The miracle of memory is that events of the past can live again. The brain retrieves images and words both vital and trivial: the face and voice of a loved one, the sights and sounds of a childhood walk in the park, the shelf holding jars of olives in the supermarket or a scrap of passing conversation.
But age and disease can eat away at memory, both in the short- and long-term, diminishing the brain’s ability to recall and removing threads from the tapestry of life.
One of those conditions is epilepsy. The electrical storms in the brain that contribute to various kinds of seizures can rob individuals of blocks of time forever. In some cases, chronic seizures can impair the brain’s memory-making permanently.
But is it possible to prod the brain to remember better? That is the subject of a study recently begun at the University of Colorado – Anschutz Medical Campus. The multi-center trial, funded by the National Institute of Neurological Disorders and Stroke, tests whether timed pulses of electrical stimulation, delivered to targeted areas of the brain, could improve a person’s ability to store and retrieve the elements that are the stuff of memory.
The connection between epilepsy and memory loss
Dr. Aaron Geller, assistant professor in the Department of Neurology at the University of Colorado School of Medicine, leads the study at CU. He noted that “epilepsy and memory intersect in multiple ways.” For example, tonic-clonic seizures (often called grand mal) nearly always interfere with memory, simply because they can render a person unconscious, he said.
Focal onset impaired awareness seizures (or partial complex), which affect a small area of the brain, can cause relatively brief periods of unawareness that also contribute to memory loss. These seizures create abnormal brain rhythms that disrupt areas “critical for being conscious and processing the flow of information,” Geller said. The result is a “temporary disruption in forming new memories.”
Finally, epilepsy can cause long-term memory loss in people who suffer seizures in the brain’s temporal lobe, a frequent site of attacks. The temporal lobe lies near the hippocampus – the brain’s “most important memory circuitry,” Geller said. Repeated seizures in this area can cause brain damage that wipes away memories over an extended period of time.
Analyzing brain activity in medication-resistant epilepsy patients
The memory study’s subjects are those for whom anti-seizure medications have been ineffective – about one-third of all epilepsy patients, Geller said. The patients are enrolled in a separate surgical plan that requires intracranial electroencephalography (EEG) monitoring. The procedure involves drilling holes through the skull and placing electrodes on or in the brain. The aim: detect and monitor brain waves – the signs of the electrical weather in the brain.
Patients then spend extended time in the epilepsy monitoring unit, where a team records and maps their brain activity. The aim: pinpoint areas of the brain where seizures occur. That information serves as a guide for surgeons to remove the tissue that drives the electrical storms of epilepsy.
“If the tissue is in an area critical for functions like speech or movement, and therefore cannot be removed, treatment with an implanted neurostimulator device may be possible,” Geller said. For example, the FDA-approved NeuroPace device tracks brain waves in people with epilepsy and delivers targeted stimulation when brain activity signals a seizure.
Rather than surgical planning, Geller and other memory study researchers aim to use the electrical mapping to scrutinize the brain waves that may pinpoint areas of diminished memory power. The hypothesis – grounded in studies previously conducted at the University of Pennsylvania – is that low-performing memory areas of the brain can be improved with electrical stimulation – a “nudge,” as Geller puts it.
Geller’s research team observes the patient’s brain rhythms during memory tests while they undergo EEG monitoring. The first tests occur without any stimulation. The team analyzes that data to build a computer model, based on the rhythms, that predicts whether the patient is in “high-performance or low-performance memory states,” Geller said.
Searching for memory markers
How does the computer do that? Geller said the computer looks for “biomarkers” of memory performance – that is, bits of electrical information extracted from the “peaks and troughs” of brain activity that appear as rising and falling lines on a screen or sheet of paper. Just as a protein or other physical substance can be a biomarker of cancer, so too might brain wave patterns be a signal of high or low memory performance, Geller said.
During several days of memory tests involving pictures, words, and stories, the computer analyzes the brain waves it receives from patients and controls the electrical stimulation it delivers. During the test, if the patient’s brainwaves predict a low-performing memory state, the computer sends the stimulating electrical nudge that could produce improvements.
The hope is that repeated tests will help improve knowledge of both the biomarkers that define healthy memory storage and retrieval and of the specific regions of the brain that might benefit from stimulation, Geller said.
An unexpected struggle with epilepsy
Katy Thomas was the first patient enrolled in Geller’s trial. Her participation is only one piece of a complex battle with epilepsy that she hopes will resolve in the coming weeks and months.
Her struggle began in 2017. Her husband, Geoff, was startled when he walked into the kitchen of their house in Firestone and saw Katy sprawled unconscious on the floor. The incident was not only frightening but also mysterious because she had no memory of what had happened.
Katy received CT and MRI scans of the brain that indicated she had had an epileptic seizure, which was quite a surprise. She was 38 and had experienced “no signs or symptoms” of epilepsy until the kitchen attack.
Two years of a changing regimen of anti-seizure medications followed, during which Katy worked and she and Geoff raised their three boys, Sam, Jack and Luke, now 15, 12 and 10, respectively. But one morning in 2019, her epilepsy took a nearly deadly turn.
Heeding the danger signs of epilepsy
The kids had asked for doughnuts, so Katy hopped in the car alone to make a short drive to a shop in neighboring Dacono to get some. She put the box of donuts in the car and began backing out of the parking lot. The next thing she knew, she was being hoisted into an ambulance.
The incident was a void in her mind. She learned at the hospital that she’d lost consciousness shortly after putting the car in reverse. Without her control, the car rolled down an embankment to a green belt, flipped over and was totaled. Fortunately, she did not hit a person or another car.
Katy was only slightly injured in the mishap, but the accident was a turning point for her. She immediately turned over her driver’s license and was determined to find a more effective treatment for her epilepsy.
“I said, ‘I am not going to risk my life or anybody else’s life or property,”’ Katy said. “The accident was a wake-up call that this is more serious than taking medications and trying to deal with [epilepsy]. We need to figure this out to have a better quality of life and function the way I want to.”
Surgery to remove the seizure-prone tissue in the brain
After the accident, Katy began work with UCHealth epilepsy specialist Dr. Jacob Pellinen, who tried, ultimately without success, to control her seizures with different combinations of medications. She opted for more testing, including MRI and CT scans; a neuropsychological evaluation to track her memory, speech and motor functions; and finally, the EEG procedure and 10-day stay in the epilepsy monitoring unit that included her participation in Geller’s memory study.
During her stint in the monitoring unit, Katy had some 18 seizures – obviously unpleasant, but a gold mine of electrical evidence about her epilepsy. The activity revealed that Katy’s seizures originate in the right anterior temporal lobe of the brain, the most common site for the focal onset impaired awareness seizures that plague her with bouts of disconnection from her surroundings, including loss of consciousness.
A 10-person board that included Pellinen, her neurologist, Dr. Richard Gross and neurosurgeon Dr. Steven Ojemann unanimously recommended that surgery to remove the seizure-prone tissue in her brain would give her the best chance for a seizure-free recovery. She agreed and underwent the procedure successfully on March 2. She said she was scared but also determined that surgery was her best chance to free herself from the tyranny of her epilepsy.
“I’ve got boys to take care of and a life to live with my husband and my best friends,” Katy said. “I’m still young and have things I want to do. I’m sick of being sick.”
A chance to understand memory loss and epilepsy
She also hopes the surgery will improve the memory loss that is part of epilepsy’s burden.
“The biggest change is in my short-term memory, which is just awful,” Katy said. “I don’t remember things the children have said. I’m constantly writing notes and setting alarms and reminders on my phone.” People she met a month ago quickly become distant memories.
She consented to join Geller’s study to advance knowledge about epilepsy.
“I did it because there is no reason not to,” Katy said. “If it benefits other people and others can learn from it, then that’s great for me. The study made me feel proud that I was doing something to help in the field of epilepsy.”
Geller said the study points to the possible future of epilepsy treatment. For example, knowledge gleaned from it could advance development of an implantable “neuroprosthetic system” that boosts memory with timed electrical stimulation to specific parts of the brain, an approach similar to the NeuroPace device.
Memory-boosting technology could also help people who don’t suffer from epilepsy, Geller added.
“We know the U.S. population is aging,” he said. “As we do, memory will become an increasingly big factor that affects quality of life. A memory stimulation system has the potential to improve the lives of a huge number of people. In principle, this trial is about improving memory for everyone.”
For more information about the trial, contact Neurology Research: [email protected] or 303-724-4644.