1 Brain Language Laboratory, Freie Universität Berlin, Germany (A.-T.P.J., M.R.O., A.S., F.P.).
2 Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (A.-T.P.J., C.J.S., V.N.).
3 Department of Psychology, School of Health, Concordia University, Montreal, QC, Canada (C.J.S.).
4 Medizinische Fakultät OWL, Universität Bielefeld, Germany (F.R.D.).
5 Einstein Center for Neurosciences, Berlin, Germany (M.R.O., F.P.).
6 ZeNIS-Center for Neuropsychology and Intensive Language Therapy, Berlin, Germany (B.M.).
7 Cluster of Excellence Matters of Activity. Image Space Material, Humboldt Universität zu Berlin, Germany (F.P.).
8 Berlin School of Mind and Brain, Humboldt Universität zu Berlin, Germany (F.P.).

Background: Intensive language-action therapy treats language deficits and depressive symptoms in chronic poststroke aphasia, yet the underlying neural mechanisms remain underexplored. Long-range temporal correlations (LRTCs) in blood oxygenation level-dependent signals indicate persistence in brain activity patterns and may relate to learning and levels of depression. This observational study investigates blood oxygenation level-dependent LRTC changes alongside therapy-induced language and mood improvements in perisylvian and domain-general brain areas.

Methods: Sixteen patients with chronic poststroke aphasia underwent functional magnetic resonance imaging before and after 2 to 4 weeks of intensive language-action therapy. Therapy took place at Freie Universität Berlin (2014-2020). Language functions and depression were assessed using the Aachen Aphasia Test, the Beck Depression Inventory, and the Montgomery-Åsberg Depression Rating Scale. We implemented a passive reading functional magnetic resonance imaging paradigm and analyzed data using detrended fluctuation analysis to assess LRTC. A 2×2×2 (time, hemisphere, and region of interest) repeated measures ANCOVA (covariates: age, lesion size, time poststroke, and therapy intensity) was conducted in frontoparietal/temporal perisylvian areas across hemispheres before/after therapy. Correlation analyses explored links between changes in behavior and LRTC in focal perisylvian areas and across the whole brain.

Results: Younger patients (relative to the continuous age range of our sample) showed reductions in LRTC across therapy, whereas relatively older patients tended toward increases. We found that changes in LRTC correlated with changes in language performance in right hemisphere perisylvian regions and bilateral domain-general and memory areas (eg, hippocampus, thalamus, supplementary motor area, and putamen). Similarly, changes in depressive symptoms correlated with LRTC changes in right hemisphere perisylvian regions.

Conclusions: LRTC changes across therapy reflect changes in both language performance and depression in chronic poststroke aphasia. Predominantly right perisylvian and domain-general regions seem critical for neuroplasticity in language rehabilitation. In addition, the observed role of right perisylvian regions in mood regulation highlights the interconnection of cognitive recovery and emotional well-being. LRTC may represent a valuable biomarker for tracking therapy-related neuroplasticity.