Cortical surface morphometry changes following combined translingual neural stimulation with the portable neuromodulation stimulator and physical therapy in patients with mild-to-moderate traumatic brain injury: a pilot study

Background Traumatic brain injury (TBI) often causes persistent balance and gait deficits, especially in mild-to-moderate TBI (mmTBI). Physical therapy is standard but often limited as a standalone treatment. Translingual neural stimulation (TLNS) is an emerging neuromodulation approach combining cranial nerve stimulation with targeted exercise to promote neuroplasticity and recovery. Its effects on cortical surface morphometry in mmTBI remain uninvestigated. Methods This secondary analysis used data from a completed clinical trial (NCT02158494). Nine chronic mmTBI patients underwent a two-week intervention combining TLNS (PoNS®) with targeted exercise training; no untreated, physical-therapy-only, or sham group was included. Balance and gait were assessed via the Sensory Organization Test (SOT) and Dynamic Gait Index (DGI) before and after the two-week in-lab phase. High-resolution T1-weighted MRI was acquired at both time points. Cortical thickness (CT), fractal dimensionality (FD), gyrification index (GI), and sulcal depth (SD) were analyzed using CAT12 with non-parametric permutation testing and TFCE correction. Results SOT and DGI scores improved significantly; due to the single-group design, these pre–post changes cannot be attributed to TLNS, physical therapy, or their combination. Widespread pre-post CT increases occurred in bilateral frontal, temporal, parietal, and cingulate regions. FD showed increases (precuneus, insula, and superior frontal gyrus) and decreases (lateral occipital, inferior temporal gyri). GI decreased in the left lingual gyrus; SD showed bidirectional changes. Exploratory correlations linked greater behavioral gains with smaller CT increases in right inferior temporal gyrus and right superior parietal lobule, and smaller FD increases in left precuneus; these were underpowered ( N = 9), uncorrected, and hypothesis-generating only. Morphometric changes in either direction cannot be assumed to reflect beneficial neuroplasticity. Conclusion In this exploratory, single-group pilot study, cortical surface morphometric changes accompanied balance and gait improvements after combined TLNS plus physical therapy in mm TBI. Without a control group, causality cannot be determined. Findings are preliminary and support randomized, sham-controlled trials, ideally with a physical-therapy-only arm.