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Close interactions between the brainstem, subcortical structures and cortex play a crucial role in awareness, behavior, cognitive and motor functions regulation. Therefore evaluation of deep brain structures damage may provide a key to outcome prediction and development a new treatment strategy in severe traumatic brain injury (TBI). METHODS We examined 122 patients with severe TBI (GCS<8) and selected 77 with diffuse axonal injury and brain contusion (63 and 14 patients). Brain damage localization was verified by 3T MRI (T1, T2, FLAIR, T2 GRE/SWAN, DWI). We analyzed the damage of Globus Pallidus interna (GPi) and externa (GPe), nucleus caudatus (NC), putamen (Put), Thalamus, Meynert nucleus area and brainstem (Ventral Tegmental Area, Substantia Nigra, Locus Coeruleus, Pedunculopontine Nucleus, Laterodorsal Tegmental Nucleus zones), central tegmental area (CTA). Unconsciousness was evaluated by Dobrokhotova scale and includes coma, vegetative state and akinetic mutism. Coma depth was ranged by GCS and FOUR scale. RESULTS 1. Muscular hypertonia was associated with damage of GPe and cholinergic area of pons, prolonged hypertony – with putamen and substantia nigra damage. 2. Muscular hypotony was associated with thalamus and Meynert nucleus damage. 3. Hyperkinetic syndromes were associated with putamen, GPi, ventral tegmental area, NC damage. 4. Prolonged unconsciousness (more then 1 month) was mole likely associated with concomitant damage to three subcortical structures (paleostriatum, neostriatum or thalamus). 4. Prolonged (≥13 days) and deep (3-4 GCS) coma was associated with damage of dorsolateral part of pons (LCA, PPN and LDT areas), CTA, more often GP and Tha injury. 5. Brain trauma outcome negatively correlated with basal ganglia and midbrain damage. CONCLUSIONS Deep brain structures damage evaluation from the neurotransmitter point of view may provide a key to better pathophysiology understanding, which leads to more accurate outcome prediction in severe TBI.