AUTHOR=Martin Paula I. , Chao Linda , Krengel Maxine H. , Ho Michael D. , Yee Megan , Lew Robert , Knight Jeffrey , Hamblin Michael R. , Naeser Margaret A. 

TITLE=Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.574386

DOI=10.3389/fneur.2020.574386

ISSN=1664-2295

ABSTRACT=<p><bold>Introduction:</bold> Approximately 25–30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI.</p><p><bold>Materials and Methods:</bold> Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD.</p><p><bold>Results:</bold> Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (<italic>p</italic> &lt; 0.01); and a trend for Trails 4, Number/Letter Sequencing (<italic>p</italic> &lt; 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (<italic>p</italic> &lt; 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed.</p><p><bold>Conclusion:</bold> This study was underpowered (<italic>n</italic> = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</ext-link>, identifier: NCT01782378.</p>