Neurotransmitter-Informed Connectome Approach to Language Impairment After Stroke.
L’essentiel
Variability in poststroke language outcomes remains insufficiently explained by established clinical system neuroscience concepts. This study examined whether damage to neurotransmitter-informed structural networks is associated with poststroke language impairment. Two openly available cohorts of patients with left-hemispheric stroke were analyzed: the Washington Stroke Cohort (St. Louis), including patients after a first symptomatic stroke (acute phase), and the Aphasia Recovery Cohort (South Carolina), focusing on chronic recovery. Language performance was assessed cross-sectionally using either a comprehensive language battery (Washington Stroke Cohort; 1-2 weeks poststroke) or the Western Aphasia Battery-Revised (Aphasia Recovery Cohort; chronic stage). Individual stroke lesion masks were embedded into normative connectomes weighted by positron-emission tomography-derived density maps of 16 neurotransmitter receptors/transporters. Partial least squares regression and adjusted linear regressions (age, sex, lesion volume, and time poststroke) identified predictors of language functioning. Two hundred seventy patients were included. Washington Stroke Cohort (n=44): mean age, 54.2±12.3 years; 45.5% female; median, 12 days poststroke (interquartile range, 10-14). Aphasia Recovery Cohort (n=226): mean age, 57.8±11.2 years; 38.4% female; and median, 721 days poststroke (interquartile range, 403-1765). Across both cohorts, partial least squares analyses converged on a neurochemical profile in which damage to networks related to serotonergic (5-HT1a and 5-HT2a) and dopaminergic (D1) receptor distributions showed the strongest associations with poorer language performance. Damage to 5-HT1a and D1 networks remained significant in fully adjusted models, improving fit over covariate-only models (all PFDR<0.001; Washington Stroke Cohort: ∆AIC5-HT1a=1.77 and ∆AICD1=0.96; Aphasia Recovery Cohort: ∆AIC5-HT1a=25.29 and ∆AICD1=19.96). The disruption of large-scale serotonergic (5-HT1a) and dopaminergic (D1) networks is associated with language impairment in acute to subacute and chronic stroke. Neurotransmitter-related network damage, based on normative positron-emission tomography-derived maps serving as a structural proxy of neurotransmitter systems, explained additional variability beyond clinical variables and lesion burden, providing a neurochemically informed network framework for understanding variability in poststroke aphasia. However, given the indirect nature of the measures, implications for clinical translation and targeted rehabilitation strategies remain preliminary.
Synthèse détaillée
Résumé original
Variability in poststroke language outcomes remains insufficiently explained by established clinical system neuroscience concepts. This study examined whether damage to neurotransmitter-informed structural networks is associated with poststroke language impairment. Two openly available cohorts of patients with left-hemispheric stroke were analyzed: the Washington Stroke Cohort (St. Louis), including patients after a first symptomatic stroke (acute phase), and the Aphasia Recovery Cohort (South Carolina), focusing on chronic recovery. Language performance was assessed cross-sectionally using either a comprehensive language battery (Washington Stroke Cohort; 1-2 weeks poststroke) or the Western Aphasia Battery-Revised (Aphasia Recovery Cohort; chronic stage). Individual stroke lesion masks were embedded into normative connectomes weighted by positron-emission tomography-derived density maps of 16 neurotransmitter receptors/transporters. Partial least squares regression and adjusted linear regressions (age, sex, lesion volume, and time poststroke) identified predictors of language functioning. Two hundred seventy patients were included. Washington Stroke Cohort (n=44): mean age, 54.2±12.3 years; 45.5% female; median, 12 days poststroke (interquartile range, 10-14). Aphasia Recovery Cohort (n=226): mean age, 57.8±11.2 years; 38.4% female; and median, 721 days poststroke (interquartile range, 403-1765). Across both cohorts, partial least squares analyses converged on a neurochemical profile in which damage to networks related to serotonergic (5-HT1a and 5-HT2a) and dopaminergic (D1) receptor distributions showed the strongest associations with poorer language performance. Damage to 5-HT1a and D1 networks remained significant in fully adjusted models, improving fit over covariate-only models (all PFDR<0.001; Washington Stroke Cohort: ∆AIC5-HT1a=1.77 and ∆AICD1=0.96; Aphasia Recovery Cohort: ∆AIC5-HT1a=25.29 and ∆AICD1=19.96). The disruption of large-scale serotonergic (5-HT1a) and dopaminergic (D1) networks is associated with language impairment in acute to subacute and chronic stroke. Neurotransmitter-related network damage, based on normative positron-emission tomography-derived maps serving as a structural proxy of neurotransmitter systems, explained additional variability beyond clinical variables and lesion burden, providing a neurochemically informed network framework for understanding variability in poststroke aphasia. However, given the indirect nature of the measures, implications for clinical translation and targeted rehabilitation strategies remain preliminary.