they excluded anyone with a history of migraine, tinnitus, or seizures from the study because flickering sensory stimuli can exacerbate these conditions.
The researchers randomly assigned the volunteers to either 8 weeks of 1 hour of flicker treatment per day or 4 weeks without treatment followed by 4 weeks of treatment.
This study design allowed them to account for any effects related to the progression of the disease and the measurements that they carried out as part of the experiment.
During the treatment, the participants wore an experimental visor and headphones that delivered flashes of light and sound at 40 Hz.
The researchers report that no severe adverse events occurred in relation to these flickering stimuli.
Among the mild adverse events that the treatment may or may not have caused were dizziness, tinnitus, headache, and worsened hearing loss.
Electroencephalography (EEG) recordings revealed that the participants’ brain activity synchronized with the 40-Hz stimulation.
In addition, MRI brain scans after 8 weeks of daily flicker suggested a strengthening of connectivity between two nodes of the brain’s default mode network, which is involved in self-referential thought processes.
Connectivity between these particular nodes is known to weaken as Alzheimer’s disease progresses.
After 8 weeks of treatment, there was also evidence from immune signaling molecules in the participants’ cerebrospinal fluid that the 40-Hz brain stimulation was modifying their immune system.
The results appear in the journal Translational Research & Clinical Interventions.
Deep brain structures
ishonest asked Dr. Singer why the team chose flickering sound and light to entrain people’s brain waves rather than transcranial electrical or magnetic stimulation.
“We think other forms of 40-Hz stimulation could work because we know that has been the case in animal studies,” she said. “But a key challenge is reaching deep brain structures involved in Alzheimer’s disease, especially in humans with large brains.”
She said that it remained unclear whether existing forms of magnetic or electrical stimulation would be able to drive 40-Hz neural activity in these deep brain structures.
Further trials of flicker treatment over longer periods will show how the effects that occurred in this preliminary study change over time.
“In animal studies, some of the beneficial effects of gamma sensory stimulation wear off a week or more after stimulation stops,” said Dr. Singer. “That’s one of the reasons we have participants perform stimulation every day.”
“That said, we won’t know how long the effects last in humans without further study,” she added.
“But we now have some very good arguments for a larger, longer study with more people,” he concludes.
Limitations of the research
The trial also lacked a “sham stimulation” control condition for comparison because the team’s research in mice showed that random sensory flicker actually increased levels of beta-amyloid in the animals’ brains.
“It is unclear what stimulus patterns might be used as an appropriate placebo control for audiovisual flicker,” they write.
It is also worth noting that Dr. Singer owns shares in Cognito Therapeutics — a company that partially funded the study and aims to develop gamma stimulation- related products.
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