Background and Purpose: Optimizing speech and language therapy (SLT) regimens for maximal aphasia recovery is a clinical research priority. We examined associations between SLT intensity (hours/week), dosage (total hours), frequency (days/week), duration (weeks), delivery (face to face, computer supported, individual tailoring, and home practice), content, and language outcomes for people with aphasia. Methods: Databases including MEDLINE and Embase were searched (inception to September 2015). Published, unpublished, and emerging trials including SLT and ≥10 individual participant data on aphasia, language outcomes, and time post-onset were selected. Patient-level data on stroke, language, SLT, and trial risk of bias were independently extracted. Outcome measurement scores were standardized. A statistical inferencing, one-stage, random effects, network meta-analysis approach filtered individual participant data into an optimal model examining SLT regimen for overall language, auditory comprehension, naming, and functional communication pre-post intervention gains, adjusting for a priori–defined covariates (age, sex, time poststroke, and baseline aphasia severity), reporting estimates of mean change scores (95% CI). Results: Data from 959 individual participant data (25 trials) were included. Greatest gains in overall language and comprehension were associated with >20 to 50 hours SLT dosage (18.37 [10.58–26.16] Western Aphasia Battery–Aphasia Quotient; 5.23 [1.51–8.95] Aachen Aphasia Test–Token Test). Greatest clinical overall language, functional communication, and comprehension gains were associated with 2 to 4 and 9+ SLT hours/week. Greatest clinical gains were associated with frequent SLT for overall language, functional communication (3–5+ days/week), and comprehension (4–5 days/week). Evidence of comprehension gains was absent for SLT ≤20 hours, <3 hours/week, and ≤3 days/week. Mixed receptive-expressive therapy, functionally tailored, with prescribed home practice was associated with the greatest overall gains. Relative variance was <30%. Risk of trial bias was low to moderate; low for meta-biases. Conclusions: Greatest language recovery was associated with frequent, functionally tailored, receptive-expressive SLT, with prescribed home practice at a greater intensity and duration than reports of usual clinical services internationally. These exploratory findings suggest critical therapeutic ranges, informing hypothesis-testing trials and tailoring of clinical services. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42018110947.

Background: To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients. Results: Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas. Conclusion: The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.