Increasing Mitochondrial Respiration as a Novel Mechanism for Cognitive Augmentation

The Gonzalez‐Lima Laboratory at the University of Texas at Austin is recruitingparticipants for a research study. The study examines whether a combined treatment canimprove cognitive function. The treatment includes transcranial photobiomodulation(tPBM), a form of light therapy applied to the forehead, along with a dietary supplement.The treatment targets an enzyme called cytochrome‐c‐oxidase, which plays a key role inhow the mitochondria inside brain cells use oxygen to produce energy. As people age, thisprocess often becomes less efficient, contributing to cognitive decline seen in normalaging and in neurodegenerative diseases. The hypothesis is that improving mitochondrialfunction and cytochrome‐c‐oxidase activity will boost neuronal energy production andreduce oxidative stress, ultimately enhancing cognitive performance. Previous studiesfrom the Gonzalez‐Lima Lab found that applying tPBM to the prefrontal cortex improvesbrain metabolic activity and enhances cognitive functions such as attention, memory, andexecutive function. The dietary supplement provides an alternative energy source derivedfrom ketones, which mitochondria can use for oxygen metabolism. This may help bypass theimpaired glucose metabolism often seen in aging brains, potentially leading to furthercognitive improvements. This study will investigate the cognitive effects of thiscombined treatment in adults ages 18 to 85. During the first visit to the lab,participants will complete informed consent, health questionnaires, and cognitiveassessments, and wear sensors on the head which monitor brain activity. They will also betrained to use a headset device which uses light‐emitting diodes (LEDs) to deliver lightto the forehead. They will be given daily supplements and instructed on how to maintain adaily log for at‐home treatments. Then, for the next two months, participants willcomplete the daily protocol at home. Weekly check‐ins will monitor progress throughoutthis period. After two months, participants will return to repeat the assessments fromthe first visit and return their study materials. Participants will receive $200 uponcompleting the study, and parking expenses will be reimbursed for each visit. Briefly,one aim will be to map the relationship between baseline prefrontal functionalconnectivity and dimensional performance in cognitive control and affective processing.Another aim will be to evaluate mechanistic efficacy of chronic tPBM in engagingprefrontal circuits and restoring task‐based behavioral performance. A final aim is tomodel the longitudinal relationship between prefrontal circuit health and real‐worldsleep, circadian stability, and neuroendocrine regulation. By focusing on target‐drivenbiobehavioral mechanisms, this study aims to identify novel therapeutic targets andestablish scalable biomarker pipelines.