Prolonged intermittent theta burst stimulation for post-stroke aphasia: protocol of a randomized, double-blinded, sham-controlled trial.

Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39 g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR2300074533.

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

[This corrects the article DOI: 10.3389/fnins.2023.1219043.].

Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: a study protocol for a randomized controlled trial.

Background: Upper limb motor recovery is one of the important goals of stroke rehabilitation. Intermittent theta burst stimulation (iTBS), a new type of repetitive transcranial magnetic stimulation (rTMS), is considered a potential therapy. However, there is still no consensus on the efficacy of iTBS for upper limb motor dysfunction after stroke. Stimulus dose may be an important factor affecting the efficacy of iTBS. Therefore, we aim to investigate and compare the effects and neural mechanisms of three doses of iTBS on upper limb motor recovery in stroke patients, and our hypothesis is that the higher the dose of iTBS, the greater the improvement in upper limb motor function. Methods: This prospective, randomized, controlled trial will recruit 56 stroke patients with upper limb motor dysfunction. All participants will be randomized in a 1:1:1:1 ratio to receive 21 sessions of 600 pulses active iTBS, 1,200 pulses active iTBS, 1,800 pulses active iTBS, or 1,800 pulses sham iTBS in addition to conventional rehabilitation training. The primary outcome is the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score from baseline to end of intervention, and the secondary outcomes are the Wolf Motor Function Test (WMFT), Grip Strength (GS), Modified Barthel Index (MBI), and Stroke Impact Scale (SIS). The FMA-UE, MBI, and SIS are assessed pre-treatment, post-treatment, and at the 3-weeks follow-up. The WMFT, GS, and resting-state functional magnetic resonance imaging (rs-fMRI) data will be obtained pre- and post-treatment. Discussion: The iTBS intervention in this study protocol is expected to be a potential method to promote upper limb motor recovery after stroke, and the results may provide supportive evidence for the optimal dose of iTBS intervention.

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

Objective: The 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. Methods: We 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. Results: A 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). Conclusion: Available 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.

Corrigendum: Functional networks in prolonged disorders of consciousness.

[This corrects the article DOI: 10.3389/fnins.2023.1113695.].

Functional networks in prolonged disorders of consciousness.

Prolonged disorders of consciousness (DoC) are characterized by extended disruptions of brain activities that sustain wakefulness and awareness and are caused by various etiologies. During the past decades, neuroimaging has been a practical method of investigation in basic and clinical research to identify how brain properties interact in different levels of consciousness. Resting-state functional connectivity within and between canonical cortical networks correlates with consciousness by a calculation of the associated temporal blood oxygen level-dependent (BOLD) signal process during functional MRI (fMRI) and reveals the brain function of patients with prolonged DoC. There are certain brain networks including the default mode, dorsal attention, executive control, salience, auditory, visual, and sensorimotor networks that have been reported to be altered in low-level states of consciousness under either pathological or physiological states. Analysis of brain network connections based on functional imaging contributes to more accurate judgments of consciousness level and prognosis at the brain level. In this review, neurobehavioral evaluation of prolonged DoC and the functional connectivity within brain networks based on resting-state fMRI were reviewed to provide reference values for clinical diagnosis and prognostic evaluation.

Cytoprotective effects of spleen-invigorating pill against 5-fluorouracil injury to mouse bone marrow stromal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Spleen-invigorating pills (SIP) are composed of Codonopsis, fried Atractylodes, tangerine peel, Fructus aurantii immaturus (fried), fried hawthorn, and colored malt. SIP strengthens the spleen and increases appetite and is often used as a chemotherapy adjuvant. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for SIP on mouse bone marrow stromal cells (OP9) injured by 5-fluorouracil (5-FU). MATERIALS AND METHODS: The effects of SIP on OP9 cells injured by 5-FU were evaluated, and high-performance liquid chromatography (HPLC) was used as a quality control method. The experiments were divided into a control group, a model group, an epidermal growth factor (EGF) treatment group, and an SIP treatment group. The cell survival rate, apoptotic cell morphology, cell apoptosis rate, and the contents of caspase 3 were evaluated to determine the protective effects of SIP in OP9 cells injured by 5-FU. Network pharmacology was used to predict the mechanism through which SIP mediates anti-chemotherapy damage. The nitric oxide (NO) and nitric oxide synthase (iNOS) levels and the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) and p62 protein were detected to explore the mechanism through which SIP mediates anti-chemotherapy damage through the regulation of oxidative stress. RESULTS: Cell counting kit-8 (CCK8) detection showed that 5-FU reduced OP9 cell survival, and SIP blocked the inhibition of OP9 cell growth induced by 5-FU. When OP9 cells were treated with both SIP (10 g L-1) and 5-FU (2.5 × 10-2 g L-1) for 24 h, compared with the model group, the early apoptosis rates significantly decreased, and the activity of caspase 3 was significantly reduced. The results of network pharmacology and Western blot showed that compared with the model group, in the SIP group, the NO levels decreased, iNOS release decreased, and the expression of Nrf2 and p62 proteins increased. CONCLUSION: The protective effects of SIP on OP9 cells injured by 5-FU were significant. SIP may play a cytoprotective role by mediating changes in oxidative stress-related proteins. The specific mechanism of action through which SIP mediates these effects remains to be further studied.

Differences in cognitive profiles between traumatic brain injury and stroke: A comparison of the Montreal Cognitive Assessment and Mini-Mental State Examination.

PURPOSE: To investigate the profiles of cognitive impairment through Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) in patients with chronic traumatic brain injury (TBI) or stroke and to evaluate the sensitivity of the two scales in patients with TBI. METHODS: In this cohort study, a total of 230 patients were evaluated, including TBI group (n = 103) and stroke group (n = 127). The cognitive functions of two groups were evaluated by designated specialists using MoCA (Beijing version) and MMSE (Chinese version). RESULTS: Comparedwith the patientswith stroke, the patientswith TBI received significantly lower score in orientation subtest and recall subtest in both tests.MoCA abnormal rates in the TBI group and stroke group were 94.17% and 86.61% respectively,whileMMSE abnormal rateswere 69.90% and 57.48%, respectively. In the TBI group, 87.10% patientswith normalMMSE score had abnormalMoCA score and in the stroke group, about 70.37% patients with normal MMSE score had abnormal MoCA score. The diagnostic consistency of two scales in the TBI group and the stroke group were 72% and 69%, respectively. CONCLUSION: In our rehabilitation center, patients with TBI may have more extensive and severe cognitive impairments than patients with stroke, prominently in orientation and recall domain. In screening post- TBI cognitive impairment, MoCA tends to be more sensitive than MMSE.

Differences in Cognitive Function of Rats with Traumatic Brain Injuries Following Hyperbaric Oxygen Therapy.

BACKGROUND Hyperbaric oxygen (HBO) is a historical therapeutic option in the treatment of various types of brain damage. At present, clinical treatment of hypoxic-ischemic injury is giving priority to cognitive training. The effects of HBO on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model. MATERIAL AND METHODS Seventy male SD rats were randomly divided into control (n=10) and intervention (n=60) groups. All rats underwent baseline water maze testing 1 day before modeling, and were retested 8 weeks after modeling. The percentage of residence time during escape latency in the target quadrant and the total time were recorded. Data were analyzed by SPSS 16.0 software. P<0.05 was considered statistically significant. RESULTS After 8 weeks, no statistical difference (P>0.05) existed in spatial learning ability in the 3-day and 5-day groups when compared with baseline. The other groups were statistically different by auto-comparison (P<0.05). No statistical difference (P>0.05) in spatial memory existed in the 5-day and 1-week groups when compared with baseline, while a significant difference was noted in the other groups by self-comparison (P<0.05). No statistical difference (P>0.05) was noted in the level of expression of growth-associated protein-43 (GAP-43) and synaptophysin (Syn) in the 1-day group compared with the control group. The remaining groups and the control group were statistically different (P<0.05), while the level of expression of GAP-43 and Syn in the 5-day, 1-week, and 2-week groups was significantly different compared with that in the control group (P<0.01). CONCLUSIONS If HBO therapy was provided 5-7 days after craniocerebral trauma, there was apparent improvement in cognitive function and neuroplasticity.

Assessing consciousness with auditory event-related potential during coma recovery: a case study.

To observe changes in mismatch negativity (MMN) and P300 in a patient transitioning from a vegetative state (VS) to a minimally conscious state (MCS). One patient with intracerebral hemorrhage and an 8-month disease course was evaluated as being in the VS using the Coma Recovery Scale-Revised. Two weeks after the patient was admitted to the hospital, another evaluation was performed, and the patient was determined to be in an MCS. Using the Oddball paradigm, pure tone and name stimuli were presented to the patient to study event-related potentials (ERPs). A 15-week clinical follow-up was carried out, and four ERP examinations were performed at 2 days and 2, 6, and 15 weeks after admission. One healthy individual was assessed as a control participant. MMN and P300 were elicited in all four ERP examinations. MMN and P300 may occur earlier than believed in patients in persistent VS and MCS; their predictive values for prognosis need to be further confirmed by follow-up studies on a large clinical sample.

The effect and mechanism of growth hormone replacement on cognitive function in rats with traumatic brain injury.

OBJECTIVE: The effects of growth hormone on cognitive dysfunction were observed in a controlled cortical impact (CCI) rat model and the underlying mechanism was explored. METHOD: Three-month-old male SD rats were randomly divided into sham (n = 10), control (n = 10), and CCI groups (n = 40) The parameters were set as follows: striking speed, 3.5 m/s; impact depth, 1.5 mm; and dwell time, 400 msec. Eight and ten weeks post-injury, the GH levels were measured the water maze test and novel object recognition test were performed. CCI rats were divided into normal and decreased GH groups, and further randomly divided into two sub-groups (rhGH treatment and saline vehicle groups). All rats were tested for SYN, BDNF, and TrkB mRNA in the prefrontal cortex and hippocampus by RT-PCR. RESULTS: CCI rats 8 weeks post-injury had cognitive dysfunction regardless of the GH level (P<0.05). rhGH treatment improved cognitive function in CCI rats. There was a positive correlation between the expression of prefrontal BDNF and SYN mRNA in CCI rats after rhGH therapy and the water maze test score (r = 0.773 and 0.534, respectively; P<0.05). Furthermore, the expression of BDNF, TrkB, and SYN mRNA in the hippocampus was negatively correlated with the water maze test score (r = 0.602, 0.773, 0.672, and 0.783, respectively; P<0.05). There was a difference in the expression of hippocampal and prefrontal BDNF, TrkB, and SYN mRNA (P<0.05). CONCLUSION: rhGH treatment had a positive effect on cognitive function, which was more evident in GH-deficient rats. The increased expression of hippocampal and prefrontal BDNF and TrkB mRNA is implicated in rhGH therapy to improve cognitive function. Changes in the expression of hippocampal SYN mRNA following rhGH therapy may also play a role in improving cognitive function.