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HomeHealthResearch Investigates Seizure Risks Associated with Thalamic Stimulation

Research Investigates Seizure Risks Associated with Thalamic Stimulation

In experiments with awake mice, scientists discovered that even minimal levels of deep brain stimulation applied to the central thalamus could sometimes trigger electrographic seizures.
Increasing interest has emerged among researchers and healthcare professionals in electrically stimulating a brain area known as the central thalamus. This technique can help bring individuals out of unconscious states due to traumatic brain injuries or anesthesia and enhance cognitive abilities and performance in awake animals. However, this procedure, termed CT-DBS, can occasionally result in seizures. A new study conducted by researchers at MIT and Massachusetts General Hospital (MGH) has explored this method in awake mice, measuring the likelihood of seizures at various stimulation levels and highlighting that they can occur even at low intensities.

“It is crucial to comprehend the development and occurrence of these seizure types, especially as brain stimulation therapies are increasingly adopted,” stated co-senior author Emery N. Brown, who holds the Edward Hood Taplin Professorship in Medical Engineering and Computational Neuroscience at The Picower Institute for Learning and Memory and various departments at MIT.

Within the brain, the seizures linked to CT-DBS manifest as “electrographic seizures,” which involve voltage spikes among neurons across a wide range of frequencies. Behaviorally, they appear as “absence seizures,” during which the subject exhibits a vacant stare and remains still for approximately 10-20 seconds.

The aim of this study was to identify a safe CT-DBS stimulation current—specifically under 200 microamps—where seizures could be reliably avoided.

To find this ideal stimulation level, the researchers devised a protocol that began with short sessions of CT-DBS at 1 microamp, then gradually increased the current up to 200 microamps until they observed a threshold where an electrographic seizure was triggered. After establishing this threshold, they conducted longer stimulation sessions at the lower current level to see if seizures could be avoided. This process was repeated with various stimulation frequencies. Surprisingly, they found that electrographic seizures still occurred 2.2 percent of the time during these longer tests (22 occurrences out of 996 tests) and affected 10 out of 12 mice. Even at 20 microamps, seizures were noted in 3 out of 244 trials, yielding a 1.2 percent incidence rate.

“It was essential to report this finding, as it was quite unexpected,” remarked co-lead author Francisco Flores, a research affiliate at The Picower Institute and CBMM, also an instructor in anesthesiology at MGH, where Brown practices anesthesiology. The study, published in Brain Stimulation, was co-led by Isabella Dalla Betta, a technical associate at The Picower Institute.

The frequency of stimulation did not influence the risk of seizures; however, the likelihood of electrographic seizures increased with the current. For example, seizures were observed in 5 out of 190 trials at 50 microamps and in 2 out of 65 trials at 100 microamps. The researchers also noted that seizures occurred more swiftly at higher stimulation currents. Furthermore, they found that stimulating the thalamus on both sides of the brain resulted in quicker seizure onset compared to stimulation on only one side. While some mice displayed behaviors akin to absence seizures, others became hyperactive.

The reason some mice experienced electrographic seizures at just 20 microamps while two mice did not show seizures at 200 microamps remains unclear. Flores hypothesized that varying brain states could influence susceptibility to seizures triggered by thalamic stimulation. It is noteworthy that seizures are typically not observed in humans receiving CT-DBS while in a minimally conscious state after traumatic brain injuries, nor in animals under anesthesia. Flores indicated that future studies will aim to uncover these pertinent brain states.

For now, the authors of the study emphasized the importance of closely monitoring EEG for electrographic seizures when performing CT-DBS, particularly on awake subjects.

The paper’s co-senior author is Matt Wilson, the Sherman Fairchild Professor at The Picower Institute, CBMM, and the departments of Biology and Brain and Cognitive Sciences. Alongside Dalla Betta, Flores, Brown, and Wilson, the other contributors to the study include John Tauber, David Schreier, and Emily Stephen.

Funding for this research was provided by The JPB Foundation, The Picower Institute for Learning and Memory, various individual donors, and the National Institutes of Health.