Electrographic seizures during low-current thalamic deep brain stimulation in mice

Francisco J Flores; Isabella Dalla Betta; John Tauber; David R Schreier; Emily P Stephen; Matthew A Wilson; Emery N Brown

doi:10.1016/j.brs.2024.08.002

Electrographic seizures during low-current thalamic deep brain stimulation in mice

Brain Stimul. 2024 Sep-Oct;17(5):975-979. doi: 10.1016/j.brs.2024.08.002. Epub 2024 Aug 10.

Authors

Francisco J Flores¹, Isabella Dalla Betta², John Tauber³, David R Schreier⁴, Emily P Stephen⁵, Matthew A Wilson⁶, Emery N Brown⁷

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, 02114, MA, USA; Center for Brains, Minds, and Machines, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA; Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA. Electronic address: fflores@mgh.harvard.edu.
² Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, 02114, MA, USA; Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA. Electronic address: idallabe@mit.edu.
³ Department of Mathematics and Statistics, Boston University, 665 Commonwealth Ave, Boston, 02215, MA, USA. Electronic address: jtauber@bu.edu.
⁴ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, 02114, MA, USA; Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 101 Merrimac St, Boston, 02114, MA, USA; Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse 16, Bern, 3010, Switzerland. Electronic address: dschreier@mgh.harvard.edu.
⁵ Department of Mathematics and Statistics, Boston University, 665 Commonwealth Ave, Boston, 02215, MA, USA. Electronic address: estephen@bu.edu.
⁶ Center for Brains, Minds, and Machines, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA; Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA. Electronic address: mwilson@mit.edu.
⁷ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, 02114, MA, USA; Center for Brains, Minds, and Machines, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA; Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, 02139, MA, USA; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, 45 Carleton St, Cambridge, 02142, MA, USA. Electronic address: enbrown@neurostat.mit.edu.

Abstract

Background: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT).

Objectives: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice.

Methods: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration.

Results: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 μA.

Conclusion: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings.

Keywords: Deep-brain stimulation; Electric stimulation; Electroencephalography; Seizure; Thalamus.

MeSH terms

Animals
Deep Brain Stimulation* / methods
Electroencephalography*
Male
Mice
Mice, Inbred C57BL
Seizures* / physiopathology
Seizures* / therapy
Thalamus* / diagnostic imaging
Thalamus* / physiology
Thalamus* / physiopathology

Grants and funding

P01 GM118269/GM/NIGMS NIH HHS/United States