Observational activation of anterior cingulate cortical neurons coordinates hippocampal replay in social learning.

Social learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are activated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during sharp-wave ripples and spatial contents of hippocampal replay prior to self-running. The results support that ACC neurons involved in decisions during self-running are reactivated during observation and coordinate hippocampal replay to guide subsequent spatial navigation.

Tetrode recording of rat CA1 place cells in an observational spatial working memory task.

Social observation facilitates spatial learning by activation of hippocampal place cell patterns. Here, we describe an observational spatial working memory task to investigate the neural circuits underlying observational learning. This approach trains observer rats to learn to run a T-maze by observing a demonstrator's spatial trajectory while recording their hippocampal CA1 place cell activities in a course of several hours. The protocol provides a tool to study neural activities at population level in a social setting. For complete details on the use and execution of this protocol, please refer to Mou et al. (2021).

High-Frequency Repetitive Transcranial Magnetic Stimulation Regulates Astrocyte Activation by Modulating the Endocannabinoid System in Parkinson's Disease.

Reactive astrogliosis and the over-production of proinflammatory factors are key pathogenetic processes in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS), a promising noninvasive technique in treating PD, has been shown to alleviate neuroinflammation. However, high-frequency (HF) and low-frequency (LF) rTMS, which one produces better therapeutic and anti-inflammatory effects, and the underlying mechanism have yet to be determined. The efficacies of HF, LF, and sham rTMS on the survival of dopaminergic (DA) neurons, improvement of motor function, and downregulation of proinflammatory factors were compared in 6-hydroxydopamine (6-OHDA) rat model. Then we investigated the role of endocannabinoid (eCB) system in the inhibition of astrocyte activation between HF vs LF rTMS. The results showed that HF rTMS daily for 4 weeks produced stronger anti-inflammatory and neuroprotective effects. ECB receptor 2 (CB2R) but not receptor 1 (CB1R) expressions were substantially elevated in the GFAP-positive reactive astrocytes of the rat brains with 6-OHDA or LPS insults. Increased anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were also observed. Interestingly, the elevated CB2R, AEA and 2-AG, and the increased GFAP expression could be all significantly suppressed by HF rTMS, but not by LF rTMS. This effect was also confirmed in cell culture. Of note, selective agonism of CB2R was able to reverse HF rTMS-mediated activation of extracellular regulated kinase1/2 (Erk1/2) and suppression of GFAP expression, while selective antagonism of CB2R sustained these effects. This study indicates that the modulation of eCB/CB2R is a potential mechanism for the greater effectiveness of HF rTMS on the inhibition of astrogliosis.

Effects of Training with a Brain-Computer Interface-Controlled Robot on Rehabilitation Outcome in Patients with Subacute Stroke: A Randomized Controlled Trial.

INTRODUCTION: Stroke is always associated with a difficult functional recovery process. A brain-computer interface (BCI) is a technology which provides a direct connection between the human brain and external devices. The primary aim of this study was to determine whether training with a BCI-controlled robot can improve functions in patients with subacute stroke. METHODS: Subacute stroke patients aged 32-68 years with a course of 2 weeks to 3 months were randomly assigned to the BCI group or to the sham group for a 4-week course. The primary outcome measures were Loewenstein Occupational Therapy Cognitive Assessment (LOCTA) and Fugl-Meyer Assessment for Lower Extremity (FMA-LE). Secondary outcome measures included Fugl-Meyer Assessment for Balance (FMA-B), Functional Ambulation Category (FAC), Modified Barthel Index (MBI), serum brain-derived neurotrophic factor (BDNF) levels and motor-evoked potential (MEP). RESULTS: A total of 28 patients completed the study. Both groups showed a significant increase in mean LOCTA (sham: P < 0.001, Cohen's d =  - 2.972; BCI: P < 0.001, Cohen's d =  - 4.266) and FMA-LE (sham: P < 0.001, Cohen's d =  - 3.178; BCI: P < 0.001, Cohen's d =  - 3.063) scores. The LOCTA scores in the BCI group were 14.89% higher than in the sham group (P = 0.049, Cohen's d =  - 0.580). There were no significant differences between the two groups in terms of FMA-B (P = 0.363, Cohen's d =  - 0.252), FAC (P = 0.363), or MBI (P = 0.493, Cohen's d =  - 0.188) scores. The serum levels of BDNF were significantly higher within the BCI group (P < 0.001, Cohen's d =  - 1.167), and the MEP latency decreased by 3.75% and 4.71% in the sham and BCI groups, respectively. CONCLUSION: Training with a BCI-controlled robot combined with traditional physiotherapy promotes cognitive function recovery, and enhances motor functions of the lower extremity in patients with subacute stroke. These patients also showed increased secretion of BDNF. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR-INR-17012874.

Observational learning promotes hippocampal remote awake replay toward future reward locations.

The neural circuit mechanisms underlying observational learning, learning through observing the behavior of others, are poorly understood. Hippocampal place cells are important for spatial learning, and awake replay of place cell patterns is involved in spatial decisions. Here we show that, in observer rats learning to run a maze by watching a demonstrator's spatial trajectories from a separate nearby observation box, place cell patterns during self-running in the maze are replayed remotely in the box. The contents of the remote awake replay preferentially target the maze's reward sites from both forward and reverse replay directions and reflect the observer's future correct trajectories in the maze. In contrast, under control conditions without a demonstrator, the remote replay is significantly reduced, and the preferences for reward sites and future trajectories disappear. Our results suggest that social observation directs the contents of remote awake replay to guide spatial decisions in observational learning.

LSD degrades hippocampal spatial representations and suppresses hippocampal-visual cortical interactions.

Lysergic acid diethylamide (LSD) produces hallucinations, which are perceptions uncoupled from the external environment. How LSD alters neuronal activities in vivo that underlie abnormal perceptions is unknown. Here, we show that when rats run along a familiar track, hippocampal place cells under LSD reduce their firing rates, their directionality, and their interaction with visual cortical neurons. However, both hippocampal and visual cortical neurons temporarily increase firing rates during head-twitching, a behavioral signature of a hallucination-like state in rodents. When rats are immobile on the track, LSD enhances cortical firing synchrony in a state similar to the wakefulness-to-sleep transition, during which the hippocampal-cortical interaction remains dampened while hippocampal awake reactivation is maintained. Our results suggest that LSD suppresses hippocampal-cortical interactions during active behavior and during immobility, leading to internal hippocampal representations that are degraded and isolated from external sensory input. These effects may contribute to LSD-produced abnormal perceptions.

LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels.

BACKGROUND: Manipulation of neural stem and progenitor cells (NSPCs) is critical for the successful treatment of spinal cord injury (SCI) by NSPC transplantation, since their differentiation into neurons and oligodendrocytes can be inhibited by factors present in inflamed myelin. In this study, we examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, the underlying mechanisms of action, and the functional recovery of mice after transplantation of manipulated cells. METHODS: sp-NSPCs were harvested from female adult C57/BL6 mice after SCI induced with an NYU impactor. These cells were infected with lentiviral vectors containing LINGO-1 shRNA sequence or a scrambled control and transplanted into SCI mice. Tuj-1- and GFAP-positive cells were assessed by immunofluorescence staining. Wnt5a, p-JNK, JNK, and ß-catenin expression was determined by Western blot and RT-qPCR. miRNAs were sequenced to detect changes in miRNA expression. Motor function was evaluated 0-35 days post-surgery by means of the Basso Mouse Scale (BMS) and by the rotarod performance test. RESULTS: We discovered that LINGO-1 shRNA increased neuronal differentiation of sp-NSPCs while decreasing astrocyte differentiation. These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels. miRNA-sequence analysis demonstrated that miR-15b-3p was a downstream mediator of LINGO-1 which suppressed Wnt5a expression. Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery. CONCLUSIONS: LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Analgesic Effects of Navigated Repetitive Transcranial Magnetic Stimulation in Patients With Acute Central Poststroke Pain.

INTRODUCTION: Central poststroke pain (CPSP) develops commonly after stroke, which impairs the quality of life, mood, and social functioning. Current pharmacological approaches for the treatment of CPSP are not satisfactory. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique which has been recommended for the treatment of chronic CPSP. However, few studies have evaluated the analgesic effects of rTMS in patients with acute neuropathic pain after stroke. METHODS: We evaluated the analgesic effects of rTMS applied over the upper extremity area of the motor cortex (M1) in patients with acute CPSP. Forty patients were randomized to receive either rTMS (10 Hz, 2000 stimuli) (n = 20) or a sham intervention (n = 20) for 3 weeks. The Numeric Rating Scale (NRS), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2, Chinese version), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), brain-derived neurotrophic factor (BDNF) levels, and motor-evoked potentials (MEP) were analyzed at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. RESULTS: Significant treatment-time interactions were found for pain intensity. Compared with the sham group, the NRS and SF-MPQ-2 scores were significantly lower on the seventh day of treatment in the rTMS group (P < 0.001, Cohen's d = 1.302) (P = 0.003, Cohen's d = 0.771), and this effect lasted until the third week (P = 0.001, Cohen's d = 0.860) (P = 0.027, Cohen's d = 0.550). The HAM-A and HAM-D scores did not change in the rTMS group when compared with the sham group (P = 0.341, Cohen's d = 0.224) (P = 0.356, Cohen's d = 0.217). The serum BDNF levels were significantly higher in the treated group (P = 0.048, Cohen's d = -0.487), and the resting motor threshold (RMT) decreased by 163.65%. CONCLUSION: Our findings indicate that rTMS applied over the upper extremity area of the motor cortex can effectively alleviate acute CPSP, possibly by influencing cortical excitability and serum BDNF secretion. TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of China: Reg. No. ChiCTR-INR-17012880.

Analgesic Effects of Directed Repetitive Transcranial Magnetic Stimulation in Acute Neuropathic Pain After Spinal Cord Injury.

OBJECTIVES: Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. METHODS: A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. RESULTS: The analysis showed significant treatment-time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen's d = 1.135; P = 0.006, Cohen's d = 0.616) and after one week (P < 0.001, Cohen's d = 0.846; P = 0.012, Cohen's d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen's d = 0.539; P = 0.009, Cohen's d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen's d = 0.464). CONCLUSIONS: These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.

Clinical outcomes of treatment with cage-shaped demineralized bone plus local bone grafts vs. autogenous iliac crest bone grafts in instrumented single-level lumbar fusion: A retrospective cohort study.

The aim of the present study was to compare the clinical outcomes of cage-shaped demineralized bone plus local bone grafts (CDBLG) with those of autogenous iliac crest bone grafts (ICBG) implanted for the treatment of single-level lumbar intervertebral disc degenerative diseases. A total of 69 cases of degenerative spinal disorder treated between January 2011 and December 2013 were retrospectively analyzed. Of these, 44 were treated with CDBLG and 25 with autogenous ICBG. All fusions were instrumented single level. Fusion was assessed after 6, 12 and 24 months by X-ray and CT scans post-operatively. Clinical outcomes were determined during follow-up and assessments included the Oswestry Disability Index, Visual Analogue Scale for back and leg pain and the Short Form-36 general health survey physical component summary. The results indicated that the overall fusion rate at 24 months post-operatively was higher in the ICBG group compared with that in the CDBLG group, although not significantly (P>0.05). All other outcome measures were significantly improved in the two groups after the surgery (P<0.05), but no significant differences were observed between the two groups (P>0.05). Blood loss and mean duration of surgery in the CDBLG group were significantly lower compared with those in the ICBG group (P<0.05). In conclusion, CDBLG achieved a similar fusion rate and clinical outcome as ICBG but was associated with significantly reduced blood loss and mean duration of surgery. In conclusion, the present study provided CDBLG bone graft as an alternative option for single-level fusion.

Analgesia-enhancing effects of repetitive transcranial magnetic stimulation on neuropathic pain after spinal cord injury:An fNIRS study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for chronic intractable neuropathic pain in patients with spinal cord injury (SCI). However, the analgesia-enhancing effects of rTMS on conventional interventions (e.g., medications), and the underlying mechanisms remain poorly understood. OBJECTIVE: To investigate the enhancement of analgesia and change of cortex activation by rTMS treatment on neuropathic pain following SCI. METHODS: A double-blind, sham-controlled, clinical trial was performed. Twenty-one patients with neuropathic pain after SCI were randomized (2:1) to receive a session of rTMS (10 Hz, a total of 1200 pulses at an intensity of 80% resting motor threshold) or sham treatment over the left primary motor cortex (M1) corresponding to the hand area daily for six weeks with a one-day interval per week. At T0 (before rTMS treatment), T1 (after the first session rTMS), T2 (after one week), T3 (after two weeks), T4 (after four weeks) and T5 (after six weeks), activations in the bilateral M1, primary somatosensory cortex (S1), premotor cortex (PMC) and prefrontal cortex (PFC) during the handgrip task were measured using functional near-infrared spectroscopy (fNIRS). In addition, the numerical rating scale (NRS) was used to assess pain. RESULTS: The pain intensity or activation in PFC, PMC, M1 or S1 was not remarkably changed at T1. Along with the time, the pain intensity gradually decreased in both the rTMS and sham groups. The real rTMS, compared with the sham, showed more pain relief from two weeks (T3) to six weeks (T5), and the activations of the motor-related areas M1 and PMC were remarkably suppressed. CONCLUSIONS: The findings of this preliminary study with a small patient sample suggest that the analgesia-enhancing effects of high-frequency rTMS might be related with the amelioration of M1 and PMC hypersensitivity, shedding light upon the clinical treatment of SCI-related neuropathic pain.

A Convolutional Neural Network for the Detection of Asynchronous Steady State Motion Visual Evoked Potential.

A key issue in brain-computer interface (BCI) is the detection of intentional control (IC) states and non-intentional control (NC) states in an asynchronous manner. Furthermore, for steady-state visual evoked potential (SSVEP) BCI systems, multiple states (sub-states) exist within the IC state. Existing recognition methods rely on a threshold technique, which is difficult to realize high accuracy, i.e., simultaneously high true positive rate and low false positive rate. To address this issue, we proposed a novel convolutional neural network (CNN) to detect IC and NC states in a SSVEP-BCI system for the first time. Specifically, the steady-state motion visual evoked potentials (SSMVEP) paradigm, which has been shown to induce less visual discomfort, was chosen as the experimental paradigm. Two processing pipelines were proposed for the detection of IC and NC states. The first one was using CNN as a multi-class classifier to discriminate between all the states in IC and NC state (FFT-CNN). The second one was using CNN to discriminate between IC and NC states, and using canonical correlation analysis (CCA) to perform classification tasks within the IC (FFT-CNN-CCA). We demonstrated that both pipelines achieved a significant increase in accuracy for low-performance healthy participants when traditional algorithms such as CCA threshold were used. Furthermore, the FFT-CNN-CCA pipeline achieved better performance than the FFT-CNN pipeline based on the stroke patients' data. In summary, we showed that CNN can be used for robust detection in an asynchronous SSMVEP-BCI with great potential for out-of-lab BCI applications.

rTMS Regulates the Balance Between Proliferation and Apoptosis of Spinal Cord Derived Neural Stem/Progenitor Cells.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique that uses electromagnetic fields to stimulate the brain. rTMS can restore an impaired central nervous system and promote proliferation of neural stem/progenitor cells (NSPCs), but optimal stimulus parameters and mechanisms underlying these effects remain elusive. The purpose of this study is to investigate the effect of different rTMS stimulus parameters on proliferation and apoptosis of spinal cord-derived NSPCs, the expression of brain-derived neurotrophic factor (BDNF) after rTMS, and the potentially underlying pathways. NSPCs were isolated from mice spinal cord and stimulated by different frequencies (1/10/20 Hz), intensities (0.87/1.24/1.58 T), and number of pulses (400/800/1,500/3,000) once a day for five consecutive days. NSPC proliferation was analyzed by measuring the neurosphere diameter and Brdu staining, apoptosis was detected by cell death enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and NSPC viability was assessed by cell counting kit-8 assay. We found that specific parameters of frequency (1/10/20 Hz), intensity (1.24/1.58 T), and number of pulses (800/1,500/3,000) promote proliferation and apoptosis (p < 0.05 for all), but 20 Hz, 1.58 T, and 1,500 pulses achieved the optimal response for the NSPC viability. In addition, rTMS significantly promoted the expression of BDNF at the mRNA and protein level, while also increasing Akt phosphorylation (Thr308 and Ser473; p < 0.05). Overall, we identified the most appropriate rTMS parameters for further studies on NSPCs in vitro and in vivo. Furthermore, the effect of magnetic stimulation on NSPC proliferation might be correlated to BDNF/Akt signaling pathway.

Comparing Mouse and Rat Hippocampal Place Cell Activities and Firing Sequences in the Same Environments.

Hippocampal place cells are key to spatial representation and spatial memory processing. They fire at specific locations in a space (place fields) and fire in precise patterns during theta sequences and during ripple-associated replay events. These phenomena have been extensively studied in rats, but to a less extent in mice. The availability of versatile genetic manipulations gives mice an advantage for place cell studies. However, it is unknown how place fields and place cell sequences in the same environment differ between mice and rats. Here, we provide a quantitative comparison in place field properties, as well as theta sequences and replays, between rats and mice as they ran on the same novel track and as they rested afterwards. We found that place cells in mice display less spatial specificity with more but smaller place fields. Theta oscillations, theta phase precession and aspects of theta sequences in mice are similar as those in rats. The ripple-associated replay, however, is relatively rare during stopping on the novel track in mice. The replay is present during resting after the track running, but is weaker in mice than the replay in rats. Our results suggest that place cells in mice and rats are qualitatively similar, but with substantial quantitative differences.

Value of using the international classification of functioning, disability, and health for stroke rehabilitation assessment: A multicenter clinical study.

This study aimed to evaluate the efficiency of the International Classification of Functioning, Disability, and Health (ICF) in stroke rehabilitation assessment in China and to identify correlations between the ICF and several commonly used clinical assessment instruments for stroke.In total, 52 hospitals and 5 premier rehabilitation and neurology research centers participated in this cross-sectional multicenter clinical study. A total of 2822 stroke patients admitted to a neurology or rehabilitation department of a participating medical center between July 2012 and June 2014 were included. The ICF checklist contains 4 parts with 128 two-level items: body functions, body structures, activities and participation, and environmental factors. We analyzed the results of ICF assessments and determined whether correlations existed between the various items of the ICF and several commonly used clinical assessment instruments.In all but 3 instances, the scores for the ICF-b-body function, ICF-s-body structure-degree of impairment, ICF-s-body structure-impairment location, ICF-d-activity performance, ICF-d-ability performance, ICF-e-facilitator, and ICF-e-barrier correlated significantly (P < .05) with the scores for the commonly used clinical assessment instruments.The ICF checklist is a new rehabilitation assessment instrument that is compatible with commonly used clinical assessment scales for stroke and can be used in combination with these scales.

Acute compartment syndrome of the leg due to infection following an insect bite: A case report.

RATIONALE: Acute compartment syndrome is a highly aggressive condition, which needs rapid diagnosis and surgical emergency. Most cases are caused by trauma, fractures, surgeries, or vascular injury, while other causes are easily misdiagnosed. PATIENTS CONCERNS: A 29-year-old female, with a medical history of an insect bite on the left calf but not recent trauma, was admitted to the hospital due to the swelling and pain around the bite area. DIAGNOSES: Acute compartment syndrome of the lower leg. INTERVENTIONS: After admission, she developed septic shock symptoms, given intravenous antibiotics treatments. However, the condition worsened with increasing pain, loss of sensation, tense swelling, and severe pain to any stretch of the tissues. Thus the patient received fasciotomy followed by repeat and thorough debridement. After the wounds healed completely, systematic rehabilitation was performed for three weeks. OUTCOMES: After three months of follow-up, the patient is able to walk, and moves up and down the stairs, independently. LESSONS: Our case highlights the possibility of acute compartment syndrome caused by insect bites when the patient presents with the signs of the condition, and the importance of earlier rehabilitation interventions to improve the functional outcome post operation.

Impaired spatial memory codes in a mouse model of Rett syndrome.

The Mecp2+/- mouse model recapitulates many phenotypes of patients with Rett syndrome (RTT), including learning and memory deficits. It is unknown, however, how the disease state alters memory circuit functions in vivo in RTT mice. Here we recorded from hippocampal place cells, which are thought to encode spatial memories, in freely moving RTT mice and littermate controls. We found that place cells in RTT mice are impaired in their experience-dependent increase of spatial information. This impairment is accompanied by an enhanced baseline firing synchrony of place cells within ripple oscillations during rest, which consequently occludes the increase in synchrony after a novel experience. Behaviorally, contextual memory is normal at short but not long time scale in RTT mice. Our results suggest that hypersynchrony interferes with memory consolidation and leads to impaired spatial memory codes in RTT mice, providing a possible circuit mechanism for memory deficits in Rett Syndrome.

Effects of combining high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke.

BACKGROUND: Both high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency rTMS (LF-rTMS) are reported to benefit upper limb motor function rehabilitation in patients with stroke. However, the efficacy of combining LF- and HF-rTMS (LF-HF rTMS) has not been adequately explored, especially in the early phase of stroke. OBJECTIVE: To compare the effects of LF- and LF-HF rTMS on the upper limb motor function in the early phase post stroke. METHODS: Sixty-two patients were randomly assigned to three groups: LF-rTMS group (1 Hz rTMS to the contralesional hemisphere), LF-HF rTMS group (1 Hz rTMS to the contralesional hemisphere followed by 10 Hz rTMS to the lesional hemisphere) and sham group. The patients received the same conventional rehabilitation accompanied with sessions of rTMS for 15 consecutive days. The upper limb motor function was evaluated using the Fugl-Meyer Assessment (FMA) and the Wolf Motor Function Test (WMFT) before the first session, after the last session, and at 3 months after the last session. RESULTS: All patients finished the study without any adverse reaction. Three groups exhibited improvement in terms of the FMA score and the log WMFT time at the end of the treatment and 3 months later. Better improvement was found in the LF-HF rTMS group than in the LF-rTMS and sham groups. CONCLUSION: The results indicated that both LF- and LF-HF rTMS were effective in promoting upper limb motor recovery in patients with acute stroke. Combining HF- and LF-rTMS protocol in the present study is tolerable and more beneficial for motor improvement than the unilateral use of LF-rTMS alone.

Regulation of Locomotor activity in fed, fasted, and food-restricted mice lacking tissue-type plasminogen activator.

BACKGROUND: Circadian rhythms of physiology and behavior are driven by a circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This clock is synchronized to environmental day/night cycles by photic input, which is dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from plasminogen by the enzyme tissue-type plasminogen activator (tPA). In this study, we evaluate circadian function in mice lacking functional tPA. RESULTS: tPA-/- mice have normal circadian periods, but show decreased nocturnal wheel-running activity. This difference is eliminated or reversed on the second day of a 48-h fast. Similarly, when placed on daily cycles of restricted food availability the genotypic difference in total wheel-running activity disappears, and tPA-/- mice show equivalent amounts of food anticipatory activity to wild type mice. CONCLUSIONS: These data suggest that tPA regulates nocturnal wheel-running activity, and that tPA differentially affects SCN-driven nocturnal activity rhythms and activity driven by fasting or temporal food restriction.