An area of the brain known as the amygdala may be critical in the conscious control of breathing, making it an important target area for research into epilepsy-related sudden death, according to a study recently published by CURE Grantee Dr. William Nobis of Northwestern University Feinberg School of Medicine.1 As part of a team led by Dr. Christina Zelano, also of Northwestern University, Dr. Nobis found that stimulation of the amygdala consistently induced apnea, or disrupted breathing, in a group of individuals with temporal lobe epilepsy. This finding is significant because it points to a possible role of the amygdala in what may be the most severe epilepsy-related complication, Sudden Unexpected Death in Epilepsy (SUDEP).
SUDEP occurs when a seemingly healthy person with epilepsy dies for no obvious reason,2 most often at night or during sleep. While research suggests that several factors including respiratory and cardiac dysfunction contribute to SUDEP,3,4 the precise biological processes remain unknown. By implanting electrodes into the brains of seven patients undergoing surgical evaluation for temporal lobe epilepsy, Dr. Nobis and his team were able to pinpoint specific regions of the amygdala that are important in controlling respiration, identifying areas possibly important in the cessation of respiration that characterizes SUDEP. Furthermore, the team found that by instructing patients to inhale during an apnea-inducing stimulation of the amygdala, they were able to prevent apnea providing an area upon which to focus development of therapeutic strategies to prevent SUDEP.
With funding from CURE, Dr. Nobis is now pushing this research to uncover the mechanisms behind SUDEP even further. He and his team think that the amygdala may be activated during seizures, causing it to lead to cessation of respiration and SUDEP. By using a genetic animal model of epilepsy that has a high rate of SUDEP, the team hopes to identify and examine the specific neurons within the amygdala that project to important respiratory centers in other parts of the brain, allowing the amygdala to influence respiratory function – and the loss of respiratory function that occurs in SUDEP.
Early results from Dr. Nobis’s current CURE project have begun to identify populations of neurons in the amygdala that project to areas of the brain important in respiration. The team next plans on examining how these neurons are activated in response to seizures, and how changes in the excitability of these neurons might correspond with changes in respiratory function that could lead to SUDEP.
In the future, Dr. Nobis hopes to be able to determine whether it is possible to target this subset of neurons within the amygdala to prevent SUDEP from occurring, providing a large step forward for SUDEP research and possible therapies for SUDEP prevention. Thanks to CURE-funded researchers like Dr. Nobis, we are moving closer to being able to eliminate the sudden and devastating death of individuals with epilepsy.
1 Nobis WP et al. Amygdala-stimulation-induced apnea is attention and nasal-breathing dependent. Ann Neurol 2018; 83(3):460-471.
2 Nashef. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38(11 Suppl):S6-8.
3 Surges et al. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol 2009; 5(9):492-504.
4 Bagnall et al. Genetic basis of sudden unexpected death in epilepsy. Front Neurol 2017; 8:348.