Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation

BackgroundConverging evidence suggests that bipolar disorder (BD) involves mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism associated with cognitive impairment, which persists in remitted BD individuals. Transcranial infrared laser stimulation (TILS) provides safe, non-invasive...

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Main Authors: Douglas W. Barrett, Roger E. Davis, Jennifer E. Siegel-Ramsay, Amy Bichlmeier, Jorge R. C. Almeida, F. Gonzalez-Lima
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1547230/full
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author Douglas W. Barrett
Roger E. Davis
Jennifer E. Siegel-Ramsay
Amy Bichlmeier
Jorge R. C. Almeida
F. Gonzalez-Lima
author_facet Douglas W. Barrett
Roger E. Davis
Jennifer E. Siegel-Ramsay
Amy Bichlmeier
Jorge R. C. Almeida
F. Gonzalez-Lima
author_sort Douglas W. Barrett
collection DOAJ
description BackgroundConverging evidence suggests that bipolar disorder (BD) involves mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism associated with cognitive impairment, which persists in remitted BD individuals. Transcranial infrared laser stimulation (TILS) provides safe, non-invasive brain stimulation that enhances PFC metabolism via photobiomodulation of mitochondrial respiration and tissue oxygenation. We tested the hypothesis that the neurocognitive deficits found in BD may be ameliorated by TILS treatments.MethodsThis is the first study to explore neurocognitive effects of repeated TILS administration in BD. Using an open-label design, 29 individuals with remitted BD received six weekly TILS treatments. Working memory and attention were assessed with trail-making and 2-back tasks sensitive to TILS cognitive effects in individuals with BD. Changes in PFC network interactions were measured with functional near-infrared spectroscopy (fNIRS) because this method can measure TILS effects on oxygen metabolism in the PFC of individuals with BD.ResultsParticipants reported no adverse effects from treatment, confirming the safety of this intervention in individuals with BD. Cognitive test results showed that in people with remitted BD, TILS was effective at improving cognition, i.e., enhanced speed and accuracy in tasks reflecting cognitive flexibility, working memory, and attentional control. Antipsychotic medication improved TILS cognitive effects. The fNIRS results showed a significant reduction in PFC network correlations of oxygenated hemoglobin changes driven by cognitive task performance. The right-hemisphere frontopolar cortex showed greater TILS effects than its left-hemisphere counterpart.ConclusionsRepeated TILS is a safe intervention to improve cognition in people with remitted BD. Continued antipsychotic medication may have contributed to the cognitive improvement. To confirm TILS efficacy, a sham-controlled, double-blinded randomized trial is needed.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05354895.
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spelling doaj-art-0e9909de00624859ae35656c1a970d642025-01-30T12:18:21ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-01-011610.3389/fpsyt.2025.15472301547230Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulationDouglas W. Barrett0Roger E. Davis1Jennifer E. Siegel-Ramsay2Amy Bichlmeier3Jorge R. C. Almeida4F. Gonzalez-Lima5Departments of Psychology, Psychiatry and Behavioral Sciences, and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, United StatesDepartments of Psychology, Psychiatry and Behavioral Sciences, and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, United StatesBipolar Disorder Center, Department of Psychiatry and Behavioral Sciences, Dell Medical School, Austin, TX, United StatesBipolar Disorder Center, Department of Psychiatry and Behavioral Sciences, Dell Medical School, Austin, TX, United StatesBipolar Disorder Center, Department of Psychiatry and Behavioral Sciences, Dell Medical School, Austin, TX, United StatesDepartments of Psychology, Psychiatry and Behavioral Sciences, and Institute for Neuroscience, The University of Texas at Austin, Austin, TX, United StatesBackgroundConverging evidence suggests that bipolar disorder (BD) involves mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism associated with cognitive impairment, which persists in remitted BD individuals. Transcranial infrared laser stimulation (TILS) provides safe, non-invasive brain stimulation that enhances PFC metabolism via photobiomodulation of mitochondrial respiration and tissue oxygenation. We tested the hypothesis that the neurocognitive deficits found in BD may be ameliorated by TILS treatments.MethodsThis is the first study to explore neurocognitive effects of repeated TILS administration in BD. Using an open-label design, 29 individuals with remitted BD received six weekly TILS treatments. Working memory and attention were assessed with trail-making and 2-back tasks sensitive to TILS cognitive effects in individuals with BD. Changes in PFC network interactions were measured with functional near-infrared spectroscopy (fNIRS) because this method can measure TILS effects on oxygen metabolism in the PFC of individuals with BD.ResultsParticipants reported no adverse effects from treatment, confirming the safety of this intervention in individuals with BD. Cognitive test results showed that in people with remitted BD, TILS was effective at improving cognition, i.e., enhanced speed and accuracy in tasks reflecting cognitive flexibility, working memory, and attentional control. Antipsychotic medication improved TILS cognitive effects. The fNIRS results showed a significant reduction in PFC network correlations of oxygenated hemoglobin changes driven by cognitive task performance. The right-hemisphere frontopolar cortex showed greater TILS effects than its left-hemisphere counterpart.ConclusionsRepeated TILS is a safe intervention to improve cognition in people with remitted BD. Continued antipsychotic medication may have contributed to the cognitive improvement. To confirm TILS efficacy, a sham-controlled, double-blinded randomized trial is needed.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05354895.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1547230/fullbipolar disordertranscranial infrared laser stimulationphotobiomodulationcognitive enhancementprefrontal cortex stimulationbrain oxygenation
spellingShingle Douglas W. Barrett
Roger E. Davis
Jennifer E. Siegel-Ramsay
Amy Bichlmeier
Jorge R. C. Almeida
F. Gonzalez-Lima
Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
Frontiers in Psychiatry
bipolar disorder
transcranial infrared laser stimulation
photobiomodulation
cognitive enhancement
prefrontal cortex stimulation
brain oxygenation
title Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
title_full Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
title_fullStr Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
title_full_unstemmed Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
title_short Cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
title_sort cognitive improvement and prefrontal network interactions in individuals with remitted bipolar disorder after transcranial infrared laser stimulation
topic bipolar disorder
transcranial infrared laser stimulation
photobiomodulation
cognitive enhancement
prefrontal cortex stimulation
brain oxygenation
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1547230/full
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