Transcranial Photobiomodulation on Language and Cognitive Performance in Down Syndrome: A Pilot Randomized Sham-Controlled Trial

Background: Down syndrome (DS) is associated with persistent language and cognitive impairments and with abnormalities in cortical oscillatory activity, including in the gamma range. Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulatory intervention with potential benefits for cortical physiology, language, and cognition. Methods: We conducted a pilot randomized, double-blind, sham-controlled trial of repeated 40-Hz near-infrared tPBM in adolescents and young adults with DS. Fourteen participants were randomized 1:1 to active tPBM or sham and received 18 sessions over 6 weeks, followed by short-term and long-term follow-up. Outcomes included resting-state EEG gamma power, connected-speech measures, language and cognitive indices, and selected computerized tasks. Results: Active tPBM did not significantly increase global resting-state EEG gamma power relative to sham at either follow-up. Pre-registered analyses did not show broad treatment benefit across outcomes, although they did identify a significant short-term advantage for active tPBM on grammatical morpheme accuracy in connected speech; in contrast, picture naming favored sham at long-term follow-up. Exploratory mechanistic analyses did not show a robust biological treatment signal. Both active and sham procedures were well tolerated, with no serious adverse events. Conclusions: In this underpowered pilot sample, 6 weeks of 40-Hz near-infrared tPBM--delivered unilaterally, at low power, on target areas--did not demonstrate a meaningful effect size in DS. A dose-finding study for tPBM in DS, also accounting for age of participants, is recommended.