Conventional transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) could improve arousal in disorders of consciousness (DOC). However, the comparative effectiveness of anodal stimulation of the left DLPFC and the electrophysiological effect of tDCS are yet to be determined. In this randomized sham-controlled design, patients were separated into three groups (left/right anodal tDCS, sham). Data on the clinical assessments and EEG were collected at baseline and after 2 weeks of tDCS. The outcome at 3-month follow-up was evaluated using the Glasgow Outcome Scale-Extended. Results showed that sessions of the left tDCS facilitated the excitability of the prefrontal cortex, whereas only one patient had a positive outcome. Targeting the right DLPFC was less effective, merely leading to activation of the stimulation site, with no effect on the state of arousal. Moreover, sham stimulation had minimal or no effect on any of the outcomes. These results provide evidence for a hemispheric asymmetry of tDCS effects in patients with DOC. Left anodal tDCS might be more effective for modulating cortical excitability compared to tDCS on the right DLPFC. However, future studies with large sample sizes are needed to confirm these findings. This trial is registered with NCT03809936.

In the dual-route language model, the dorsal pathway is known for sound-to-motor mapping, but the role of the ventral stream is controversial. With the goal of enhancing our understanding of language models, this study investigated the diffusion characteristics of candidate tracts in aphasic patients. We evaluated 14 subacute aphasic patients post-stroke and 11 healthy controls with language assessment and diffusion magnetic resonance imaging. Voxel-based lesion-symptom mapping found multiple linguistic associations for the ventral stream, while automated fiber quantification (AFQ) showed, via reduced fractional anisotropy (FA) and axial diffusivity with increased radial diffusivity (all corrected p < 0.05), that the integrity of both the left dorsal and ventral streams was compromised. The average diffusion metrics of each fascicle provided by AFQ also confirmed that voxels with significant FA-language correlations were located in the ventral tracts, including the left inferior fronto-occipital fascicle (IFOF) (comprehension: r = 0.839, p = 0.001; repetition: r = 0.845, p = 0.001; naming: r = 0.813, p = 0.002; aphasia quotient: r = 0.847, p = 0.001) and uncinate fascicle (naming: r = 0.948, p = 0.001). Furthermore, point-wise AFQ revealed that the segment of the left IFOF with the strongest correlations was its narrow stem. The temporal segment of the left inferior longitudinal fascicle was also found to correlate significantly with comprehension (r = 0.663, p = 0.03) and repetition (r = 0.742, p = 0.009). This preliminary study suggests that white matter integrity analysis of the ventral stream may have the potential to reveal aphasic severity and guide individualized rehabilitation. The left IFOF, specifically its narrow stem segment, associates with multiple aspects of language, indicating an important role in semantic processing and multimodal linguistic functions.

Objective To investigate relationships between cognitive domains and white matter changes in different regions in patients with cognitive deficits after traumatic brain injury (TBI). Methods Databases including PubMed, Embase, Web of Science and CENTRAL were searched for studies published before 5 August 2017. Correlation coefficients between cognition and white matter integrity, measured by diffusion metrics, including fractional anisotropy (FA), were pooled from 49 studies including 1405 patients. The influence of demographic factors was assessed by meta-regression analysis. Results Significant pooled FA–executive correlations (p<0.001) were found across various regions, including the corpus callosum (CC) (r=0.42, 95% CI 0.30 to 0.54), superior longitudinal fasciculus (r=0.50, 95% CI 0.41 to 0.59) and internal capsule (IC) (r=0.49, 95% CI 0.37 to 0.61). The fornix (r=0.62, 95% CI 0.45 to 0.78) and cingulum (r=0.57, 95% CI 0.34 to 0.81) particularly correlated with memory (p<0.001). The CC and IC also showed significant relationships with attention and processing speed (p<0.001). Demographic factors had no influence overall, except that studies with a greater proportion of males had stronger correlations between memory and white matter (p<0.05). Conclusions FA is the most sensitive metric for detecting post-TBI cognitive decline across various domains. Representative white matter regions, such as the CC and IC, perform better than whole-brain white matter for reflecting a wide range of cognitive domains, including memory, attention and executive functions. Moreover, the fornix and cingulum particularly reflect memory function. They yield insights into particular imaging indicators that have neuropsychological value.

Background: We hypothesize that the anterior insula is important for maintenance of awareness. Here, we explored the functional connectivity alterations of the anterior insula with changes in the consciousness level or over time in patients with disorders of consciousness (DOC) and determined potential correlation with clinical outcomes. Methods: We examined 20 participants (9 patients with DOC and 11 healthy controls). Each patient underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a standardized Coma Recovery Scale-Revised (CRS-R) assessment on the same day. We categorized the patients according to the prognosis: those who emerged from a minimally conscious state (recovery group, n = 4) and those who remained in the unconscious state (unrecovery group, n = 5). Two rs-fMRI scans were obtained from all patients, and the second scan of patients in the recovery group was obtained after they regained consciousness. We performed seed-based fMRI analysis and selected the left ventral agranular insula (vAI) and dorsal agranular insula (dAI) as the regions of interest. Correlations with CRS-R were determined with the Spearman's correlation coefficient. Results: Compared with healthy controls, the functional connectivity between dAI and gyrus rectus of patients who recovered was significantly increased (p < 0.001, cluster-wise family-wise error rate [FWER] < 0.05). The second rs-fMRI scan of patients who remained with DOC showed a significant decreased functional connectivity between the dAI to contralateral insula, pallidum, bilateral inferior parietal lobule (IPL), precentral gyrus, and middle cingulate cortex (p < 0.001, cluster-wise FWER < 0.05) as well as the functional connectivity between vAI to caudate and cingulum contrast to controls (p < 0.001, cluster-wise FWER < 0.05). Finally, the functional connectivity strength of dAI-temporal pole (Spearman r = 0.491, p < 0.05) and dAI-IPL (Spearman r = 0.579, p < 0.05) were positively correlated with CRS-R scores in all DOC patients. The connectivity of dAI-IPL was also positively correlated with clinical scores in the recovery group (Spearman r = 0.807, p < 0.05). Conclusions: Our findings indicate that the recovery of consciousness is associated with an increased connectivity of the dAI to IPL and temporal pole. This possibly highlights the role of the insula in human consciousness. Moreover, longitudinal variations in dAI-IPL and dAI-temporal pole connectivity may be potential hallmarks in the outcome prediction of DOC patients.