Summary: Study reveals how abnormal brain activity and memory are linked in those with epilepsy. The findings could lead to better treatments for cognitive impairment associated with epilepsy.
Source: Cedars Sinai Medical Center
A new Cedars-Sinai study reveals how memory and abnormal brain activity are linked in patients with epilepsy who often report problems with memory. The data show that abnormal electrical pulses from specific brain cells in these patients are associated with a temporary kind of memory disruption called transient cognitive impairment.
Understanding this process has the potential to lead to improvements in treating epilepsy patients, as well as contribute to knowledge of how memory works.
Epilepsy is a neurological disorder characterized by abnormal brain activity that can cause seizures. It affects about 3.4 million Americans, or 1% of the population, according to the federal Centers for Disease Control and Prevention.
“To our knowledge, our study is the first to investigate the actual mechanism of transient cognitive impairment in epilepsy,” said Ueli Rutishauser, PhD, associate professor in the Department of Neurosurgery at Cedars-Sinai. He was senior author of the study, published online in the Journal of Neuroscience.
To perform their study, Rutishauser and his team investigated electrical activity in the hippocampus, an area of the brain known to be important for memory. Using electrodes implanted in the brains of 11 adult epilepsy patients as part of their treatment, the team recorded activity of individual cells in the hippocampus during a recognition memory task.
Patients were first shown 100 new images. Later, a subset of 50 of these images were repeated a second time randomly intermixed with other new images. After each image, patients were asked whether they had seen the image before and how sure they were about their answer.
Results showed that abnormal electrical pulses in the brain, known as interictal epileptiform discharges (IEDs), temporarily changed the firing of individual cells in the hippocampus. This change in the activity of the cells in turn disrupted the patients’ ability to recall whether they previously had seen a presented image. Epilepsy patients commonly experience IEDs between seizures and report transitive cognitive impairment. However, it has so far remained unknown why IEDs cause such impairment.
During the task, the extent of memory disruption was related to exactly when an IED occurred, with the most severe impairment caused by IEDs that appeared within two seconds of the patient trying to recall an image, Rutishauser said. He added that the effect was specific to recall and that the presence of IEDs did not disrupt the encoding of new memories.
The study’s first author, Chrystal Reed, MD, PhD, assistant professor of Neurology at Cedars-Sinai, said the findings are important because understanding how and why memory impairments occur can help develop treatment options to improve the quality of life for epilepsy patients.
“The unpredictability of seizures and memory impairment is a major stressor in people who have epilepsy,” Reed said.
The study’s co-authors were Adam Mamelak, MD, professor of Neurosurgery; Nand Chandravadia, research associate in Rutishauser’s laboratory; Jeffrey Chung, MD, assistant professor of Neurology; and Clayton Mosher, PhD, postdoctoral fellow in Rutishauser’s laboratory.
Funding: Research reported in this publication was supported by the National Institutes of Health under award numbers R01MH110831 and U01NS103792.
Source:
Cedars Sinai Medical Center
Media Contacts:
Jane Engle – Cedars Sinai Medical Center
Image Source:
The image is in the public domain.
Original Research: Closed access
“Extent of single-neuron activity modulation by hippocampal interictal discharges predicts declarative memory disruption in humans”. Chrystal M. Reed, Clayton P. Mosher, Nand Chandravadia, Jeffrey M. Chung, Adam N. Mamelak and Ueli Rutishauser.
Journal of Neuroscience doi:10.1523/JNEUROSCI.1380-19.2019.
Abstract
Extent of single-neuron activity modulation by hippocampal interictal discharges predicts declarative memory disruption in humans
Memory deficits are common in epilepsy patients. In these patients, the interictal electroencephalography commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically-refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50/728 neurons were significantly modulated by IEDs, with the strongest modulation in the MTL (33/416) and in particular the right hippocampus (12/58). Putative inhibitory neurons, as identified by their extracellular signature, where more likely to be modulated by IEDs than putative excitatory neurons (19/157 vs. 31/571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, this data links the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt MTL-dependent declarative memory retrieval processes.
SIGNIFICANCE STATEMENT
Interictal epileptiform discharges (IEDs) are thought to be a cause of memory deficits in chronic epilepsy patients, but the underlying mechanisms are not understood. Utilizing single-neuron recordings in epilepsy patients, we found that hippocampal IEDs transiently change firing of hippocampal neurons and disrupted selectively the retrieval, but not encoding, of declarative memories. The extent of the modulation of the individual firing of hippocampal neurons by an IED predicted the extent of reduction of subjective retrieval confidence. Together, this data reveal a specific kind of transient cognitive impairment caused by IEDs and link this impairment to the modulation of the activity of individual neurons. Understanding the mechanisms by which IEDs impact memory is critical for understanding memory impairments in epilepsy patients.
