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Behavioural diagnosis of patients with disorders of consciousness (DOC) is challenging and prone to inaccuracies. Consequently, there have been increased efforts to develop bedside assessment based on EEG and event-related potentials (ERPs) that are more sensitive to the neural factors supporting conscious awareness. However, individual detection of residual consciousness using these techniques is less established. Here, we hypothesize that the cross-state similarity (defined as the similarity between healthy and impaired conscious states) of passive brain responses to auditory stimuli can index the level of awareness in individual DOC patients. To this end, we introduce the global field time-frequency representation-based discriminative similarity analysis (GFTFR-DSA). This method quantifies the average cross-state similarity index between an individual patient and our constructed healthy templates using the GFTFR as an EEG feature. We demonstrate that the proposed GFTFR feature exhibits superior within-group consistency in 34 healthy controls over traditional EEG features such as temporal waveforms. Second, we observed the GFTFR-based similarity index was significantly higher in patients with a minimally conscious state (MCS, 40 patients) than those with unresponsive wakefulness syndrome (UWS, 54 patients), supporting our hypothesis. Finally, applying a linear support vector machine classifier for individual MCS/UWS classification, the model achieved a balanced accuracy and F1 score of 0.77. Overall, our findings indicate that combining discriminative and interpretable markers, along with automatic machine learning algorithms, is effective for the differential diagnosis in patients with DOC. Importantly, this approach can, in principle, be transferred into any ERP of interest to better inform DOC diagnoses.

Objective: General anesthesia (GA) is necessary for surgery, even for patients in a minimally conscious state (MCS). The characteristics of the electroencephalogram (EEG) signatures of the MCS patients under GA are still unclear. Methods: The EEG during GA were recorded from 10 MCS patients undergoing spinal cord stimulation surgery. The power spectrum, phase-amplitude coupling (PAC), the diversity of connectivity, and the functional network were investigated. Long term recovery was assessed by the Coma Recovery Scale-Revised at one year after the surgery, and the characteristics of the patients with good or bad prognosis status were compared. Results: For the four MCS patients with good prognostic recovery, slow oscillation (0.1–1 Hz) and the alpha band (8–12 Hz) in the frontal areas increased during the maintenance of a surgical state of anesthesia (MOSSA), and “peak-max” and “trough-max” patterns emerged in frontal and parietal areas. During MOSSA, the six MCS patients with bad prognosis demonstrated: increased modulation index, reduced diversity of connectivity (from mean±SD of 0.877 ± 0.003 to 0.776 ± 0.003, p < 0.001), reduced function connectivity significantly in theta band (from mean±SD of 1.032 ± 0.043 to 0.589 ± 0.036, p < 0.001, in prefrontal-frontal; and from mean±SD of 0.989 ± 0.043 to 0.684 ± 0.036, p < 0.001, in frontal-parietal) and reduced local and global efficiency of the network in delta band. Conclusions: A bad prognosis in MCS patients is associated with signs of impaired thalamocortical and cortico-cortical connectivity – as indicated by inability to produce inter-frequency coupling and phase synchronization. These indices may have a role in predicting the long-term recovery of MCS patients.

Several studies have investigated possible role of repetitive transcranial magnetic stimulation (rTMS) in patients with disorder of consciousness (DOC). But the details of patients’ brain responses to the rTMS are yet to be disclosed. The aim of the study is to explore the neural electrical responses of DOC patients to rTMS modulation. DOC Patients [14 vegetative state, seven minimally conscious state (MCS)] and healthy subjects were enrolled and received one session of rTMS. The TMS-electroencephalogram was recorded at before and immediately after rTMS stimulation. TMS-evoked potentials as well as TMS-evoked connectivity were proposed to capture the effective connectivity alteration induced by rTMS. Significant changes of TMS-evoked potential were found in the healthy group but not in DOC patients. TMS-evoked connectivity was significantly enhanced by the rTMS in healthy and MCS groups. In addition, the enhancement was positively correlated with patients’ Coma Recovery Scale-Revised scores. Global synchrony of the TMS-evoked connectivity matrix significantly enhanced by rTMS in the control and MCS groups but not in vegetative state patients. Furthermore, after rTMS stimulation, the similarity of TMS-evoked connectivity patterns between pairwise patients was significantly raised in MCS patients. But no significant changes were found in vegetative state patients. TMS-evoked connectivity reveals that rTMS can effectively modulate effective connectivity of MCS patients, but no evidence of changes in vegetative state patients.

NSI‐566 is a stable, primary adherent neural stem cell line derived from a single human fetal spinal cord and expanded epigenetically with no genetic modification. This cell line is being tested in clinical trials in the U.S. for treatment of amyotrophic lateral sclerosis and spinal cord injury. In a single‐site, phase I study, we evaluated the feasibility and safety of NSI‐566 transplantation for the treatment of hemiparesis due to chronic motor stroke and determined the maximum tolerated dose for future trials. Three cohorts (n= 3 per cohort) were transplanted with one‐time intracerebral injections of 1.2 × 107, 2.4 × 107, or 7.2 × 107cells. Immunosuppression therapy with tacrolimus was maintained for 28 days. All subjects had sustained chronic motor strokes, verified by magnetic resonance imaging (MRI), initiated between 5 and 24 months prior to surgery with modified Rankin Scores [MRSs] of 2, 3, or 4 and Fugl‐Meyer Motor Scores of 55 or less. At the 12‐month visit, the mean Fugl‐Meyer Motor Score (FMMS, total score of 100) for the nine participants showed 16 points of improvement (p= .0078), the mean MRS showed 0.8 points of improvement (p= .031), and the mean National Institutes of Health Stroke Scale showed 3.1 points of improvement (p= .020). For six participants who were followed up for 24 months, these mean changes remained stable. The treatment was well tolerated at all doses. Longitudinal MRI studies showed evidence indicating cavity‐filling by new neural tissue formation in all nine patients. Although this was a small, one‐arm study of feasibility, the results are encouraging to warrant further studies. Stem Cells Translational Medicine2019;8:999–1007 Shown are MRI images from three different perspectives of a subject showing the planned coordinates of the human neural stem cell grafts relative to the stroke lesion and a diagram illustrating the three trajectories of the guiding cannula (three straight lines) and the distribution of the human neural stem cell grafts (green balls).

It has been shown that material surface topography greatly affects cell attachment, growth, proliferation, and differentiation. However, the underlying molecular mechanisms for cell–material interactions are still not understood well. Here, two kinds of butterfly wings with different surface architectures were employed for addressing such an issue. Papilio ulysses telegonus(P.u.t.) butterfly wing surface is composed of micro/nanoconcaves, whereas Morpho menelaus(M.m.) butterfly wings are decorated with grooves. RSC96 cells grown on M.m. wings showed a regular sorting pattern along with the grooves. On the contrary, the cells seeded on P.u.t. wings exhibited random arrangement. Transcriptome sequencing and bioinformatics analysis revealed that huntingtin (Htt)-regulated lysosome activity is a potential key factor for determining cell growth behavior on M.m. butterfly wings. Gene silence further confirmed this notion. In vivoexperiments showed that the silicone tubes fabricated with M.m. wings markedly facilitate rat sciatic nerve regeneration after injury. Lysosome activity and Htt expression were greatly increased in the M.m. wing-fabricated graft-bridged nerves. Collectively, our data provide a theoretical basis for employing butterfly wings to construct biomimetic nerve grafts and establish Htt lysosome as a crucial regulator for cell–material interactions.

Repetitive transcranial magnetic stimulation (rTMS) has been applied for the treatment of patients with disorders of consciousness (DOC). Timely and accurate assessments of its modulation effects are very useful. This study evaluated rTMS modulation effects on electroencephalography (EEG) oscillation in patients with chronic DOC. Eighteen patients with a diagnosis of DOC lasting more than 3 months were recruited. All patients received one session of 10-Hz rTMS at the left dorsolateral prefrontal cortex and then 12 of them received consecutive rTMS treatment everyday for 20 consecutive days. Resting-state EEGs were recorded before the experiment (T0) after one session of rTMS (T1) and after the entire treatment (T2). The JFK Coma Recovery Scale-Revised scale scores were also recorded at the time points. Our data showed that application of 10-Hz rTMS to the left dorsolateral prefrontal cortex decreased low-frequency band power and increased high-frequency band power in DOC patients, especially in minimal conscious state patients. Considering the correlation of the EEG spectrum with the consciousness level of patients with DOC, quantitative EEG might be useful for assessment of the effect of rTMS in DOC patients.