Behavioral Deficits and Cortical Network Dysfunction Following Repeated Mild Traumatic Brain Injuries

Natalie J Pinkowski; Brandi R Hess; Johann M Pacheco; Devon S Hatcher; Myah McDonald; Adrienne N Swindle; Raycarlo Laboy Ramirez; Matthew Situ; Taha Abdeljawad; Carissa J Mehos; Andrew R Mayer; Sam McKenzie; Russell A Morton

doi:10.1177/08977151261425217

Behavioral Deficits and Cortical Network Dysfunction Following Repeated Mild Traumatic Brain Injuries

J Neurotrauma. 2026 Mar 14:8977151261425217. doi: 10.1177/08977151261425217. Online ahead of print.

Authors

Natalie J Pinkowski^{1

2

3}, Brandi R Hess^{1

2}, Johann M Pacheco^{1

2

4}, Devon S Hatcher^{1

2}, Myah McDonald^{1

2}, Adrienne N Swindle^{1

2}, Raycarlo Laboy Ramirez^{1

2}, Matthew Situ^{1

2}, Taha Abdeljawad^{1

2}, Carissa J Mehos^{1

2}, Andrew R Mayer^{5

6

7

8}, Sam McKenzie^{1

2}, Russell A Morton^{1

2}

Affiliations

¹ Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
² Center for Brain Recovery and Repair, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
³ Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁴ Department of Neurology, Thomas Jefferson, Sidney Kimmel Medical College, Philadelphia, Pennsylvania, USA.
⁵ Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico, USA.
⁶ Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
⁷ Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
⁸ Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA.

Abstract

Mild traumatic brain injury (mTBI) is a prevalent health concern, with more than 2.5 million cases occurring annually in the United States. Acute signs and symptoms of mTBIs may involve physical symptoms, as well as emotional, cognitive, and sleep-related issues. The underlying mechanisms of these symptoms remain elusive. Here, we describe that repeated closed skull mTBIs in mice are associated with acute behavioral deficits. We found that optogenetic-induced spreading depolarizations (SDs) are associated with similar behavioral deficits. Using in vivo electrophysiology, we confirmed the depression of cortical network activity following optogenetic-induced SDs. The timing of the high-frequency activity recovery coincided with the recovery of voluntary movement. Following the depression, there was a prolonged period of increased power in low frequencies (<30 Hz). Cortical dysfunction coincided temporally with motor behavioral deficits in the neurological severity score tasks. Our study provides evidence that repeated mTBIs or SDs are associated with worse behavioral deficits.

Keywords: behavioral assessment; electrophysiology; vascular reactivity.

Abstract

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