Objective: The efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30‐Hz low‐frequency stimulation designed to overdrive neuronal activity by dual pallido‐thalamic targeting, using the Coma Recovery Scale Revised (CRS‐R) to assess conscious behavior.Methods: We conducted a prospective, single center, observational 11‐month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5‐month ON and OFF periods; and unblinded, 5‐month stimulation ON. Five adult patients were included: one unresponsive‐wakefulness‐syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS‐R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON – baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random‐effect models.Results: The two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS‐R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders.Interpretation: Our findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo‐cortico‐basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.

Despite a better understanding of brain language organization into large-scale cortical networks, the underlying white matter (WM) connectivity is still not mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and language functional magnetic resonance imaging (fMRI) in twenty healthy subjects to gain new insights into the macroscopic structural connectivity of language. Eight putative WM fascicles for language were probed using a deterministic DTI-FT technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF), uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional anisotropy) and precise cortical terminations were derived for each WM fascicle within both hemispheres. Connections between these WM fascicles and fMRI activations were studied to determine which WM fascicles are related to language. WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal segment of SLF and UF, and rightward for the frontoparietal segment of the SLF. The lateralization of the AF, IFOF and MdLF extended to differences in patterns of anatomical connections, which may relate to specific hemispheric abilities. The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI activations, suggesting that the lateralization of the AF is a structural substrate of hemispheric language dominance. We found consistent connections between fMRI activations and terminations of the eight WM fascicles, providing a detailed description of the language connectome. WM fascicle terminations were also observed beyond fMRI-confirmed language areas and reached numerous cortical areas involved in different functional brain networks. These findings suggest that the reported WM fascicles are not exclusively involved in language and might be related to other cognitive functions such as visual recognition, spatial attention, executive functions, memory, and processing of emotional and behavioral aspects.