Modulation of Motor Cortical Activities by Action Observation and Execution in Patients with Stroke: An MEG Study.

Action observation therapy has recently attracted increasing attention; however, the mechanisms through which action observation and execution (AOE) modulate neural activity in stroke patients remain unclear. This study was aimed at investigating the effects of action observation and two types of AOE on motor cortical activations after stroke using magnetoencephalography. Twenty patients with stroke and 20 healthy controls were recruited for the collection of data on the beta oscillatory activity in the primary motor cortex (M1). All participants performed the conditions of resting, observation only, and video observation combined with execution (video AOE). Stroke patients performed one additional condition of affected hand observation combined with execution (affected hand AOE). The relative change index of beta oscillations was calculated, and nonparametric tests were used to examine the differences in conditions. In stroke patients, the relative change index of M1 beta oscillatory activity under the video AOE condition was significantly lower than that under the observation only and affected hand AOE conditions. Moreover, M1 cortical activity did not significantly differ under the observation only and affected hand AOE conditions. For healthy controls, the relative change index under the video AOE condition was significantly lower than that under the observation only condition. In addition, no significant differences in relative change indices were found under the observation only and video AOE conditions between the 2 groups. This study provides new insight into the neural mechanisms underlying AOE, which supports the use of observing videos of normal movements during action observation therapy in stroke rehabilitation.

Xenograft of human umbilical mesenchymal stem cells from Wharton's jelly as a potential therapy for rat pilocarpine-induced epilepsy.

We evaluated the effects of intra-hippocampal transplantation of human umbilical mesenchymal stem cells (HUMSCs) on pilocarpine-treated rats. Sprague-Dawley rats were divided into the following three groups: (1) a normal group of rats receiving only PBS, (2) a status epilepticus (SE) group of rats with pilocarpine-induced SE and PBS injected into the hippocampi, and (3) a SE+HUMSC group of SE rats with HUMSC transplantation. Spontaneous recurrent motor seizures (SRMS) were monitored using simultaneous video and electroencephalographic recordings at two to four weeks after SE induction. The results showed that the number of SRMS within two to four weeks after SE was significantly decreased in SE+HUMSCs rats compared with SE rats. All of the rats were sacrificed on Day 29 after SE. Hippocampal morphology and volume were evaluated using Nissl staining and magnetic resonance imaging. The results showed that the volume of the dorsal hippocampus was smaller in SE rats compared with normal and SE+HUMSCs rats. The pyramidal neuron loss in CA1 and CA3 regions was more severe in the SE rats than in normal and SE+HUMSCs rats. No significant differences were found in the hippocampal neuronal loss or in the number of dentate GABAergic neurons between normal and SE+HUMSCs rats. Compared with the SE rats, the SE+HUMSCs rats exhibited a suppression of astrocyte activity and aberrant mossy fiber sprouting. Implanted HUMSCs survived in the hippocampus and released cytokines, including FGF-6, amphiregulin, glucocorticoid-induced tumor necrosis factors receptor (GITR), MIP-3ß, and osteoprotegerin. In an in vitro study, exposure of cortical neurons to glutamate showed a significant decrease in cell viability, which was preventable by co-culturing with HUMSCs. Above all, the expression of human osteoprotegerin and amphiregulin were significantly increased in the media of the co-culture of neurons and HUMSCs. Our results demonstrate the therapeutic benefits of HUMSC transplantation for the development of epilepsy, which are likely due to the ability of the cells to produce neuroprotective and anti-inflammatory cytokines. Thus, HUMSC transplantation may be an effective therapy in the future.

Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats.

BACKGROUND: Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE). METHODS: SE was induced with pilocarpine in Sprague-Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining. RESULTS: After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895. CONCLUSIONS: An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy.

Mismatch negativity in patients with major depressive disorder: A meta-analysis.

OBJECTIVE: Deficits of mismatch negativity (MMN), a general index of echoic memory function, have been documented in patients with schizophrenia. However, it remains controversial whether patients with major depressive disorder (MDD) demonstrate MMN defects compared with healthy controls (HC). METHODS: After screening 41 potential studies identified in PubMed and Medline, 13 studies consisting of 343 HC and 339 patients with MDD were included in the present meta-analysis. The effect sizes (Hedges's g) with a random-effect and inverse-variance weighted model were estimated for the MMN amplitudes and latencies. The effects of different deviant types (i.e., frequency and duration) and of different illness stages (i.e., acute and chronic) on MMN were also examined. RESULTS: We found that 1) MMN amplitudes (g = 1.273, p < 0.001) and latencies (g = 0.303, p = 0.027) to duration, but not frequency deviants, were significantly impaired in patients with MDD compared to HC; 2), acute patients exhibited lower MMN amplitudes (g = 1.735, p < 0.001) and prolonged MMN latencies (g = 0.461, p = 0.007) for the duration deviants compared to HC. Only the attenuated duration MMN amplitudes were detected in patients with chronic MDD (g = 0.822, p = 0.027); and 3) depressive symptoms did not significantly correlate with MMN responses. CONCLUSIONS: Patients with MDD demonstrated abnormal MMN responses to duration deviants compared to HC. SIGNIFICANCE: Duration MMN may constitute an electrophysiological indicator to differentiate HC from patients with MDD, particularly those in the acute stage.

Reduced coupling of somatosensory gating and gamma oscillation in panic disorder.

Previous studies have reported that patients with panic disorder (PD) exhibited an aberrant level of GABA concentration, an inhibitory neurotransmitter in the human brain. However, it remains substantially unclear whether the inhibitory function regarding the neurophysiological characteristics is altered in this disease. Sensory gating (SG) is considered as an automatic inhibitory function in the sensory cortex. In addition, brain's gamma oscillation within the sensory cortex is another index to reflect inhibitory function. Here we aimed to investigate whether the patients with PD showed altered inhibitory function in the somatosensory system, including the primary (SI) and secondary (SII) somatosensory cortices. A total of 20 healthy controls and 21 patients with PD underwent magnetoencephalographic recordings. Paired-pulse and single-pulse paradigms were used to study SG and gamma oscillations, respectively. There were no significant between-group differences in the SG function in the SI and SII. However, patients with PD demonstrated a reduced gamma power in the SI. Among the healthy individuals, strong associations between SG ratios and gamma frequency values were observed in the SI. However, such a functional relationship disappeared among the patients with PD. We suggested the reduced coupling of SG and gamma oscillation as one of the neural signatures in PD.

Identification of subtypes of anticancer peptides based on sequential features and physicochemical properties.

Anticancer peptides (ACPs) are a kind of bioactive peptides which could be used as a novel type of anticancer drug that has several advantages over chemistry-based drug, including high specificity, strong tumor penetration capacity, and low toxicity to normal cells. As the number of experimentally verified bioactive peptides has increased significantly, various of in silico approaches are imperative for investigating the characteristics of ACPs. However, the lack of methods for investigating the differences in physicochemical properties of ACPs. In this study, we compared the N- and C-terminal amino acid composition for each peptide, there are three major subtypes of ACPs that are defined based on the distribution of positively charged residues. For the first time, we were motivated to develop a two-step machine learning model for identification of the subtypes of ACPs, which classify the input data into the corresponding group before applying the classifier. Further, to improve the predictive power, the hybrid feature sets were considered for prediction. Evaluation by five-fold cross-validation showed that the two-step model trained with sequence-based features and physicochemical properties was most effective in discriminating between ACPs and non-ACPs. The two-step model trained with the hybrid features performed well, with a sensitivity of 86.75%, a specificity of 85.75%, an accuracy of 86.08%, and a Matthews Correlation Coefficient value of 0.703. Furthermore, the model also consistently provides the effective performance in independent testing set, with sensitivity of 77.6%, specificity of 94.74%, accuracy of 88.99% and the MCC value reached 0.75. Finally, the two-step model has been implemented as a web-based tool, namely iDACP, which is now freely available at http://mer.hc.mmh.org.tw/iDACP/ .

Cortical neural activity evoked by bilateral and unilateral mirror therapy after stroke.

OBJECTIVE: This study aimed to investigate the differential effects of bilateral and unilateral mirror therapy (MT) on motor cortical activations in stroke patients by magnetoencephalography (MEG). METHODS: Sixteen stroke patients and 16 right-handed healthy volunteers were recruited. All participants were required to perform 4 conditions: resting, no mirror with bilateral hand movements (Bilateral-No mirror), mirror with bilateral hand movements (Bilateral-Mirror) and mirror with unilateral hand movements (Unilateral-Mirror). Beta oscillatory activities in the primary motor cortex (M1) were collected during each condition using MEG. The percentage change of beta oscillatory activity was calculated for each condition to correct the baseline differences. RESULTS: In the stroke group, the percentage change of M1 beta oscillatory activity significantly decreased more in the Bilateral-Mirror condition than in the Bilateral-No mirror and Unilateral-Mirror conditions. In the healthy group, no significant differences in the percentage change of beta oscillatory activity were found among the 3 conditions. Further, a significant difference in the percentage change of beta oscillatory activity only in the Bilateral-Mirror condition was found between the 2 groups. CONCLUSIONS: This study provides new information on the differential cortical activations modulated by bilateral and unilateral MT. SIGNIFICANCE: Bilateral MT led to greater M1 neural activities than unilateral MT and bilateral movements without a mirror in stroke patients.

Age Effects on Spatiotemporal Dynamics of Response Inhibition: An MEG Study.

Inhibition, the ability to suppress irrelevant information, thoughts or movements, is crucial for humans to perform context-appropriate behaviors. It was suggested that declined cognitive performance in older adults might be attributed to inhibitory deficiencies. Although previous studies have shown an age-associated reduction in inhibitory ability, the understanding regarding its cortical spatiotemporal maps remained limited. Thus, we used a whole-head magnetoencephalography (MEG) to elucidate the age effects on response inhibition, and to explore the brain activation differences in high- and low-performing seniors. We recruited 22 younger and 22 older adults to participate in the visual Go/No-go task. Both behavioral performance and neuromagnetic responses to No-go stimuli were analyzed. The behavioral results showed that the older adults made more false alarm (FA) errors than the younger adults did. The MEG results showed that the seniors exhibited declined cortical activities in middle temporal gyrus (MTG) and delayed activation in MTG, prefrontal cortex (PFC) and pre-supplementary motor area (pre-SMA). Furthermore, among the older adults, more recruitment of the left PFC was found in the high-performers than in the lower-performers. In conclusion, age-related deficiencies in response inhibition were observed in both behavioral performance and neurophysiological measurement. Our results also suggested that frontal recruitment plays a compensatory role in successful inhibition.

Differential motor cortex excitability during observation of normal and abnormal goal-directed movement patterns.

Beta (∼20-Hz) activity induced by median nerve stimulation has been reported to be located in the primary motor cortex (M1) and associated with various movement-related tasks. It has been evident that the ∼20-Hz activity was suppressed more in the observation of goal-directed than non-goal-directed tool use. However, it remains unclear whether this rhythmic activity is further modulated by the observation of normal and abnormal goal-directed hand movements. We recorded neuromagnetic responses in 19 right-handed healthy adults while they kept relaxed (Rest), manipulated a small cube (Act), observed videotapes with normal (Normal) or abnormal (Abnormal) hand actions. The M1 ∼20-Hz rebound powers were quantified through minimum norm estimate and time-frequency analysis at the source level. The results showed that compared to the Rest condition, the M1 ∼20-Hz activities were significantly decreased when subjects observed normal and abnormal hand actions. The suppression was more profound in the Normal than Abnormal condition, indicating a stronger M1 activation during observing graceful, undistorted movement patterns. Our data provided a neurophysiological basis to differentiate the motor cortical activities in the observation of normal and abnormal hand actions. Further research is warranted to verify its clinical benefits in patients with stroke.

Reduced functional connectivity of somatosensory network in writer's cramp patients.

BACKGROUND: The involvement of motor cortex and sensorimotor integration in patients with writer's cramp (WC) has been well documented. However, the exact neurophysiological profile within the somatosensory system, including primary somatosensory cortex (SI), contralateral (SIIc), and ipsilateral (SIIi) secondary somatosensory areas remains less understood. METHODS: This study investigated the neuromagnetic cortical activities of median nerve stimulation in 10 patients with WC and 10 healthy controls (HC). To comprehensively explore all the aspects of somatosensory functioning, we analyzed our data with the minimum norm estimate (MNE), the time-frequency approach with evoked and induced activities, and functional connectivity between SI and SIIc (SI-SIIc), SI and SIIi (SI-SIIi), and SIIc and SIIi (SIIc-SIIi) from theta to gamma oscillations. RESULTS: No significant between-group differences were found in the MNE cortical amplitudes of SI, SIIc, and SIIi. Power strengths of evoked gamma oscillation and induced beta synchronization were also equivalent between WC and HC groups. However, we found significantly reduced theta coherence of SI-SIIi, alpha coherence of SI-SIIi and SIIc-SIIi, as well as beta coherence of SIIc-SIIi in patients with WC. CONCLUSION: Our results suggest the involvement of somatosensory abnormalities, primarily with the form of functional connectivity, in patients with WC.

Reduced motor cortex deactivation in individuals who suffer from writer's cramp.

This study investigated the neuromagnetic activities of self-paced finger lifting task and electrical median nerve stimulation in ten writer's cramp patients and fourteen control subjects. The event-related de/synchronizations (ERD/ERS) of beta-band activity levels were evaluated and the somatosensory cortical activity levels were analyzed using equivalent-current dipole modeling. No significant difference between the patients and control subjects was found in the electrical stimulation-induced beta ERS and electrical evoked somatosensory cortical responses. Movement-related beta ERD did not differ between controls and patients. Notably, the amplitude of the beta ERS after termination of finger movement was significantly lower in the patients than in the control subjects. The reduced movement-related beta ERS might reflect an impairment of motor cortex deactivation. In conclusion, a motor dependent dysregulation of the sensorimotor network seems to be involved in the functional impairment of patients with writer's cramp.

Over-activation in bilateral superior temporal gyrus correlated with subsequent forgetting effect of Chinese words.

We evaluated the subsequent memory and forgotten effects for Chinese using event-related fMRI. Sixteen normal subjects were recruited and performing incidental memory tasks where semantic decision was required during memory encoding. Consistent with previous studies, our results showed bilateral frontal regions as the main locus for the subsequent memory effect. However, contrast between miss and hit responses revealed larger activation in bilateral superior temporal gyrus. We proposed that larger activation in the superior temporal gyrus may reflect alteration of self-monitoring process which resulted in unsuccessful memory encoding for the miss items.

Reduced postmovement cortical inhibition in patients with paroxysmal kinesigenic dyskinesia.

OBJECTIVE: To characterize movement-related neural oscillatory activity and to clarify its neurophysiologic role in paroxysmal kinesigenic dyskinesia (PKD). METHODS: We recorded neuromagnetic event-related desynchronization (ERD) and event-related synchronization (ERS) activities in response to a self-paced finger-lifting task in 16 patients with PKD and 17 healthy controls. RESULTS: The amplitude of α-ERD was comparable between the healthy controls and patients with PKD, whereas either the contralateral or ipsilateral ß-ERS was decreased. The peak latency of contralateral ß-ERS was delayed in patients with PKD. Patients with less frequent dyskinetic attacks demonstrated a larger ipsilateral ß-ERS. Moreover, some patients with PKD revealed a lesser degree of contralateral preponderance of ß-ERS generation. CONCLUSIONS: The present data imply a decreased postmovement inhibition of motor cortex in patients with PKD, and the inhibitory function in the contralateral hemisphere is more affected than that in the ipsilateral hemisphere.

Cardiac neural regulation oscillates with the estrous cycle in freely moving female rats: the role of endogenous estrogens.

Both estrogens levels and sleep/wakefulness states have been separately reported to affect cardiac autonomic regulation. In this study, we examined the integrated effects of the estrous and sleep cycles on cardiac autonomic activity in freely moving adult female rats. Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability. High-frequency power (HF) and low-frequency power to HF ratio are closely correlated with cardiac parasympathetic and sympathetic activity, respectively. Ten days after electrodes were implanted, electroencephalogram, electromyogram, and electrocardiogram were recorded 6 h daily for 12 consecutive days to cover at least two estrous cycles. Estrous-cycle stages were determined using vaginal smears. Sleep cycle-related heart rate variability parameter oscillations were seen in all rats. However, the estrous cyclicity and estrous-cycle-related changes were only observed in the control rats and not in ovariectomized or the estrogen receptor antagonist, tamoxifen, treatment rats. A significantly higher HF was observed in estrous rats compared with diestrous rats or ovariectomized rats no matter whether the rats were asleep or awake. However, a significantly low-frequency power to HF ratio was only observed in quiet sleep (QS) during estrus. All these differences disappeared after treatment with tamoxifen. Our results suggest that estrous-cycle-related changes in cardiac neural regulations can be mainly attributed to endogenous estrogens, and these effects are most obviously manifest during QS. Estrous rats during QS would be equivalent to the late follicular phase of the women menstrual cycle and involve strong vagal tone but weak sympathetic activity.

Combined cardiac sympathetic excitation and vagal impairment in patients with non-organic erectile dysfunction.

OBJECTIVE: Patients with non-organic erectile dysfunction (ED) frequently present with syndromes involving systemic sympathovagal dysfunction. The linkage of ED to cardiac autonomic regulation is not well understood. METHODS: Forty-four men with non-organic ED and 38 healthy age-matched control subjects with ages ranging from 40 years to 69 years were recruited. These two groups were divided into three distinct age categories at 10-year intervals. Patients were divided into three different severity categories, among whom 35 patients received a two-month oral treatment of trazodone. Power spectral analysis of successive R-R intervals (RR) was performed to evaluate the variance (variance of RR-interval values), the high-frequency power (HF), and the ratio of low-frequency power to HF (LF/HF) of their heart rate variability (HRV). RESULTS: Patients exhibited a significantly lower variance and HF, but a higher LF/HF compared to the control group across all age categories. The changes in variance and HF were severity dependent. In addition, all the HRV parameters of the patients with a satisfactory response after treatment have significantly improved. CONCLUSION: The results indicate that patients with non-organic ED had significant cardiac sympathetic hyperactivity and severity-dependent cardiac vagal impairment. SIGNIFICANCE: Non-organic ED may be accompanied by an abnormality in cardiac autonomic regulation.