Sex differences in brain excitability revealed by concurrent iTBS/fNIRS.

Sex differences have been claimed an imperative factor in the optimization of psychiatric treatments. Intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation, is a promising non-invasive treatment option. Here, we investigated whether the real-time neural response to iTBS differs between men and women, and which mechanisms may mediate these differences. To this end, we capitalized on a concurrent iTBS/functional near-infrared spectroscopy setup over the left dorsolateral prefrontal cortex, a common clinical target, to test our assumptions. In a series of experiments, we show (1) a biological sex difference in absolute hemoglobin concentrations in the left dorsolateral prefrontal cortex in healthy participants; (2) that this sex difference is amplified by iTBS but not by cognitive tasks; and (3) that the sex difference amplified by iTBS is modulated by stimulation intensity. These results inform future stimulation treatment optimizations towards precision psychiatry.

Instantaneous effects of prefrontal transcranial magnetic stimulation on brain oxygenation: A systematic review.

This systematic review investigates how prefrontal transcranial magnetic stimulation (TMS) immediately influences neuronal excitability based on oxygenation changes measured by functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS). A thorough understanding of TMS-induced excitability changes may enable clinicians to adjust TMS parameters and optimize treatment plans proactively. Five databases were searched for human studies evaluating brain excitability using concurrent TMS/fMRI or TMS/fNIRS. Thirty-seven studies (13 concurrent TMS/fNIRS studies, 24 concurrent TMS/fMRI studies) were included in a qualitative synthesis. Despite methodological inconsistencies, a distinct pattern of activated nodes in the frontoparietal central executive network, the cingulo-opercular salience network, and the default-mode network emerged. The activated nodes included the prefrontal cortex (particularly dorsolateral prefrontal cortex), insula cortex, striatal regions (especially caudate, putamen), anterior cingulate cortex, and thalamus. High-frequency repetitive TMS most consistently induced expected facilitatory effects in these brain regions. However, varied stimulation parameters (e.g., intensity, coil orientation, target sites) and the inter- and intra-individual variability of brain state contribute to the observed heterogeneity of target excitability and co-activated regions. Given the considerable methodological and individual variability across the limited evidence, conclusions should be drawn with caution.

Neural correlates of fine motor grasping skills: Longitudinal insights into motor cortex activation using fNIRS.

BACKGROUND: Motor learning is essential for performing specific tasks and progresses through distinct stages, including the rapid learning phase (initial skill acquisition), the consolidation phase (skill refinement), and the stable performance phase (skill mastery and maintenance). Understanding the cortical activation dynamics during these stages can guide targeted rehabilitation interventions. METHODS: In this longitudinal randomized controlled trial, functional near-infrared spectroscopy was used to explore the temporal dynamics of cortical activation in hand-related motor learning. Thirty-one healthy right-handed individuals were randomly assigned to perform either easy or intricate motor tasks with their non-dominant hand over 10 days. We conducted 10 monitoring sessions to track cortical activation in the right hemisphere (according to lateralization principles, the primary hemisphere for motor control) and evaluated motor proficiency concurrently. RESULTS: The study delineated three stages of nondominant hand motor learning: rapid learning (days 1 and 2), consolidation (days 3-7), and stable performance (days 8-10). There was a power-law enhancement of motor skills correlated with learning progression. Sustained activation was observed in the supplementary motor area (SMA) and parietal lobe (PL), whereas activation in the right primary motor cortex (M1R) and dorsolateral prefrontal cortex (PFCR) decreased. These cortical activation patterns exhibited a high correlation with the augmentation of motor proficiency. CONCLUSIONS: The findings suggest that early rehabilitation interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), could be optimally directed at M1 and PFC in the initial stages. In contrast, SMA and PL can be targeted throughout the motor learning process. This research illuminates the path for developing tailored motor rehabilitation interventions based on specific stages of motor learning. NEW AND NOTEWORTHY: In an innovative approach, our study uniquely combines a longitudinal design with the robustness of generalized estimating equations (GEEs). With the synergy of functional near-infrared spectroscopy (fNIRS) and the Minnesota Manual Dexterity Test (MMDT) paradigm, we precisely trace the evolution of neural resources during complex, real-world fine-motor task learning. Centering on right-handed participants using their nondominant hand magnifies the intricacies of right hemisphere spatial motor processing. We unravel the brain's dynamic response throughout motor learning stages and its potent link to motor skill enhancement. Significantly, our data point toward the early-phase rehabilitation potential of TMS and transcranial direct current stimulation on the M1 and PFC regions. Concurrently, SMA and PL appear poised to benefit from ongoing interventions during the entire learning curve. Our findings carve a path for refined motor rehabilitation strategies, underscoring the importance of timely noninvasive brain stimulation treatments.

Priming transcranial direct current stimulation for improving hemiparetic upper limb in patients with subacute stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates brain states by applying a weak electrical current to the brain cortex. Several studies have shown that anodal stimulation of the ipsilesional primary motor cortex (M1) may promote motor recovery of the affected upper limb in patients with stroke; however, a high-level clinical recommendation cannot be drawn in view of inconsistent findings. A priming brain stimulation protocol has been proposed to induce stable modulatory effects, in which an inhibitory stimulation is applied prior to excitatory stimulation to a brain area. Our recent work showed that priming theta burst magnetic stimulation demonstrated superior effects in improving upper limb motor function and neurophysiological outcomes. However, it remains unknown whether pairing a session of cathodal tDCS with a session of anodal tDCS will also capitalise on its therapeutic effects. METHODS AND ANALYSIS: This will be a two-arm double-blind randomised controlled trial involving 134 patients 1-6 months after stroke onset. Eligible participants will be randomly allocated to receive 10 sessions of priming tDCS+robotic training, or 10 sessions of non-priming tDCS+robotic training for 2 weeks. The primary outcome is the Fugl-Meyer Assessment-upper extremity, and the secondary outcomes are the Wolf Motor Function Test and Modified Barthel Index. The motor-evoked potentials, regional oxyhaemoglobin level and resting-state functional connectivity between the bilateral M1 will be acquired and analysed to investigate the effects of priming tDCS on neuroplasticity. ETHICS AND DISSEMINATION: The study has been approved by the Research Ethics Committee of the Shanghai Yangzhi Rehabilitation Center (reference number: Yangzhi2023-022) and will be conducted in accordance with the Declaration of Helsinki of 1964, as revised in 2013. TRIAL REGISTRATION NUMBER: ChiCTR2300074681.

The effectiveness and safety of low-intensity transcranial ultrasound stimulation: A systematic review of human and animal studies.

Low-intensity transcranial ultrasound stimulation (LITUS) is a novel non-invasive neuromodulation technique. We conducted a systematic review to evaluate current evidence on the efficacy and safety of LITUS neuromodulation. Five databases were searched from inception to May 31, 2023. Randomized controlled human trials and controlled animal studies were included. The neuromodulation effects of LITUS on clinical or pre-clinical, neurophysiological, neuroimaging, histological and biochemical outcomes, and adverse events were summarized. In total, 11 human studies and 44 animal studies were identified. LITUS demonstrated therapeutic efficacy in neurological disorders, psychiatric disorders, pain, sleep disorders and hypertension. LITUS-related changes in neuronal structure and cortical activity were found. From histological and biochemical perspectives, prominent findings included suppressing the inflammatory response and facilitating neurogenesis. No adverse effects were reported in controlled animal studies included in our review, while reversible headache, nausea, and vomiting were reported in a few human subjects. Overall, LITUS alleviates various symptoms and modulates associated brain circuits without major side effects. Future research needs to establish a solid therapeutic framework for LITUS.

Considerable effects of lateralization and aging in intracortical excitation and inhibition.

Introduction: Findings based on the use of transcranial magnetic stimulation and electromyography (TMS-EMG) to determine the effects of motor lateralization and aging on intracortical excitation and inhibition in the primary motor cortex (M1) are inconsistent in the literature. TMS and electroencephalography (TMS-EEG) measures the excitability of excitatory and inhibitory circuits in the brain cortex without contamination from the spine and muscles. This study aimed to investigate the effects of motor lateralization (dominant and non-dominant hemispheres) and aging (young and older) and their interaction effects on intracortical excitation and inhibition within the M1 in healthy adults, measured using TMS-EMG and TMS-EEG. Methods: This study included 21 young (mean age = 28.1 ± 3.2 years) and 21 older healthy adults (mean age = 62.8 ± 4.2 years). A battery of TMS-EMG measurements and single-pulse TMS-EEG were recorded for the bilateral M1. Results: Two-way repeated-measures analysis of variance was used to investigate lateralization and aging and the lateralization-by-aging interaction effect on neurophysiological outcomes. The non-dominant M1 presented a longer cortical silent period and larger amplitudes of P60, N100, and P180. Corticospinal excitability in older participants was significantly reduced, as supported by a larger resting motor threshold and lower motor-evoked potential amplitudes. N100 amplitudes were significantly reduced in older participants, and the N100 and P180 latencies were significantly later than those in young participants. There was no significant lateralization-by-aging interaction effect in any outcome. Conclusion: Lateralization and aging have independent and significant effects on intracortical excitation and inhibition in healthy adults. The functional decline of excitatory and inhibitory circuits in the M1 is associated with aging.

Deacetylation of chitin oligomers by Fusarium graminearum polysaccharide deacetylase suppresses plant immunity.

Chitin is a long-chain polymer of ß-1,4-linked N-acetylglucosamine that forms rigid microfibrils to maintain the hyphal form and protect it from host attacks. Chitin oligomers are first recognized by the plant receptors in the apoplast region, priming the plant's immune system. Here, seven polysaccharide deacetylases (PDAs) were identified and their activities on chitin substrates were investigated via systematic characterization of the PDA family from Fusarium graminearum. Among these PDAs, FgPDA5 was identified as an important virulence factor and was specifically expressed during pathogenesis. ΔFgpda5 compromised the pathogen's ability to infect wheat. The polysaccharide deacetylase structure of FgPDA5 is essential for the pathogenicity of F. graminearum. FgPDA5 formed a homodimer and accumulated in the plant apoplast. In addition, FgPDA5 showed a high affinity toward chitin substrates. FgPDA5-mediated deacetylation of chitin oligomers prevented activation of plant defence responses. Overall, our results identify FgPDA5 as a polysaccharide deacetylase that can prevent chitin-triggered host immunity in plant apoplast through deacetylation of chitin oligomers.

The N-terminus of a Fusarium graminearum-secreted protein enhances broad-spectrum disease resistance in plants.

Fusarium head blight is a destructive disease caused by Fusarium species. Little is known about the pathogenic molecular weapons of Fusarium graminearum. The gene encoding a small secreted protein, Fg02685, in F. graminearum was found to be upregulated during wheat head infection. Knockout mutation of Fg02685 reduced the growth and development of Fusarium in wheat spikes. Transient expression of Fg02685 or recombinant protein led to plant cell death in a BAK1- and SOBIR1-independent system. Fg02685 was found to trigger plant basal immunity by increasing the deposition of callose, the accumulation of reactive oxygen species (ROS), and the expression of defence-related genes. The Fg02685 signal peptide was required for the plant's apoplast accumulation and induces cell death, indicating Fg02685 is a novel conserved pathogen-associated molecular pattern. Moreover, its homologues are widely distributed in oomycetes and fungal pathogens and induced cell death in tobacco. The conserved α-helical motif at the N-terminus was necessary for the induction of cell death. Moreover, a 32-amino-acid peptide, Fg02685 N-terminus peptide 32 (FgNP32), was essential for the induction of oxidative burst, callose deposition, and mitogen-activated protein kinase signal activation in plants. Prolonged exposure to FgNP32 enhanced the plant's resistance to Fusarium and Phytophthora. This study provides new approaches for an environment-friendly control strategy for crop diseases by applying plant immune inducers to strengthen broad-spectrum disease resistance in crops.

Cortical mapping of active and passive upper limb training in stroke patients and healthy people: A functional near-infrared spectroscopy study.

Active exercise for upper limb training has been widely used to improve hemiplegic upper limb function, and its effect may be boosted by extrinsic visual feedback. The passive movement of the hemiplegic upper limb is also commonly used. We conducted a functional near-infrared spectroscopy experiment to compare cortical activation during the following three conditions: active left upper limb movement (on the hemiplegic sides in stroke patients), with or without extrinsic motor performance visual feedback (LAV, LAnV), and passive left upper limb movement (hemiplegic sides in stroke patients) (LP) in stroke patients and healthy controls. Twenty patients with right hemispheric stroke and 20 healthy controls were recruited for this study. Hemodynamic changes were detected during left upper limb movements (on the hemiplegic sides in stroke patients) under the above three conditions in the sensorimotor cortex (SMC), supplementary motor area (SMA), and premotor cortex (PMC). There was no significant difference in the level of cortical activation between patients with stroke and healthy subjects during the three conditions. Both the LAV and LAnV induced significantly higher activation in the contralateral SMA and PMC than in the LP. Extrinsic visual feedback led to additional activation in the contralateral PMC and SMA, but this was not statistically significant. Our study indicates that active upper-limb movement appears to induce higher cortical activation than that elicited by passive movement in both stroke patients and the healthy population. Extrinsic motor performance in the form of visual feedback provided during active movement may facilitate sensorimotor areas over the contralateral hemisphere.

Brain-Computer Interface-Robot Training Enhances Upper Extremity Performance and Changes the Cortical Activation in Stroke Patients: A Functional Near-Infrared Spectroscopy Study.

Introduction: We evaluated the efficacy of brain-computer interface (BCI) training to explore the hypothesized beneficial effects of physiotherapy alone in chronic stroke patients with moderate or severe paresis. We also focused on the neuroplastic changes in the primary motor cortex (M1) after BCI training. Methods: In this study, 18 hospitalized chronic stroke patients with moderate or severe motor deficits participated. Patients were operated on for 20 sessions and followed up after 1 month. Functional assessments were performed at five points, namely, pre1-, pre2-, mid-, post-training, and 1-month follow-up. Wolf Motor Function Test (WMFT) was used as the primary outcome measure, while Fugl-Meyer Assessment (FMA), its wrist and hand (FMA-WH) sub-score and its shoulder and elbow (FMA-SE) sub-score served as secondary outcome measures. Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) at baseline and after 20 sessions of BCI training. Pearson correlation analysis was used to evaluate functional connectivity (FC) across time points. Results: Compared to the baseline, better functional outcome was observed after BCI training and 1-month follow-up, including a significantly higher probability of achieving a clinically relevant increase in the WMFT full score (ΔWMFT score = 12.39 points, F = 30.28, and P < 0.001), WMFT completion time (ΔWMFT time = 248.39 s, F = 16.83, and P < 0.001), and FMA full score (ΔFMA-UE = 12.72 points, F = 106.07, and P < 0.001), FMA-WH sub-score (ΔFMA-WH = 5.6 points, F = 35.53, and P < 0.001), and FMA-SE sub-score (ΔFMA-SE = 8.06 points, F = 22.38, and P < 0.001). Compared to the baseline, after BCI training the FC between the ipsilateral M1 and the contralateral M1 was increased (P < 0.05), which was the same as the FC between the ipsilateral M1 and the ipsilateral frontal lobe, and the FC between the contralateral M1 and the contralateral frontal lobe was also increased (P < 0.05). Conclusion: The findings demonstrate that BCI-based rehabilitation could be an effective intervention for the motor performance of patients after stroke with moderate or severe upper limb paresis and represents a potential strategy in stroke neurorehabilitation. Our results suggest that FC between ipsilesional M1 and frontal cortex might be enhanced after BCI training. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2100046301.

Effects of virtual reality in improving upper extremity function after stroke: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the effect of virtual reality on arm motor impairment, activity limitation, participation restriction, and quality of life in patients with stroke. To determine potential moderators that affect the efficacy of virtual reality. DATA SOURCES: CINAHL, Medline, PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang Data from inception to October 23, 2021. REVIEW METHODS: Randomized controlled trials that investigated the effect of virtual reality on arm recovery in adult patients with stroke compared to conventional therapy or sham control were included. Physiotherapy Evidence Database Scale was used to assess the methodological quality of each study. RESULTS: Forty studies with 2018 participants were identified. Quality of included studies was fair to high. Virtual reality exhibited better effects on overall arm function (g = 0.28, p < 0.001), motor impairment (g = 0.36, p < 0.001) and activity limitation (daily living) (g = 0.24, p < 0.001) compared with the control group. No significant improvement was observed in participation restriction and activity limitation (specific task). The result for quality of life was described qualitatively. Subgroup analyses demonstrated that immersive virtual reality produced a greater beneficial effect (g = 0.60, p < 0.001). Patients with moderate to severe arm paresis could make more progress after training (g = 0.71, p < 0.001). CONCLUSION: Virtual reality is recommended for improving motor impairment and activities of daily living after stroke and is favorable to patients with moderate to severe paresis. An immersive design could produce greater improvement.

Timing-dependent interaction effects of tDCS with mirror therapy on upper extremity motor recovery in patients with chronic stroke: A randomized controlled pilot study.

This study was a randomized, controlled pilot trial to investigate the timing-dependent interaction effects of dual transcranial direct current stimulation (tDCS) in mirror therapy (MT) for hemiplegic upper extremity in patients with chronic stroke. Thirty patients with chronic stroke were randomly assigned to three groups: tDCS applied before MT (prior-tDCS group), tDCS applied during MT (concurrent-tDCS group), and sham tDCS applied randomly prior to or concurrent with MT (sham-tDCS group). Dual tDCS at 1 mA was applied bilaterally over the ipsilesional M1 (anodal electrode) and the contralesional M1 (cathodal electrode) for 30 min. The intervention was delivered five days per week for two weeks. Upper extremity motor performance was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT), and the Box and Block Test (BBT). Assessments were administered at baseline, post-intervention, and two weeks follow-up. The results indicated that concurrent-tDCS group showed significant improvements in the ARAT in relation to the prior-tDCS group and sham-tDCS group at post-intervention. Besides, a trend toward greater improvement was also found in the FMA-UE for the concurrent-tDCS group. However, no statistically significant difference in the FMA-UE and BBT was identified among the three groups at either post-intervention or follow-up. The concurrent-tDCS seems to be more advantageous and time-efficient in the context of clinical trials combining with MT. The timing-dependent interaction factor of tDCS to facilitate motor recovery should be considered in future clinical application.