A Neurochemical Blueprint of Language and Aphasia

A new #preprint from our international collaboration maps the neurochemical architecture of the human language network and shows how different neurotransmitter systems are disrupted in post-stroke aphasia.

By combining large-scale fMRI, PET-derived neurotransmitter maps, and structural connectomics, we demonstrate that language circuits are organised according to distinct neurochemical principles: cortico-cortical pathways are predominantly serotonergic and glutamatergic, while thalamo-cortical projections show strong cholinergic involvement.

Importantly, the study reveals that aphasia is not associated with a single uniform pattern of brain damage. Instead, different lesion locations produce distinct “neurochemical fingerprints”. Lobar lesions were linked to predominantly postsynaptic serotonergic disruption, whereas subcortical aphasia showed stronger presynaptic cholinergic and serotonergic injury profiles.

The work also provides an important translational proof-of-concept: in a post-hoc analysis of pharmacological aphasia trials, patients were more likely to improve when the administered drug matched the dominant disrupted neurotransmitter system identified from their lesion profile. These findings open the possibility of moving toward biologically informed, personalised treatment strategies for aphasia recovery after stroke.

Beyond aphasia, the study introduces a broader framework for understanding cognition through neurotransmitter-weighted brain networks, bridging systems neuroscience, connectomics, and clinical neuropharmacology.

Read the preprint here: https://doi.org/10.64898/2026.05.14.725241

Please cite as: Neurotransmitter circuits of the human language network and their disruption in post-stroke aphasia. Pedro Nascimento Alves, Isabel Pavao Martins, Chris Rorden, Marcelo L Berthier, Guadalupe Davila, Alexander Leff, Michel Thiebaut de Schotten, Stephanie J Forkel. bioRxiv 2026.05.14.725241; doi: https://doi.org/10.64898/2026.05.14.725241