Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis

ObjectiveThe aim of this study is to evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with disorders of consciousness (DoC) and compare differences in efficacy between different stimulation modalities.MethodsWe searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for all studies published in English from inception to April 2023. Literature screening and quality assessment were performed independently by two investigators. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to evaluate the therapeutic effects of NIBS. The Cochrane Q test and I2 statistic were used to evaluate heterogeneity between studies. Subgroup analysis was performed to identify the source of heterogeneity, and differences in efficacy between different stimulation modalities were compared by Bayesian analysis.ResultsA total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when compared to sham stimulation (WMD: 0.81; 95% CI: 0.46, 1.17; I2 = 78.2%, p = 0.000). When divided into subgroups according to stimulation modalities, the heterogeneity of each subgroup was significantly lower than before (I2: 0.00–30.4%, p >0.05); different stimulation modalities may be the main source of such heterogeneity. Bayesian analysis, based on different stimulation modalities, indicated that a patient’s state of consciousness improved most significantly after repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Diagnosis-based subgroup analysis showed that NIBS significantly improved the state of consciousness in patients with a minimal consciousness state (WMD: 1.11; 95% CI: 0.37, 1.86) but not in patients with unresponsive wakefulness syndrome or a vegetative state (WMD: 0.31; 95% CI: −0.09, 0.71). Subgroup analysis based on observation time showed that single treatment did not improve the state of consciousness in DoC patients (WMD: 0.28; 95% CI: −0.27, 0.82) while multiple treatments could (WMD: 1.05; 95% CI: 0.49, 1.61). Furthermore, NIBS had long-term effects on DoC patients (WMD: 0.79; 95% CI: 0.08–1.49).ConclusionAvailable evidence suggests that the use of NIBS on patients with DoC is more effective than sham stimulation, and that rTMS of the left DLPFC may be the most prominent stimulation modality

Variation in brain connectivity during motor imagery and motor execution in stroke patients based on electroencephalography

ObjectiveThe objective of this study was to analyze the changes in connectivity between motor imagery (MI) and motor execution (ME) in the premotor area (PMA) and primary motor cortex (MA) of the brain, aiming to explore suitable forms of treatment and potential therapeutic targets.MethodsTwenty-three inpatients with stroke were selected, and 21 right-handed healthy individuals were recruited. EEG signal during hand MI and ME (synergy and isolated movements) was recorded. Correlations between functional brain areas during MI and ME were compared.ResultsPMA and MA were significantly and positively correlated during hand MI in all participants. The power spectral density (PSD) values of PMA EEG signals were greater than those of MA during MI and ME in both groups. The functional connectivity correlation was higher in the stroke group than in healthy people during MI, especially during left-handed MI. During ME, functional connectivity correlation in the brain was more enhanced during synergy movements than during isolated movements. The regions with abnormal functional connectivity were in the 18th lead of the left PMA area.ConclusionLeft-handed MI may be crucial in MI therapy, and the 18th lead may serve as a target for non-invasive neuromodulation to promote further recovery of limb function in patients with stroke. This may provide support for the EEG theory of neuromodulation therapy for hemiplegic patients

Deep learning for the rapid automatic segmentation of forearm muscle boundaries from ultrasound datasets

Ultrasound (US) is widely used in the clinical diagnosis and treatment of musculoskeletal diseases. However, the low efficiency and non-uniformity of artificial recognition hinder the application and popularization of US for this purpose. Herein, we developed an automatic muscle boundary segmentation tool for US image recognition and tested its accuracy and clinical applicability. Our dataset was constructed from a total of 465 US images of the flexor digitorum superficialis (FDS) from 19 participants (10 men and 9 women, age 27.4 ± 6.3 years). We used the U-net model for US image segmentation. The U-net output often includes several disconnected regions. Anatomically, the target muscle usually only has one connected region. Based on this principle, we designed an algorithm written in C++ to eliminate redundantly connected regions of outputs. The muscle boundary images generated by the tool were compared with those obtained by professionals and junior physicians to analyze their accuracy and clinical applicability. The dataset was divided into five groups for experimentation, and the average Dice coefficient, recall, and accuracy, as well as the intersection over union (IoU) of the prediction set in each group were all about 90%. Furthermore, we propose a new standard to judge the segmentation results. Under this standard, 99% of the total 150 predicted images by U-net are excellent, which is very close to the segmentation result obtained by professional doctors. In this study, we developed an automatic muscle segmentation tool for US-guided muscle injections. The accuracy of the recognition of the muscle boundary was similar to that of manual labeling by a specialist sonographer, providing a reliable auxiliary tool for clinicians to shorten the US learning cycle, reduce the clinical workload, and improve injection safety

Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study

ObjectiveThe purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function.MethodsThirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations.ResultCompared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = −2.175, p = 0.034), gamma (t = −2.332, p = 0.023), and local efficiency (t = −2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = −3.581, p = 0.0007), and the network efficiency values (t = −2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores.ConclusionOur study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP

Effects of Tactile Sensitivity on Structural Variability of Digit Forces during Stable Precision Grip

This study investigated the effects of fingertip tactile sensitivity on the structural variability of thumb and index finger forces during stable precision grip. Thirty right-handed healthy subjects participated in the experiment. Transient perturbation of tactile afferents was achieved by wrapping up the distal pads of the thumb or index finger with transparent polyethylene films. The time-dependent structure of each digit force and the variability of interdigit force correlation were examined by detrended fluctuation analysis (DFA) and detrended cross-correlation analysis (DCCA), respectively. Results showed that the tactile sensitivity affected αDFA of the vertical shear force Fx (F3,239 = 6.814, p<0.001) and αDCCA of Fx (χ2 = 16.440, p<0.001). No significant difference was observed in αDFA or αDCCA of the normal forces produced by the thumb or index finger. These results suggested that with blurred tactile sensory inputs the central nervous system might decrease the vertical shear force flexibility and increase the interdigit shear force coupling in order to guarantee a stable grip control of an object against gravity. This study shed light on the feedback and feed-forward strategies involved in digit force control and the role of SA-II afferent fibers in regulation of vertical shear force variability for precision grip

Analysis of center of mass acceleration and muscle activation in hemiplegic paralysis during quiet standing.

Hemiplegic paralysis after stroke may augment postural instability and decrease the balance control ability for standing. The center of mass acceleration (COMacc) is considered to be an effective indicator of postural stability for standing balance control. However, it is less studied how the COMacc could be affected by the muscle activities on lower-limbs in post-stroke hemiplegic patients. This study aimed to examine the effects of hemiplegic paralysis in post-stroke individuals on the amplitude and structural variabilities of COMacc and surface electromyography (sEMG) signals during quiet standing. Eleven post-stroke hemiplegic patients and the same number of gender- and age-matched healthy volunteers participated in the experiment. The sEMG signals of tibialis anterior (TA) and lateral gastrocnemius (LG) muscles of the both limbs, and the COMacc in the anterior-posterior direction with and without visual feedback (VF vs. NVF) were recorded simultaneously during quiet standing. The sEMG and COMacc were analyzed using root mean square (RMS) or standard deviation (SD), and a modified detrended fluctuation analysis based on empirical mode decomposition (EMD-DFA). Results showed that the SD and the scale exponent α of EMD-DFA of the COMacc from the patients were significantly higher than the values from the controls under both VF (p < 0.01) and NVF (p < 0.001) conditions. The RMSs of TA and LG on the non-paretic limbs were significantly higher than those on paretic limbs (p < 0.05) for both the patients and controls (p < 0.05). The TA of both the paretic and non-paretic limbs of the patients showed augmented α values than the TA of the controls (p < 0.05). The α of the TA and LG of non-paretic limbs, and the α of COMacc were significantly increased after removing visual feedback in patients (p < 0.05). These results suggested an increased amplitude variability but decreased structural variability of COMacc, associated with asymmetric muscle contraction between the paretic and the non-paretic limbs in hemiplegic paralysis, revealing a deficiency in integration of sensorimotor information and a loss of flexibility of postural control due to stroke

Detection of hypochlorous acid fluctuation via a selective fluorescent probe in acute lung injury cells and mouse models

Acute lung injury (ALI) is a diffuse inflammatory pulmonary damage caused by excessive ROS that break the coordination of normal physiological structures and functions. Hypochlorous acid (HOCl), one kind of ROS, is a hopeful biological marker for inflammation-related diseases. Therefore, the excessive generation of HOCl might be a significant reason for oxidative injury in ALI. Herein, we developed a fluorescent probe, namely BCy-HOCl, for quantitatively monitoring and visualizing HOCl in living cells and in vivo. The probe BCy-HOCl displayed a significant fluorescence signal enhancement towards HOCl with excellent selectivity and sensitivity. The variation of HOCl in the ALI cell model and ALI mouse model was evaluated with BCy-HOCl to clarify the relationship between ALI and HOCl. Our results verified that the HOCl levels conspicuously increased with the severity of the ALI. Thus, HOCl is likely to play a crucial part in the process of ALI, which will probably provide a new strategy for its treatment