Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect ofl-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects ofl-dopa. Specifically,l-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Althoughl-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

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 Published, unpublished, and emerging trials including SLT and ≥10 individual participant data on aphasia, language outcomes, and time post-onset were selected.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.

The impact of basal ganglia dysfunction on semantic processing was investigated by comparing the performance of individuals with nonthalamic subcortical (NS) vascular lesions, Parkinson's disease (PD), cortical lesions, and matched controls on a semantic priming task. Unequibiased lexical ambiguity primes were used in auditory prime-target pairs comprising 4 critical conditions; dominant related (e.g.,bank–money), subordinate related (e.g.,bank–river), dominant unrelated (e.g.,foot–money) and subordinate unrelated (e.g.,bat–river). Participants made speeded lexical decisions (word/nonword) on targets using a go–no-go response. When a short prime–target interstimulus interval (ISI) of 200 ms was employed, all groups demonstrated priming for dominant and subordinate conditions, indicating nonselective meaning facilitation and intact automatic lexical processing. Differences emerged at the long ISI (1250 ms), where control and cortical lesion participants evidenced selective facilitation of the dominant meaning, whereas NS and PD groups demonstrated a protracted period of nonselective meaning facilitation. This finding suggests a circumscribed deficit in the selective attentional engagement of the semantic network on the basis of meaning frequency, possibly implicating a disturbance of frontal–subcortical systems influencing inhibitory semantic mechanisms. (JINS, 2003,9, 1041–1052.)