A new study published in Brain Communications has uncovered abnormal brain wave activity in individuals with Alzheimer’s disease, suggesting a potential new biomarker for tracking the condition and its related symptoms. Researchers detected a specific type of fast brain rhythm known as high-frequency oscillations in Alzheimer’s patients—even in those who did not show obvious signs of epilepsy. These oscillations were more pronounced in patients with subclinical epileptic activity, and their levels responded differently to an anti-seizure medication depending on the presence or absence of epilepsy.
Alzheimer’s disease is primarily known for its impact on memory and cognition, but many people with the condition also experience seizures or abnormal electrical activity in the brain. These disturbances may go unnoticed without specialized testing, yet they are believed to worsen memory loss and accelerate cognitive decline. Researchers have long sought reliable indicators of this hidden hyperactivity, especially ones that could guide treatment decisions.
One promising candidate is the presence of high-frequency oscillations, or HFOs—brief, rapid bursts of electrical activity in the brain that have previously been linked to epilepsy. Although high-frequency oscillations have been studied in people with drug-resistant epilepsy, they had not been observed in people with Alzheimer’s disease until now. In this study, the researchers wanted to find out whether high-frequency oscillations could be detected in Alzheimer’s patients using non-invasive brain scans and whether these signals varied depending on the presence of epileptic activity.
“My epilepsy colleagues at UCLA discovered high-frequency oscillations as a sign of epilepsy in animal models of epilepsy and in brain recordings from human epilepsy patients. Based on my research into epilepsy and associated cognitive decline in Alzheimer’s disease, we wanted to know if high-frequency oscillations are present,” said study author Keith Vossel, a professor of neurology and director of Alzheimer’s research programs at UCLA.
The researchers used magnetoencephalography (MEG), a technique that records magnetic signals generated by brain activity. They analyzed 10-minute MEG recordings from three groups of participants: eight people with Alzheimer’s disease and subclinical epileptic activity, six with Alzheimer’s disease but no detectable epileptic activity, and eight healthy individuals.
All participants with Alzheimer’s disease were part of a larger clinical trial testing the effects of the anti-seizure drug levetiracetam on cognitive function. MEG data were collected before and after a four-week course of the drug, separated by a washout period, allowing each person to serve as their own control.
The research team focused on two types of high-frequency oscillations: ripples (between 80 and 250 Hz) and fast ripples (between 250 and 500 Hz). These fast rhythms were measured across multiple brain regions in both the left and right hemispheres. To identify and classify high-frequency oscillations, the researchers used a specialized software algorithm followed by manual validation to ensure accuracy. They also tracked whether the brain waves were more prominent in one hemisphere than the other—a pattern that might signal underlying pathology.
The results showed that participants with Alzheimer’s disease had more high-frequency oscillations than healthy controls across many brain areas, especially in the right temporal and occipital lobes. Surprisingly, those without any signs of epileptic activity had even more high-frequency oscillations in some regions than those with epileptic activity. This finding suggests that high-frequency oscillations might not only reflect seizure risk but could also point to broader forms of brain hyperexcitability linked to Alzheimer’s itself.
When the team compared the effects of levetiracetam on brain activity, they found notable differences between the two Alzheimer’s subgroups. In patients with epileptic activity, levetiracetam reduced high-frequency oscillations in several brain regions, particularly in the frontal and occipital lobes. This suggests that the drug helped calm overactive brain networks that may be tied to silent seizures. In contrast, in patients without detectable epileptic activity, levetiracetam unexpectedly increased the rate of high-frequency oscillations in areas like the parietal and central regions.
“Brain rhythm abnormalities are a common feature of dementia, but they have not been explored thoroughly,” Vossel told PsyPost. “We found that high-frequency oscillations are increased in the brains of Alzheimer’s patients, which indicates over-excitation of neurons. In Alzheimer’s patients with epileptic activity, antiseizure medications reduced high-frequency oscillations and were associated with cognitive improvements, showing a potential therapeutic benefit.”
The researchers also observed asymmetry in the distribution of high-frequency oscillations. In patients with epileptic activity, high-frequency oscillations were more concentrated in the right hemisphere, especially in the temporal and occipital lobes. This pattern was not seen in patients without epileptic activity, further indicating that asymmetric high-frequency oscillations might be a signature of epilepsy-related hyperexcitability in Alzheimer’s disease.
“We were surprised to see increased high-frequency oscillations in Alzheimer’s patients who had no history of epilepsy or epileptic activity,” Vossel said. “This indicates that high-frequency oscillations are a general feature of Alzheimer’s disease. However, high-frequency oscillations were more asymmetric in Alzheimer’s patients with epileptic activity and appear to be more pathological when occurring on one side of the brain.”
These findings are consistent with previous research in animal models showing increased high-frequency oscillations in Alzheimer’s and epilepsy. However, the current study is the first to report these fast brain rhythms in Alzheimer’s patients using non-invasive MEG scans. The presence of high-frequency oscillations, particularly when unevenly distributed across the brain, may provide an important window into disease progression and treatment response.
While the results are promising, the study does have some limitations. The control group was older than the Alzheimer’s group, which could affect comparisons. Also, the MEG data were sometimes noisy, and the sample size was relatively small. The study focused only on white, non-Hispanic participants, so the findings may not apply to more diverse populations. Longer and more detailed recordings may help future studies better understand how high-frequency oscillations change across sleep and waking states and how they relate to different types of Alzheimer’s pathology.
“MEG recordings are a sensitive method to detect brain rhythm abnormalities in dementia, but can only detect high-frequency oscillations produced by large populations of neurons,” Vossel noted. “As a result, MEG may miss high-frequency oscillations arising from small, localized brain regions.”
This research adds to a growing body of evidence that abnormal electrical activity plays a larger role in Alzheimer’s disease than previously recognized. Identifying high-frequency oscillations as a potential biomarker opens up new avenues for diagnosing and managing the disease. The fact that levetiracetam reduced high-frequency oscillations in patients with subclinical seizures but increased them in others suggests that treatments might need to be tailored depending on the individual’s brain activity patterns.
Future research could explore whether high-frequency oscillations appear in the early stages of Alzheimer’s or in other neurodegenerative conditions. Combining MEG with other imaging techniques, like intracranial recordings or advanced brain scans, might offer a clearer picture of where and how these brain waves arise. Understanding the specific neural circuits involved in generating high-frequency oscillations may also help clarify their role in memory, attention, and cognitive decline.
“We are exploring other features from MEG recordings to enable more efficient, cost-effective tools to identify and treat epilepsy in Alzheimer’s disease,” Vossel added. “We are deeply grateful to the many research participants for their generous time and effort. As research into brain rhythm abnormalities in dementia advances, we believe brain rhythm recordings will play an increasingly valuable role in dementia evaluations – much like how extended heart recordings are routinely used to assess cardiac function.”
The study, “High-frequency oscillations in epileptic and non-epileptic Alzheimer’s disease patients and the differential effect of levetiracetam on the oscillations,” was authored by M. C. Vishnu Shandilya, Kwaku Addo-Osafo, Kamalini G. Ranasinghe, Mohamad Shamas, Richard Staba, Srikantan S. Nagarajan, and Keith Vossel
