Brain Wave Disturbances Influence Memory Recall

Theta oscillation, a type of brain wave that is interrupted in Alzheimer’s disease, appears to influence memory, according to a team led by UT Southwestern Medical Center researchers. The discoveries, published in Nature Communications, could aid researchers in developing and testing new treatments for Alzheimer’s disease, which affects millions of people worldwide and has no cure.

“We hope to use this data to refine neuromodulation strategies so that they could have a greater ability to treat Alzheimer’s disease and other degenerative brain diseases,” said study leader Bradley Lega, M.D., Associate Professor of Neurological Surgery, Neurology, and Psychiatry and an Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

Cholinergic circuits in the brain, which are networks of cells that communicate with one another via the neurotransmitter acetylcholine, are essential for memory. These circuits are abundant in the hippocampus, which acts as the brain’s memory headquarters.

Alzheimer’s disease and related dementias are characterized by disruptions in this circuitry. Cholinesterase inhibitors, one of only two medicine classes licensed to treat Alzheimer’s disease symptoms, act by boosting cholinergic pathways. However, the processes underlying how cholinergic circuits assist human memory are unknown, according to Dr. Lega.

To assist answer this question, he and colleagues at UT Southwestern and Columbia University collaborated with 12 patients at UTSW’s Epilepsy Monitoring Unit who were being evaluated before surgery to remove the damaged regions of their brains that cause seizures. Electrodes implanted in patients brains not only assist surgeons in precisely identifying seizure foci, but also provide significant information on the brain’s inner workings, according to Dr. Lega.

While the electrodes recorded brain waves, the patients completed memory tests in which they attempted to memorize and then recall as many words as they could. In separate sessions, these participants were given either scopolamine (a medication commonly used to treat motion sickness that is also known to impair memory by acting on cholinergic circuits) or saline (which has no detectable impact). To clear their brains between multiple recall tests in the same session, the volunteers worked on math problems.

Not surprisingly, scopolamine had a considerable impact on the volunteers’ capacity to recall words. Although they could recall approximately 31% of the word lists when given saline, this plummeted to approximately 10% when given scopolamine.

When the researchers examined the brain waves, they discovered that scopolamine appeared to alter theta oscillations, which are linked to memory encoding. When patients were given this medication, the intensity of their theta oscillations fell dramatically. Other aspects of these disrupted oscillations suggested that the hippocampus was unable to communicate effectively internally and with the rest of the brain. These disturbances were more evident in volunteers who had the worst memory after scopolamine, lending credence to the connection between cholinergic circuits and theta oscillations.

According to Dr. Lega, these data show that theta oscillations are one of the primary ways that cholinergic circuits alter memory. Improving the quality of theta oscillations may thus be a priority for new Alzheimer’s disease therapy. Theta oscillations could also be used as a biomarker in clinical studies to identify whether experimental medicines are beneficial.

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