Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Motor imagery-based brain-computer interface rehabilitation programs enhance upper extremity performance and cortical activation in stroke patients.

BACKGROUND: The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain-computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. DESIGN: A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. METHODS: Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. RESULTS: A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05). CONCLUSION: In conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients. TRIAL REGISTRATION: The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).

Morphological alterations of contralesional hemisphere relate to functional outcomes after stroke.

The present study aimed to investigate poststroke morphological alterations contralesionally and correlations with functional outcomes. Structural magnetic resonance images were obtained from 27 poststroke patients (24 males, 50.21 ± 10.97 years) and 20 healthy controls (13 males, 46.63 ± 12.18 years). Voxel-based and surface-based morphometry analysis were conducted to detect alterations of contralesional grey matter volume (GMV), cortical thickness (CT), gyrification index (GI), sulcus depth (SD), and fractal dimension (FD) in poststroke patients. Partial correlation analysis was used to explore the relationship between regions with significant structural differences and scores of clinical assessments, including Modified Barthel Index (MBI), Berg Balance Scale (BBS), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Correction for multiplicity was conducted within each parameter and for all tests. GMV significantly decreased in the contralesional motor-related, occipital and temporal cortex, limbic system, and cerebellum lobe (P < 0.01, family-wise error [FWE] correction). Lower CT was found in the contralesional precentral and lingual gyrus (P < 0.01, FWE correction), while lower GI found in the contralesional superior temporal gyrus and insula (P < 0.01, FWE correction). There were significant correlations between GMV of contralesional lingual gyrus and MBI (P = 0.031, r = 0.441), and BBS (P = 0.047, r = 0.409) scores, and GMV of contralesional hippocampus and FMA-UE scores (P = 0.048, r = 0.408). In conclusion, stroke patients exhibited wide grey matter loss and cortical morphological changes in the contralesional hemisphere, which correlated with sensorimotor functions and the ability of daily living.

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

INTRODUCTION: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. METHOD: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. DISCUSSION: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

Focal ischemic stroke modifies microglia-derived exosomal miRNAs: potential role of mir-212-5p in neuronal protection and functional recovery.

BACKGROUND: Ischemic stroke is a severe type of stroke with high disability and mortality rates. In recent years, microglial exosome-derived miRNAs have been shown to be promising candidates for the treatment of ischemic brain injury and exert neuroprotective effects. Mechanisms underlying miRNA dysregulation in ischemic stroke are still being explored. Here, we aimed to verify whether miRNAs derived from exosomes exert effects on functional recovery. METHODS: MiR-212-5p agomir was employed to upregulate miR-212-5p expression in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Western blot analysis, qRT-PCR and immunofluorescence staining and other methods were applied to explore the underlying mechanisms of action of miR-212-5p. RESULTS: The results of our study found that intervention with miR-212-5p agomir effectively decreased infarct volume and restored motor function in MCAO/R rats. Mechanistically, miR-212-5p agomir significantly reduced the expression of PlexinA2 (PLXNA2). Additionally, the results obtained in vitro were similar to those achieved in vivo. CONCLUSION: In conclusion, the present study indicated that PLXNA2 may be a target gene of miR-212-5p, and miR-212-5p has great potential as a target for the treatment and diagnosis of ischemic stroke.

Spatial patterns of intrinsic brain activity and functional connectivity in facial synkinesis patients.

OBJECTIVES: As one of the most objectionable sequelae of facial paralysis, patients with facial synkinesis are more likely to be depressed and have lower quality of life than other facial paralysis patients. However, there is no research on the spatial patterns of intrinsic brain activity and functional connectivity in these patients. The objective of this study was to investigate the spatial patterns and cerebral plasticity of facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age: 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age: 33.21 ± 6.75 years old) were enrolled in this study. resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited decreased ALFF in the fusiform gyrus, lingual gyrus, parahippocampal gyrus, triangular inferior frontal gyrus, precentral gyrus, postcentral gyrus, cingulate gyrus, superior frontal gyrus, precuneus, caudate nucleus and thalamus; decreased ReHo in the cingulate gyrus, superior frontal gyrus, insula, superior temporal gyrus, orbital middle frontal gyrus, caudate nucleus and thalamus; and decreased DC in the frontal lobe, insula, cingulate gyrus, superior temporal gyrus, lenticular putamen, hippocampus and parahippocampal gyrus. We found significant overlap in the superior frontal gyrus across the ALFF, ReHo and DC analyses. CONCLUSIONS: In facial synkinesis patients, the neurological activity in brain areas is reduced and the local synchronization in motion-related brain regions is decreased. The superior frontal gyrus could be a crucial region in the unique spatial patterns of intrinsic brain activity and functional connectivity in these patients.

Structural remodeling secondary to functional remodeling in advanced-stage peripheral facial neuritis.

BACKGROUND: Structural remodeling is a classic manifestation of disease decompensation. Facial synkinesis is the most troubling sequela of peripheral facial neuritis, and its structural remodeling, especially in white matter (WM), is still poorly understood. Therefore, understanding WM microstructure is important for predicting WM pathology and for early intervention in facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age, 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age, 33.21 ± 6.75 years old) were enrolled in this study. rs-fMRI data, diffusion tensor imaging (DTI) data, and Beck's Depression Inventory (BDI) data were collected, and tract-based spatial statistics (TBSS) and voxel-mirrored homotopic connectivity (VMHC) values were used to analyze changes in WM microstructure and interhemispheric coordination. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited significantly lower regional fractional anisotropy (FA) in the genu of the corpus callosum and the body of the corpus callosum, significantly higher regional FA in the retrolenticular part of the internal capsule, and significantly decreased VMHC values bilaterally in the orbital inferior frontal gyri, the fusiform gyri, the superior temporal gyri, the superior frontal gyri, and the supplementary motor areas. Furthermore, a lower regional FA in the genu of the corpus callosum was correlated with higher BDI scores in facial synkinesis patients. CONCLUSION: Structural remodeling, especially changes in white matter microstructure, may be the central mechanism for severe sequelae of peripheral facial neuritis.

Acupuncture Induces Reduction in Limbic-Cortical Feedback of a Neuralgia Rat Model: A Dynamic Causal Modeling Study.

Background: Neuropathic pain after brachial plexus avulsion remained prevalent and intractable currently. However, the neuroimaging study about neural mechanisms or etiology was limited and blurred. Objective: This study is aimed at investigating the effect of electroacupuncture on effective connectivity and neural response in corticolimbic circuitries during implicit processing of nociceptive stimulus in rats with brachial plexus pain. Methods: An fMRI scan was performed in a total of 16 rats with brachial plexus pain, which was equally distributed into the model group and the electroacupuncture group. The analysis of task-dependent data determined pain-related activation in each group. Based on those results, several regions including AMY, S1, and h were recruited as ROI in dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing the propagation of noxious stimuli in regions of interest and horizontal comparison of effective connections between the model and electroacupuncture groups. Results: In both groups, DCM revealed that noxious stimuli were most likely driven by the somatosensory cortex, with bidirectional propagation with the hypothalamus and amygdala and the interactions in them. Also, the 3-month intervention of acupuncture reduced effective connections of h-S1 and AMY-S1. Conclusions: We showed an evidence that a full connection model within the brain network of brachial plexus pain and electroacupuncture intervention reduces effective connectivity from h and AMY to S1. Our study for the first time explored the relationship of involved brain regions with dynamic causal modeling. It provided novel evidence for the feature of the organization of the cortical-limbic network and the alteration caused by acupuncture.

Limbic system plasticity after electroacupuncture intervention in knee osteoarthritis rats.

Knee osteoarthritis (KOA) is characterized by debilitating pain. Electroacupuncture (EA), a traditional Chinese medical therapy, has shown promise in KOA pain management. This study investigated the therapeutic potential of EA in KOA and its impact on limbic system neural plasticity. Sixteen rats were randomly assigned into two groups: EA group and sham-EA group. EA or sham-EA interventions were administered at acupoints ST32 (Futu) and ST36 (Zusanli) for three weeks. Post-intervention resting-state fMRI was scanned, assessing parameters including Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and nodal characterizations of network within limbic system. The results showed that EA was strategically directed towards the limbic system, resulting in discernible alterations in neural activity, FC, and network characteristics. Our findings demonstrate that EA had a significant impact on the limbic system neural plasticity in rats with KOA, presenting a novel nonpharmacological approach for KOA treatment.

Peripheral nerve transfers for dysfunctions in central nervous system injuries: a systematic review.

BACKGROUND: The review highlights recent advancements and innovative uses of nerve transfer surgery in treating dysfunctions caused by central nervous system (CNS) injuries, with a particular focus on spinal cord injury (SCI), stroke, traumatic brain injury, and cerebral palsy. METHODS: A comprehensive literature search was conducted regarding nerve transfer for restoring sensorimotor functions and bladder control following injuries of spinal cord and brain, across PubMed and Web of Science from January 1920 to May 2023. Two independent reviewers undertook article selection, data extraction, and risk of bias assessment with several appraisal tools, including the Cochrane Risk of Bias Tool, the JBI Critical Appraisal Checklist, and SYRCLE's ROB tool. The study protocol has been registered and reported following PRISMA and AMSTAR guidelines. RESULTS: Nine hundred six articles were retrieved, of which 35 studies were included (20 on SCI and 15 on brain injury), with 371 participants included in the surgery group and 192 in the control group. These articles were mostly low-risk, with methodological concerns in study types, highlighting the complexity and diversity. For SCI, the strength of target muscle increased by 3.13 of Medical Research Council grade, and the residual urine volume reduced by more than 100 ml in 15 of 20 patients. For unilateral brain injury, the Fugl-Myer motor assessment (FMA) improved 15.14-26 score in upper extremity compared to 2.35-26 in the control group. The overall reduction in Modified Ashworth score was 0.76-2 compared to 0-1 in the control group. Range of motion (ROM) increased 18.4-80° in elbow, 20.4-110° in wrist and 18.8-130° in forearm, while ROM changed -4.03°-20° in elbow, -2.08°-10° in wrist, -2.26°-20° in forearm in the control group. The improvement of FMA in lower extremity was 9 score compared to the presurgery. CONCLUSION: Nerve transfer generally improves sensorimotor functions in paralyzed limbs and bladder control following CNS injury. The technique effectively creates a 'bypass' for signals and facilitates functional recovery by leveraging neural plasticity. It suggested a future of surgery, neurorehabilitation and robotic-assistants converge to improve outcomes for CNS.

Sports promote brain evolution: a resting-state fMRI study of volleyball athlete.

Background: Long-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear. Method: We conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups. Results: No significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group. Conclusion: This study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registration: Registration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

Effect of aging on the cerebral metabolic mechanism of electroacupuncture treatment in rats with traumatic brain injury.

Objective: Aging has great influence on the clinical treatment effect of cerebrovascular diseases, and evidence suggests that the effect may be associated with age-related brain plasticity. Electroacupuncture is an effective alternative treatment for traumatic brain injury (TBI). In the present study, we aimed to explore the effect of aging on the cerebral metabolic mechanism of electroacupuncture to provide new evidence for developing age-specific rehabilitation strategies. Methods: Both aged (18 months) and young (8 weeks) rats with TBI were analyzed. Thirty-two aged rats were randomly divided into four groups: aged model, aged electroacupuncture, aged sham electroacupuncture, and aged control group. Similarly, 32 young rats were also divided into four groups: young model, young electroacupuncture, young sham electroacupuncture, and young control group. Electroacupuncture was applied to "Bai hui" (GV20) and "Qu chi" (LI11) for 8 weeks. CatWalk gait analysis was then performed at 3 days pre- and post-TBI, and at 1, 2, 4, and 8 weeks after intervention to observe motor function recovery. Positron emission computed tomography (PET/CT) was performed at 3 days pre- and post-TBI, and at 2, 4, and 8 weeks after intervention to detect cerebral metabolism. Results: Gait analysis showed that electroacupuncture improved the forepaw mean intensity in aged rats after 8 weeks of intervention, but after 4 weeks of intervention in young rats. PET/CT revealed increased metabolism in the left (the injured ipsilateral hemisphere) sensorimotor brain areas of aged rats during the electroacupuncture intervention, and increased metabolism in the right (contralateral to injury hemisphere) sensorimotor brain areas of young rats. Results: This study demonstrated that aged rats required a longer electroacupuncture intervention duration to improve motor function than that of young rats. The influence of aging on the cerebral metabolism of electroacupuncture treatment was mainly focused on a particular hemisphere.

Evidence of neuroplasticity with brain-computer interface in a randomized trial for post-stroke rehabilitation: a graph-theoretic study of subnetwork analysis.

Background: Brain-computer interface (BCI) has been widely used for functional recovery after stroke. Understanding the brain mechanisms following BCI intervention to optimize BCI strategies is crucial for the benefit of stroke patients. Methods: Forty-six patients with upper limb motor dysfunction after stroke were recruited and randomly divided into the control group or the BCI group. The primary outcome was measured by the assessment of Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Meanwhile, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in all patients, followed by independent component analysis (ICA) to identify functionally connected brain networks. Finally, we assessed the topological efficiency of both groups using graph-theoretic analysis in these brain subnetworks. Results: The FMA-UE score of the BCI group was significantly higher than that of the control group after treatment (p = 0.035). From the network topology analysis, we first identified seven subnetworks from the rs-fMRI data. In the following analysis of subnetwork properties, small-world properties including γ (p = 0.035) and σ (p = 0.031) within the visual network (VN) decreased in the BCI group. For the analysis of the dorsal attention network (DAN), significant differences were found in assortativity (p = 0.045) between the groups. Additionally, the improvement in FMA-UE was positively correlated with the assortativity of the dorsal attention network (R = 0.498, p = 0.011). Conclusion: Brain-computer interface can promote the recovery of upper limbs after stroke by regulating VN and DAN. The correlation trend of weak intensity proves that functional recovery in stroke patients is likely to be related to the brain's visuospatial processing ability, which can be used to optimize BCI strategies. Clinical Trial Registration: The trial is registered in the Chinese Clinical Trial Registry, number ChiCTR2000034848. Registered 21 July 2020.

Altered Neural Pathways and Related Brain Remodeling: A Rat Study Using Different Nerve Reconstructions.

BACKGROUND: Function recovery is related to cortical plasticity. The brain remodeling patterns induced by alterations in peripheral nerve pathways with different nerve reconstructions are unknown. OBJECTIVE: To explore brain remodeling patterns related to alterations in peripheral neural pathways after different nerve reconstruction surgeries. METHODS: Twenty-four female Sprague-Dawley rats underwent complete left brachial plexus nerve transection, together with the following interventions: no nerve repair (n = 8), grafted nerve repair (n = 8), and phrenic nerve transfer (n = 8). Resting-state functional MR images of brain were acquired at the end of seventh month postsurgery. Amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) were compared among 3 groups. Behavioral observation and electromyography assessed nerve regeneration. RESULTS: Compared with brachial plexus injury group, ALFF and ReHo of left entorhinal cortex decreased in nerve repair and nerve transfer groups. The nerve transfer group showed increased ALFF and ReHo than nerve repair group in left caudate putamen, right accumbens nucleus shell (AcbSh), and right somatosensory cortex. The FC between right somatosensory cortex and bilateral piriform cortices and bilateral somatosensory cortices increased in nerve repair group than brachial plexus injury and nerve transfer groups. The nerve transfer group showed increased FC between right somatosensory cortex and areas including left corpus callosum, left retrosplenial cortex, right parietal association cortex, and right dorsolateral thalamus than nerve repair group. CONCLUSION: Entorhinal cortex is a key brain area in recovery of limb function after nerve reconstruction. Nerve transfer related brain remodeling mainly involved contralateral sensorimotor areas, facilitating directional "shifting" of motor representation.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury: a resting-state functional MRI study.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Modulation of Brain Network Topological Properties in Knee Osteoarthritis by Electroacupuncture in Rats.

Introduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory. Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods. Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P<0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P<0.05). Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.

Mapping the long-term delayed recall-based cortex-hippocampus network constrained by the structural and functional connectome: a case-control multimodal MRI study.

BACKGROUND: Connectome mapping may reveal new treatment targets for patients with neurological and psychiatric diseases. However, the long-term delayed recall based-network with structural and functional connectome is still largely unknown. Our objectives were to (1) identify the long-term delayed recall-based cortex-hippocampus network with structural and functional connectome and (2) investigate its relationships with various cognitive functions, age, and activities of daily living. METHODS: This case-control study enrolled 131 subjects (73 amnestic mild cognitive impairment [aMCI] patients and 58 age- and education-matched healthy controls [HCs]). All subjects completed a neuropsychological battery, activities of daily living assessment, and multimodal magnetic resonance imaging. Nodes of the cortical-hippocampal network related to long-term delayed recall were identified by probabilistic fiber tracking and functional connectivity (FC) analysis. Then, the main and interaction effects of the network on cognitive functions were assessed by a generalized linear model. Finally, the moderating effects of the network on the relationships between long-term delayed recall and clinical features were analyzed by multiple regression and Hayes' bootstrap method. All the effects of cortex-hippocampus network were analyzed at the connectivity and network levels. RESULTS: The result of a generalized linear model showed that the bilateral hippocampus, left dorsolateral superior frontal gyrus, right supplementary motor area, left lingual gyrus, left superior occipital gyrus, left superior parietal gyrus, left precuneus, and right temporal pole (superior temporal gyrus) are the left and right cortex-hippocampus network nodes related to long-term delayed recall (P < 0.05). Significant interaction effects were found between the Auditory Verbal Learning Test Part 5 (AVLT 5) scores and global properties of the left cortex-hippocampus network [hierarchy, clustering coefficient, characteristic path length, global efficiency, local efficiency, Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Significant interaction effects were found between the general cognitive function/executive function/language and global properties of the left cortex-hippocampus network [Sigma and synchronization (P < 0.05 Bonferroni corrected)]. CONCLUSION: This study introduces a novel symptom-based network and describes relationships among cognitive functions, brain function, and age. The cortex-hippocampus network constrained by the structural and functional connectome is closely related to long-term delayed recall.

Dysfunction in the Interaction of Information Between and Within the Bilateral Primary Sensory Cortex.

Background: Interhemispheric and intrahemispheric long-range synchronization and information communication are crucial features of functional integration between the bilateral hemispheres. Previous studies have demonstrated that disrupted functional connectivity (FC) exists in the bilateral hemispheres of patients with carpal tunnel syndrome (CTS), but they did not clearly clarify the phenomenon of central dysfunctional connectivity. This study aimed to further investigate the potential mechanism of the weakened connectivity of primary somatosensory cortex (S1) based on a precise template. Methods: Patients with CTS (n = 53) and healthy control subjects (HCs) (n = 23) participated and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We used FC to investigate the statistical dependency of the whole brain, effective connectivity (EC) to analyze time-dependent effects, and voxel-mirrored homotopic connectivity (VMHC) to examine the coordination of FC, all of which were adopted to explore the change in interhemispheric and intrahemispheric S1. Results: Compared to the healthy controls, we significantly found a decreased strength of the two connectivities in the interhemispheric S1 hand , and the results of EC and VMHC were basically consistent with FC in the CTS. The EC revealed that the information output from the dominant hemisphere to the contralateral hemisphere was weakened. Conclusion: This study found that maladjusted connections between and within the bilateral S1 revealed by these methods are present in patients with CTS. The dominant hemisphere with deafferentation weakens its effect on the contralateral hemisphere. The disturbance in the bilateral S1 provides reliable evidence to understand the neuropathophysiological mechanisms of decreased functional integration in the brains of patients with CTS.

Brain Functional Alteration at Different Stages of Neuropathic Pain With Allodynia and Emotional Disorders.

Neuropathic pain (NeuP), a challenging medical condition, has been suggested by neuroimaging studies to be associated with abnormalities of neural activities in some brain regions. However, aberrancies in brain functional alterations underlying the sensory-discriminative abnormalities and negative emotions in the setting of NeuP remain unexplored. Here, we aimed to investigate the functional alterations in neural activity relevant to pain as well as pain-related depressive-like and anxiety-like behaviors in NeuP by combining amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) analyses methods based on resting-state functional magnetic resonance imaging (rs-fMRI). A rat model of NeuP was established via chronic constriction injury (CCI) of the sciatic nerve. Results revealed that the robust mechanical allodynia occurred early and persisted throughout the entire observational period. Depressive and anxiety-like behaviors did not appear until 4 weeks after injury. When the maximum allodynia was apparent early, CCI rats exhibited decreased ALFF and DC values in the left somatosensory and nucleus accumbens shell (ACbSh), respectively, as compared with sham rats. Both values were significantly positively correlated with mechanical withdrawal thresholds (MWT). At 4 weeks post-CCI, negative emotional states were apparent and CCI rats were noted to exhibit increased ALFF values in the left somatosensory and medial prefrontal cortex (mPFC) as well as increased DC values in the right motor cortex, as compared with sham rats. At 4 weeks post-CCI, ALFF values in the left somatosensory cortex and DC values in the right motor cortex were noted to negatively correlate with MWT and exhibition of anxiety-like behavior on an open-field test (OFT); values were found to positively correlate with the exhibition of depressive-like behavior on forced swimming test (FST). The mPFC ALFF values were found to negatively correlate with the exhibition of anxiety-like behavior on OFT and positively correlate with the exhibition of depressive-like behavior on FST. Our findings detail characteristic alterations of neural activity patterns induced by chronic NeuP and underscore the important role of the left somatosensory cortex, as well as its related networks, in the mediation of subsequent emotional dysregulation due to NeuP.