Moving back in the brain to drive the field forward: Targeting neurostimulation to different brain regions in animal models of depression and neurodegeneration

Michelle R Madore; Eugenia Poh; Samuel John Bollard; Jesus Rivera; Joy Taylor; Jauhtai Cheng; Eric Booth; Monica Nable; Alesha Heath; Jerry Yesavage; Jennifer Rodger; M Windy McNerney

doi:10.1016/j.jneumeth.2021.109261

Moving back in the brain to drive the field forward: Targeting neurostimulation to different brain regions in animal models of depression and neurodegeneration

J Neurosci Methods. 2021 Aug 1:360:109261. doi: 10.1016/j.jneumeth.2021.109261. Epub 2021 Jun 17.

Authors

Affiliations

¹ Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
² Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia.
³ Palo Alto University, Palo Alto, CA, USA.
⁴ Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Electrical and Computer Engineering, Boise State University, Boise, ID, USA.
⁶ Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: windymc@stanford.edu.

Abstract

Background: Repetitive transcranial magnetic stimulation is a promising noninvasive therapeutic tool for a variety of brain-related disorders. However, most therapeutic protocols target the anterior regions, leaving many other areas unexplored. There is a substantial therapeutic potential for stimulating various brain regions, which can be optimized in animal models.

New method: We illustrate a method that can be utilized reliably to stimulate the anterior or posterior brain in freely moving rodents. A coil support device is surgically attached onto the skull, which is used for consistent coil placement over the course of up to several weeks of stimulation sessions.

Results: Our methods provide reliable stimulation in animals without the need for restraint or sedation. We see little aversive effects of support placement and stimulation. Computational models provide evidence that moving the coil support location can be utilized to target major stimulation sites in humans and mice.

Summary of findings with this method: Animal models are key to optimizing brain stimulation parameters, but research relies on restraint or sedation for consistency in coil placement. The method described here provides a unique means for reliable targeted stimulation in freely moving animals. Research utilizing this method has uncovered changes in biochemical and animal behavioral measurements as a function of brain stimulation.

Conclusions: The majority of research on magnetic stimulation focuses on anterior regions. Given the substantial network connectivity throughout the brain, it is critical to develop a reliable method for stimulating different regions. The method described here can be utilized to better inform clinical trials about optimal treatment localization, stimulation intensity and number of treatment sessions, and provides a motivation for exploring posterior brain regions for both mice and humans.

Keywords: Alzheimer's disease; Animal models; Computational modeling; Depression; Repetitive transcranial magnetic stimulation.

Published by Elsevier B.V.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Brain*
Depression*
Mice
Models, Animal
Stereotaxic Techniques
Transcranial Magnetic Stimulation

Abstract

Publication types

MeSH terms

Grants and funding