Neural Plasticity最新文献

Purpose: This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables.

Materials and methods: Structural MRI of brain was acquired in 24 complete thoracic SCI patients (38.50 ± 11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants (38.38 ± 10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients' clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender.

Results: Compared with healthy controls, SCI patients showed higher SDS score (t = 4.392 and p < 0.001). In the VBM analysis, significant GMV reduction was found in the left middle frontal cortex, right superior orbital frontal cortex (OFC), and left inferior OFC. No significant difference was found in global network properties between SCI patients and healthy controls. In the regional network properties, significantly higher betweenness centrality (BC) was noted in the right anterior cingulum cortex (ACC) and left inferior OFC and higher nodal degree and efficiency in bilateral middle OFCs, while decreased BC was noted in the right putamen in SCI patients. Only negative correlation was found between GMV of right middle OFC and SDS score in SCI patients (r = -0.503 and p = 0.017), while no significant correlation between other abnormal brain regions and any of the clinical variables (all p > 0.05).

Conclusions: SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

Background: Diabetes-associated cognitive decline (DACD) is one of the nervous system dysfunctions induced by diabetes mellitus with cognitive impairment as the major symptom. In a previous preliminary proteomic study, we found that endoplasmic reticulum processing and PI3K-Akt signaling pathway might be impaired in DACD pathogenesis. In addition, growth factor receptor-bound protein 2 might be a crucial protein as a molecular target of the neuroprotective effects of ZiBuPiYin recipe (ZBPYR).

Methods: In this study, 6-8 weeks aged db/db mice were treated with excipients or ZBPYR for 6 weeks. Body weight and RBG were recorded weekly. Oral glucose tolerance and insulin tolerance tests were used to assess insulin sensitivity. Morris water maze (MWM) tests were used to assess memory function. The expression of Grb2, Gab2, Akt, and GSK3β in mouse hippocampus and cerebral cortex were analyzed by Western blotting.

Results: ZBPYR not only significantly reduced RGB and improved glucose tolerance and insulin resistance, but also improved spatial cognition in DACD mice. The expression of Grb2 and Gab2 in hippocampus and cerebral cortex of db/db mice was upregulated after treated with ZBPYR, and then affected the PI3K/Akt signaling pathway, and inhibited GSK3β overactivity.

Conclusions: This study showed that ZBPYR could enhance the memory and learning ability of db/db mice. Such neuroprotective effect might be related to the activation of Grb2-PI3K/Akt signaling which might provide a novel therapeutic target for the clinical treatment of DACD.

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.

Mental fatigue is a common psychobiological state elected by prolonged cognitive activities. Although, the performance and the disadvantage of the mental fatigue have been well known, its connectivity among the multiareas of the brain has not been thoroughly studied yet. This is important for the clarification of the mental fatigue mechanism. However, the common method of connectivity analysis based on EEG cannot get rid of the interference from strong noise. In this paper, an adaptive feature extraction model based on stacked denoising autoencoder has been proposed. The signal to noise ratio of the extracted feature has been analyzed. Compared with principal component analysis, the proposed method can significantly improve the signal to noise ratio and suppress the noise interference. The proposed method has been applied on the analysis of mental fatigue connectivity. The causal connectivity among the frontal, motor, parietal, and visual areas under the awake, fatigue, and sleep deprivation conditions has been analyzed, and different patterns of connectivity between conditions have been revealed. The connectivity direction under awake condition and sleep deprivation condition is opposite. Moreover, there is a complex and bidirectional connectivity relationship, from the anterior areas to the posterior areas and from the posterior areas to the anterior areas, under fatigue condition. These results imply that there are different brain patterns on the three conditions. This study provides an effective method for EEG analysis. It may be favorable to disclose the underlying mechanism of mental fatigue by connectivity analysis.

Objective: To investigate the functional reorganization of the motor network after repetitive transcranial magnetic stimulation (rTMS) in stroke patients with motor dysfunction and the distinction between high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS).

Methods: Thirty-three subcortical stroke patients were enrolled and assigned to the HF-rTMS group, LF-rTMS group, and sham group. Each patient of rTMS groups received either 10.0 Hz rTMS over the ipsilesional primary motor cortex (M1) or 1.0 Hz rTMS over the contralesional M1 for 10 consecutive days. A resting-state functional magnetic resonance imaging (fMRI) scan and neurological examinations were performed at baseline and after rTMS. The motor network and functional connectivities intramotor network with the core brain regions including the bilateral M1, premotor area (PMA), and supplementary motor area (SMA) were calculated. Comparisons of functional connectivities and Pearson correlation analysis between functional connectivity changes and behavioral improvement were calculated.

Results: Significant motor improvement was found after rTMS in all groups which was larger in two rTMS groups than in the sham group. The functional connectivities of the motor network were significantly increased in bilateral M1, SMA, and contralesional PMA after real rTMS. These changes were only detected in the regions of the ipsilesional hemisphere in the HF-rTMS group and in the regions of the contralesional hemisphere in the LF-rTMS group. Significantly changed functional connectivities of the intramotor network were found between the ipsilesional M1 and SMA and contralesional PMA, between contralesional M1 and contralesional SMA, between contralesional SMA and ipsilesional SMA and contralesional PMA in the HF-rTMS group in which the changed connectivity between ipsilesional M1 and contralesional PMA was obviously correlated with the motor improvement. In addition, the functional connectivity of the intramotor network between ipsilesional M1 and contralesional PMA was significantly higher in the HF-rTMS group than in the LF-rTMS group.

Conclusion: Both HF-rTMS and LF-rTMS have a positive effect on motor recovery in patients with subcortical stroke and could promote the reorganization of the motor network. HF-rTMS may contribute more to the functional connectivity reorganization of the ipsilesional motor network and realize greater benefit to the motor recovery.

Gamma oscillation in neural circuits is believed to associate with effective learning in the brain, while the underlying mechanism is unclear. This paper aims to study how spike-timing-dependent plasticity (STDP), a typical mechanism of learning, with its interaction with gamma oscillation in neural circuits, shapes the network dynamics properties and the network structure formation. We study an excitatory-inhibitory (E-I) integrate-and-fire neuronal network with triplet STDP, heterosynaptic plasticity, and a transmitter-induced plasticity. Our results show that the performance of plasticity is diverse in different synchronization levels. We find that gamma oscillation is beneficial to synaptic potentiation among stimulated neurons by forming a special network structure where the sum of excitatory input synaptic strength is correlated with the sum of inhibitory input synaptic strength. The circuit can maintain E-I balanced input on average, whereas the balance is temporal broken during the learning-induced oscillations. Our study reveals a potential mechanism about the benefits of gamma oscillation on learning in biological neural circuits.

Postinhibitory facilitation (PIF) of neural firing presents a paradoxical phenomenon that the inhibitory effect induces enhancement instead of reduction of the firing activity, which plays important roles in sound location of the auditory nervous system, awaited theoretical explanations. In the present paper, excitability and threshold mechanism for the PIF phenomenon is presented in the Morris-Lecar model with type I, II, and III excitabilities. Firstly, compared with the purely excitatory stimulations applied to the steady state, the inhibitory preceding excitatory stimulation to form pairs induces the firing rate increased for type II and III excitabilities instead of type I excitability, when the interval between the inhibitory and excitatory stimulation within each pair is suitable. Secondly, the threshold mechanism for the PIF phenomenon is acquired. For type II and III excitabilities, the inhibitory stimulation induces subthreshold oscillations around the steady state. During the middle and ending phase of the ascending part and the beginning phase of the descending part within a period of the subthreshold oscillations, the threshold to evoke an action potential by an excitatory stimulation becomes weaker, which is the cause for the PIF phenomenon. Last, a theoretical estimation for the range of the interval between the inhibitory and excitatory stimulation for the PIF phenomenon is acquired, which approximates half of the intrinsic period of the subthreshold oscillations for the relatively strong stimulations and becomes narrower for the relatively weak stimulations. The interval for the PIF phenomenon is much shorter for type III excitability, which is closer to the experiment observation, due to the shorter period of the subthreshold oscillations. The results present the excitability and threshold mechanism for the PIF phenomenon, which provide comprehensive and deep explanations to the PIF phenomenon.

Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, 𝛾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.

Gamma oscillation (GAMMA) in the local field potential (LFP) is a synchronized activity commonly found in many brain regions, and it has been thought as a functional signature of network connectivity in the brain, which plays important roles in information processing. Studies have shown that the response property of GAMMA is related to neural interaction through local recurrent connections (RC), feed-forward (FF), and feedback (FB) connections. However, the relationship between GAMMA and long-range horizontal connections (HC) in the brain remains unclear. Here, we aimed to understand this question in a large-scale network model for the primary visual cortex (V1). We created a computational model composed of multiple excitatory and inhibitory units with biologically plausible connectivity patterns for RC, FF, FB, and HC in V1; then, we quantitated GAMMA in network models at different strength levels of HC and other connection types. Surprisingly, we found that HC and FB, the two types of large-scale connections, play very different roles in generating and modulating GAMMA. While both FB and HC modulate a fast gamma oscillation (around 50-60 Hz) generated by FF and RC, HC generates a new GAMMA oscillating around 30 Hz, whose power and peak frequency can also be modulated by FB. Furthermore, response properties of the two GAMMAs in a network with both HC and FB are different in a way that is highly consistent with a recent experimental finding for distinct GAMMAs in macaque V1. The results suggest that distinct GAMMAs are signatures for neural connections in different spatial scales and they might be related to different functions for information integration. Our study, for the first time, pinpoints the underlying circuits for distinct GAMMAs in a mechanistic model for macaque V1, which might provide a new framework to study multiple gamma oscillations in other cortical regions.

Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different regional characteristics. Sociocultural and regulatory aspects, as well as health policies, play a central role in addition to medical care and prescription practices. The users mainly display self-involved motivations related to cognitive enhancement, emotional stability, and adaptivity. Natural stimulants, as well as drugs, represent substance abuse groups. The latter comprise purines, methylxanthines, phenylethylamines, modafinil, nootropics, antidepressants but also benzodiazepines, β-adrenoceptor antagonists, and cannabis. Predominant pharmacodynamic target structures of these substances are the noradrenergic/dopaminergic and cholinergic receptor/transporter systems. Further targets comprise adenosine, serotonin, and glutamate receptors. Meta-analyses of randomized-controlled studies in healthy individuals show no or very limited verifiability of positive effects of pNE on attention, vigilance, learning, and memory. Only some members of the substance abuse groups, i.e., phenylethylamines and modafinil, display positive effects on attention and vigilance that are comparable to caffeinated drinks. However, the development of new antidementia drugs will increase the availability and the potential abuse of pNE. Social education, restrictive regulatory measures, and consistent medical prescription practices are essential to restrict the phenomenon of neuroenhancement with its social, medical, and ethical implications. This review provides a comprehensive overview of the highly dynamic field of pharmacological neuroenhancement and elaborates the dramatic challenges for the medical, sociocultural, and ethical fundaments of society.