Supratentorial Brain Lesions in Unconscious Patients Map to a Common Human Brain Circuit

Impairment of consciousness is frequent in patients with supratentorial brain injury, but underlying mechanisms are poorly understood. Large-scale network dysfunction has been suggested as a unifying concept for the diverse focal infra- and supratentorial brain lesions associated with unconsciousness. Functional imaging studies have revealed that lesions in different locations that cause the same symptom can be linked to common networks using lesion network mapping (LNM).

To identify a commonly injured network for impaired consciousness, LNM was used in a prospective, bi-center observational cohort of 115 humans suffering from focal brain injury due to supratentorial intracerebral hemorrhage (ICH).

Contrasting patients with preserved (n = 45) and impaired consciousness (n = 70), we identified a common network of brain regions more likely to be connected to focal brain lesions associated with impaired consciousness. Lesions in unconscious patients were more likely connected to a network including fronto-insulo-limbic association cortex, subcortical arousal and neuromodulatory nodes, and the ventral striato-pallidal circuitry. Data suggested preferential connectivity to a combination of arousal circuitry and association cortices.

Patients with impaired consciousness shared a common pattern of distributed network involvement that we infer to be mechanistically relevant to the regulation of consciousness that may serve as promising targets of neuromodulatory therapies. ANN NEUROL 2026;100:206-221.