Cerebral perfusion mediated by thalamo-cortical functional connectivity in non-dominant thalamus affects naming ability in aphasia.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.

Disentangling in-vivo microstructural changes of white and gray matter in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

The microstructural characteristics of white and gray matter in mild cognitive impairment (MCI) and the early-stage of Alzheimer's disease (AD) remain unclear. This study aimed to systematically identify the microstructural damages of MCI/AD in studies using neurite orientation dispersion and density imaging (NODDI), and explore their correlations with cognitive performance. Multiple databases were searched for eligible studies. The 10 eligible NODDI studies were finally included. Patients with MCI/AD showed overall significant reductions in neurite density index (NDI) of specific white matter structures in bilateral hemispheres (left hemisphere: -0.40 [-0.53, -0.27], P < 0.001; right: -0.33 [-0.47, -0.19], P < 0.001), involving the bilateral superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), the left posterior thalamic radiation (PTR), and the left cingulum. White matter regions exhibited significant increased orientation dispersion index (ODI) (left: 0.25 [0.02, 0.48], P < 0.05; right: 0.27 [0.07, 0.46], P < 0.05), including the left cingulum, the right UF, and the bilateral parahippocampal cingulum (PHC), and PTR. Additionally, the ODI of gray matter showed significant reduction in bilateral hippocampi (left: -0.97 [-1.42, -0.51], P < 0.001; right: -0.90 [-1.35, -0.45], P < 0.001). The cognitive performance in MCI/AD was significantly associated with NDI (r = 0.50, P < 0.001). Our findings highlight the microstructural changes in MCI/AD were characterized by decreased fiber orientation dispersion in the hippocampus, and decreased neurite density and increased fiber orientation dispersion in specific white matter tracts, including the cingulum, UF, and PTR. Moreover, the decreased NDI may indicate the declined cognitive level of MCI/AD patients.

Phototherapy for Cognitive Function in Patients With Dementia: A Systematic Review and Meta-Analysis.

Background: Dementia is a major health burden worldwide. As numerous pharmacological trials for dementia have failed, emerging phototherapy studies have evaluated the efficacy of alternative therapies for cognition. Objective: The objective of this study was to evaluate the association between phototherapy and changes in cognitive deficits in patients with dementia. Methods: PubMed, Embase, Web of Science, PsycINFO, CINAHL, and Cochrane Central Register of Controlled Trials were searched from inception to 27 March 2022. Inclusion criteria were controlled clinical trials of phototherapy interventions reporting pre-post changes in global cognitive function and subdomains in patients with dementia. Data were extracted by two independent reviewers and pooled in random-effects models. Subgroup and meta-regression analyses were conducted to investigate the sources of heterogeneity. Results: Our analyses included 13 studies enrolling a total of 608 participants. Phototherapy showed significant associations with improvements of global cognitive function (standardized mean difference [SMD], 0.63; 95% confidence interval [CI], 0.33-0.94; P < 0.001) and subdomains, especially with respect to attention, executive function, and working memory. Near-infrared (NIR) light-emitting diodes (LEDs) photobiomodulation (SMD, 0.91; 95% CI, 0.46-1.36; P < 0.001) and lasers (SMD, 0.99; 95% CI, 0.56-1.43; P < 0.001) showed more significant associations with improved cognitive functions when compared with normal visible light. In addition, the effect sizes of short-term effects (SMD, 0.63; 95% CI, 0.33-0.94; P < 0.001) were larger than effects assessed in long-term follow-up (SMD, 0.49; 95% CI, -0.24-1.21; P = 0.189). Conclusion: In this meta-analysis, phototherapy interventions were associated with cognitive improvement in patients with dementia. NIR LEDs and lasers had advantages over normal visible light. Domain-specific effects were indicated for attention, executive function, and working memory. Short-term improvement after phototherapy was supported, while evidence for long-term benefits was lacking. Stronger evidence for individualized parameters, such as optimal dosing, is needed in the future. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=267596], identifier [CRD42021267596].

Altered Coupling Between Cerebral Blood Flow and Voxel-Mirrored Homotopic Connectivity Affects Stroke-Induced Speech Comprehension Deficits.

The neurophysiological basis of the association between interhemispheric connectivity and speech comprehension processing remains unclear. This prospective study examined regional cerebral blood flow (CBF), homotopic functional connectivity, and neurovascular coupling, and their effects on comprehension performance in post-stroke aphasia. Multimodal imaging data (including data from functional magnetic resonance imaging and arterial spin labeling imaging) of 19 patients with post-stroke aphasia and 22 healthy volunteers were collected. CBF, voxel-mirrored homotopic connectivity (VMHC), CBF-VMHC correlation, and CBF/VMHC ratio maps were calculated. Between-group comparisons were performed to identify neurovascular changes, and correlation analyses were conducted to examine their relationship with the comprehension domain. The correlation between CBF and VMHC of the global gray matter decreased in patients with post-stroke aphasia. The total speech comprehension score was significantly associated with VMHC in the peri-Wernicke area [posterior superior temporal sulcus (pSTS): r = 0.748, p = 0.001; rostroventral area 39: r = 0.641, p = 0.008]. The decreased CBF/VMHC ratio was also mainly associated with the peri-Wernicke temporoparietal areas. Additionally, a negative relationship between the mean CBF/VMHC ratio of the cingulate gyrus subregion and sentence-level comprehension was observed (r = -0.658, p = 0.006). These findings indicate the contribution of peri-Wernicke homotopic functional connectivity to speech comprehension and reveal that abnormal neurovascular coupling of the cingulate gyrus subregion may underly comprehension deficits in patients with post-stroke aphasia.

Comparative Efficacy and Patient-Specific Moderating Factors of Nonsurgical Treatment Strategies for Frozen Shoulder: An Updated Systematic Review and Network Meta-analysis.

BACKGROUND: Frozen shoulder is a common shoulder disorder characterized by pain and restriction. Various nonsurgical treatments have been reported, but there is no consensus about their comparative efficacy and the effects of moderators. PURPOSE: To compare the efficacy of different nonsurgical interventions and identify potential patient-specific moderating factors for frozen shoulder. STUDY DESIGN: Systematic review and network meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception to February 18, 2019. The search was supplemented by manual review of relevant reference lists. Randomized controlled trials of participants with frozen shoulder that compared nonsurgical interventions were selected. Measured outcomes included pain, shoulder function in daily activities, and range of motion. RESULTS: Of 3136 records identified, 92 trials were eligible, evaluating 32 nonsurgical interventions in 5946 patients. Intra-articular injection improved pain (pooled standardized mean difference [95% CI]: steroid injection, 1.68 [1.03-2.34]; capsular distension, 2.68 [1.32-4.05]) and shoulder function (steroid injection, 2.16 [1.52-2.81]; distension, 2.89 [1.71-4.06]) to a greater extent than placebo. Capsular distension and extracorporeal shockwave therapy showed the highest ranking for pain relief and functional improvement, respectively. Laser therapy also showed benefits for pain relief (3.02 [1.84-4.20]) and functional improvement (3.66 [1.65-5.67]). Subgroup analyses by disease stages revealed that steroid injection combined with physical therapy provided more benefits during the freezing phase, whereas joint manipulation provided more benefits in the adhesive phase. Adjunctive therapies, female sex, and diabetes were also identified as moderators of effectiveness. CONCLUSION: Capsular distension is a highly recommended choice for treatment of frozen shoulder, contributing greatly to pain relief and functional improvement; steroid injection is also a prevailing effective intervention. Among new options, extracorporeal shockwave therapy and laser therapy show potential benefits for multiple outcomes. Individualized optimal intervention should be considered, given that treatment effect is moderated by factors including the disease stage, time of assessment, adjunctive therapies, female sex, and diabetes.

Fixel-based evidence of microstructural damage in crossing pathways improves language mapping in Post-stroke aphasia.

BACKGROUND: The complex crossing-fiber characteristics in the dual-stream system have been ignored by traditional diffusion tensor models regarding disconnections in post-stroke aphasia. It is valuable to identify microstructural damage of crossing-fiber pathways and reveal accurate fiber-specific language mapping in patients with aphasia. METHODS: This cross-sectional study collected magnetic resonance imaging data from 29 participants with post-stroke aphasia in the subacute stage and from 33 age- and sex-matched healthy controls. Fixel-based analysis was performed to examine microstructural fiber density (FD) and bundle cross-section alterations of specific fiber populations in crossing-fiber regions. Group comparisons were performed, and relationships with language scores were assessed. RESULTS: The aphasic group exhibited significant fixel-wise FD reductions in the dual-stream tracts, including the left inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus, and superior longitudinal fasciculus (SLF) III (family-wise-error-corrected p < 0.05). Voxel- and fixel-wise comparisons revealed mismatched distributions in regions with crossing-fiber nexuses. Fixel-wise correlation analyses revealed significant associations between comprehension impairment and reduced FD in the temporal and frontal segments of the left IFOF, and also mapped naming ability to the IFOF. Average features along the whole course of dominant tracts assessed with tract-wise analyses attributed word-level comprehension to the IFOF (r = 0.723, p < 0.001) and revealed a trend-level correlation between sentence-level comprehension and FD of the SLF III (r = 0.451, p = 0.021). The mean FD of the uncinate fasciculus (UF) and IFOF correlated with total and picture naming scores, and the IFOF also correlated with responsive naming subdomains (Bonferroni corrected p < 0.05). CONCLUSIONS: FD reductions of dual streams suggest that intra-axonal volume reduction constitutes the microstructural damage of white matter integrity in post-stroke aphasia. Fixel-based analysis provides a complementary method of language mapping that identifies fiber-specific tracts in the left hemisphere language network with greater specificity than voxel-based analysis. It precisely locates the precise segments of the IFOF for comprehension, yields fiber-specific evidence for the debated UF-naming association, and reveals dissociative subdomain associations with distinct tracts.