In animal models, even low stimulation currents can sometimes still cause electrographic seizures, researchers found.
David Orenstein | The Picower Institute for Learning and Memory
The idea of electrically stimulating a brain region called the central thalamus has gained traction among researchers and clinicians because it can help arouse subjects from unconscious states induced by traumatic brain injury or anesthesia, and can boost cognition and performance in awake animals. But the method, called CT-DBS, can have a side effect: seizures. A new study by researchers at MIT and Massachusetts General Hospital (MGH) who were testing the method in awake mice quantifies the probability of seizures at different stimulation currents and cautions that they sometimes occurred even at low levels.
“Understanding production and prevalence of this type of seizure activity is important because brain stimulation-based therapies are becoming more widely used,” says co-senior author Emery N. Brown, Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience in The Picower Institute for Learning and Memory, the Institute for Medical Engineering and Science, the Department of Brain and Cognitive Sciences, and the Center for Brains Minds and Machines (CBMM) at MIT.
In the brain, the seizures associated with CT-DBS occur as “electrographic seizures,” which are bursts of voltage among neurons across a broad spectrum of frequencies. Behaviorally, they manifest as “absence seizures” in which the subject appears to take on a blank stare and freezes for about 10-20 seconds.
In their study, the researchers were hoping to determine a CT-DBS stimulation current — in a clinically relevant range of under 200 microamps — below which seizures could be reliably avoided.
In search of that ideal current, they developed a protocol of starting brief bouts of CT-DBS at 1 microamp and then incrementally ramping the current up to 200 microamps until they found a threshold where an electrographic seizure occurred. Once they found that threshold, then they tested a longer bout of stimulation at the next lowest current level in hopes that an electrographic seizure wouldn’t occur. They did this for a variety of different stimulation frequencies. To their surprise, electrographic seizures still occurred 2.2 percent of the time during those longer stimulation trials (i.e. 22 times out of 996 tests) and in 10 out of 12 mice. At just 20 microamps, mice still experienced seizures in three out of 244 tests, a 1.2 percent rate.
“This is something that we needed to report because this was really surprising,” says co-lead author Francisco Flores, a research affiliate in The Picower Institute and CBMM, and an instructor in anesthesiology at MGH, where Brown is also an anesthesiologist. Isabella Dalla Betta, a technical associate in The Picower Institute, co-led the study published in Brain Stimulation.
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