New study identifies brain region that may cause sudden death in epilepsy

Researchers have made significant progress in unraveling the mysteries of SUDEP (Sudden Unexpected Death in Epilepsy), a rare but deadly complication of epilepsy. In the U.S., around 3,000 SUDEP-related deaths occur annually. While poorly controlled epilepsy is the most significant risk factor, the exact cause of SUDEP has long eluded scientists. However, mounting evidence suggests that post-seizure breathing disruptions, known as apnea, play a crucial role.

A recent study conducted by neuroscientists at the University of Iowa pinpointed a specific area within the amygdala, a part of the brain, that triggers prolonged breathing cessation even after a seizure has subsided. This groundbreaking research sheds light on a potential source of persistent apnea, closely resembling what has been observed in SUDEP cases. These findings mark a significant advancement in understanding the mechanisms behind SUDEP.

Vicky Whittemore, Ph.D., program director at the National Institute of Neurological Disorders and Stroke, emphasizes the importance of these discoveries in identifying high-risk individuals and developing preventative measures for SUDEP.

Patients help advance SUDEP research

The University of Iowa research team, with lead authors Gail Harmata, a neuroscience graduate student, and Ariane Rhone, Ph.D., a research scientist, employed a variety of techniques to delve into the brain mechanisms associated with breathing disruptions. Their investigation involved 20 patients, spanning different age groups, who were preparing for epilepsy surgery. These patients underwent the placement of intracranial electroencephalography (iEEG) electrodes in their brains as part of the surgical planning process.

By integrating data from these intracranial recordings with functional MRI brain imaging, the researchers were able to chart the impact of amygdala stimulation across multiple sites, ultimately pinpointing the specific focal site within the amygdala linked to the issue.

The study highlights that not every patient is susceptible to this phenomenon; only five of the patients experienced prolonged apnea after amygdala stimulation. Furthermore, the precise location within the amygdala proved to be crucial. Even within the same patient, stimulating one area of the amygdala resulted in temporary breathing interruptions, while stimulating a different region led to sustained apnea even after the stimulation ceased.

New brain imaging technique reveals network linked to persistent apnea

In their research, the team also introduced a novel technique known as electrical stimulation concurrent with functional MRI, enabling them to trace the brain networks associated with persistent post-seizure apnea.

Remarkably, during the experiment, the patients remained completely unaware of their interrupted breathing. They didn’t experience the typical sensations of breathlessness or the “air hunger” that would normally trigger deep breaths.

Brian Dlouhy, a member of the Iowa Neuroscience Institute, explains that the stimulation of specific amygdala sites not only persistently inhibited breathing but also suppressed the usual alarms and air hunger responses associated with not breathing. This innovative technique allowed the researchers to explore the broader circuitry effects of stimulating one brain site, offering insights into how it influences other areas.

The brain circuitry unveiled through these experiments indicated that amygdala stimulation reduced activity in the brainstem, a critical region for breathing control and carbon dioxide sensing. Normally, elevated carbon dioxide levels prompt deep breathing, but the amygdala stimulation disrupted this response, suggesting a disruption in chemo-sensing in these patients. The studies also revealed altered activity in another brain region, the insula, which plays a role in air hunger.

Dlouhy is enthusiastic about these findings and anticipates that they will enhance our understanding of SUDEP, potentially aiding in the identification of at-risk patients and even leading to clinical trials for SUDEP prevention.

“We’re narrowing down our focus to the amygdala, which is essential if we want to translate this into therapeutic or preventive strategies,” he notes.

Source: University of Iowa

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