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Basal forebrain nuclei involvement in post-stroke aphasia: Combined effects of cholinergic stimulation and language therapy
Poster Session B, Wednesday, September 30, 4:30 - 6:30 pm, Wangari Maathai
Marcelo L. Berthier1, Guadalupe Davila1, Jose Paredes-Pacheco1, Africa Y. Gomez-Perez1, Natalia Garcia-Casares2, Maria Jose Torres-Prioris1, Diana Lopez-Barroso1; 1Unidad de Neurociencia Cognitiva y Afasia (UNCA), Centro de Investigaciones Médico-Sanitarias, IBIMA-Plataforma Bionand, University of Malaga, Malaga, Spain, 2Arterioesclerosis, Prevencion Vascular, Metabolismo y Enfermedades Neurologicas. Centro de Investigaciones Médico-Sanitarias, IBIMA-Plataforma Bionand, University of Malaga, Malaga, Spain
Background: Although donepezil, an acetylcholinesterase inhibitor, is the most extensively studied agent for post-stroke aphasia (PSA), confirming cholinergic depletion remains challenging, resulting in uncertainty regarding neurochemical diagnosis and drug selection. Identification of damage to the nucleus basalis of Meynert (Ch4), the primary source of acetylcholine projections to the anterior language region, provides a clear rationale for the use of cholinergic agents in PSA. Aims: This study investigated the involvement of the basal forebrain nuclei (BFN) in individuals with chronic PSA and evaluated the therapeutic effects of combining cholinergic augmentation with intensive language training. Methods: Longitudinal voxel-based morphometry (VBM) analyses of gray matter (GM) were conducted in a 10-week open-label pharmacological trial. Following baseline assessment (T1), donepezil (10 mg/day) was administered alone (T2: week 1 to week 8) and subsequently in combination with intensive aphasia therapy (30 hours over two weeks) (T3: week 9 to week 10) in 30 patients with chronic PSA. Participants who improved by at least 5 points on the Aphasia Quotient of the Western Aphasia Battery (WAB) were classified as treatment responders. VBM-GM analyses were performed using SPM12 on serial 3T T1-weighted MRI scans acquired at multiple timepoints (T2–T1, T3–T1, and T3–T2), quantitatively normalized for elapsed time between scans and modulated by GM tissue maps to generate GM change images. An MRI mask of the cholinergic basal forebrain (CBF) was applied. Responders were classified according to CBF status (CBF-lesioned or CBF-spared), and one-sample t-tests and correlations with WAB-R scores were conducted in SPM12 (p < 0.001 voxel-level, p < 0.05 FWE cluster-corrected). Results: At endpoint (T3: week 10), 24 patients were classified as responders, all of whom had left cortico-subcortical lesions involving either the posterior CBF (Ch4p division of the nucleus basalis of Meynert; n = 11) or sparing the entire CBF (n = 13). VBM-GM change images across the T2–T1 interval revealed statistically significant clusters in both responder groups. In the CBF-lesioned group, a significant cluster-level FWE-corrected effect was observed predominantly in the right caudate nucleus, extending into the putamen and pallidum (pFWE-corr at cluster-level = 4.40 × 10⁻³, k = 321 voxels). In the CBF-spared group, a significant cluster was identified mainly in the right putamen and insular cortex (pFWE-corr at cluster-level = 2.10 × 10⁻³, k = 341 voxels). In both groups, VBM-GM changes following donepezil alone did not correlate with language performance (T2–T1), and the initial GM expansion returned to baseline volume (map expansion and renormalization). Notably, only in the CBF-lesioned group did correlation analyses between GM changes during the T3–T1 interval and spontaneous speech WAB scores reveal a significant positive cluster centered in the right central operculum, extending into the right transverse temporal gyrus and posterior insula (pFWE-corr at cluster-level = 2.31 × 10⁻8, k = 1553 voxels). Conclusion: These findings demonstrate two distinct phases of right hemisphere adaptive structural plasticity in chronic aphasic patients in response to combined donepezil and intensive language training, particularly among those with left Ch4p damage.
Topic Areas: Speech-Language Treatment, Language Production