Neurotransmitters’ white matter mapping unveils the neurochemical fingerprints of stroke

Abstract

Distinctive patterns of brain neurotransmission frame determinant circuits for behavior. Understanding the relationship between their damage and the cognitive impairment provoked by brain lesions could provide important insights into the pathophysiology and therapeutics of highly disabling disorders, like stroke. Yet, the challenges of neurotransmitter circuits mapping in vivo have hampered this investigation. Here, we developed a novel MRI white matter atlas of neurotransmitter circuits and created a method to chart how stroke damages neurotransmitter systems, which innovatively distinguishes pre and postsynaptic disruption. We trained and tested our model in two large stroke patient samples and showed the existence of eight clusters with different neurochemical patterns. The associations with patients’ cognitive profiles were scarce, reinforcing that a cognitive network might be affected at different neurochemical levels. These findings unravel the relationship between neurotransmitters and behavior, depict the patterns of stroke neurochemical diaschisis, and open a new window for tailored neurotransmitter modulation.