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.

Background A growing body of evidence suggests that both auricular acupuncture and transcutaneous auricular vagus nerve stimulation (taVNS) can induce antinociception and relieve symptoms of migraine. However, their instant effects and central treatment mechanism remain unclear. Many studies proved that the amygdalae play a vital role not only in emotion modulation but also in pain processing. In this study, we investigated the modulation effects of continuous taVNS at acupoints on the FC of the bilateral amygdalae in MwoA. Methods Thirty episodic migraineurs were recruited for the single-blind, crossover functional magnetic resonance imaging (fMRI) study. Each participant attended two kinds of eight-minute stimulations, taVNS and sham-taVNS (staVNS), separated by seven days in random order. Finally, 27 of them were included in the analysis of seed-to-voxel FC with the left/right amygdala as seeds. Results Compared with staVNS, the FC decreased during taVNS between the left amygdala and left middle frontal gyrus (MFG), left dorsolateral superior frontal gyrus, right supplementary motor area (SMA), bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus, so did the FC of the right amygdala and left MFG. A significant positive correlation was observed between the FC of the left amygdala and right SMA and the frequency/total time of migraine attacks during the preceding four weeks. Conclusion Continuous taVNS at acupoints can modulate the FC between the bilateral amygdalae and pain-related brain regions in MwoA, involving the limbic system, default mode network, and pain matrix, with obvious differences between the left amygdala and the right amygdala. The taVNS may produce treatment effects by modulating the abnormal FC of the amygdala and pain networks, possibly having the same central mechanism as auricular acupuncture.

Background. Poststroke cognitive impairment (PSCI) is a common cause of disability among patients with stroke. Meanwhile, acupuncture has increasingly been used to improve motor and cognitive function for stroke patients. The aim of the present study was to summarize and evaluate the evidence on the effectiveness of acupuncture in treating PSCI. Methods. Eight databases (PubMed, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, Medline, Embase databases) were searched from January 2010 to January 2020. Meta-analyses were conducted for the eligible randomized controlled trials (RCTs). Assessments were performed using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Barthel Index (BI), or modified Barthel Index (MBI). Results. A total of 657 relevant RCTs were identified, and 22 RCTs with 1856 patients were eventually included. Meta-analysis showed that acupuncture appeared to be effective for improving cognitive function as assessed by MMSE ( mean difference MD = 1.73 , 95% confidence interval (CI) (1.39, 2.06), P < 0.00001 ) and MoCA ( MD = 2.32 , 95% CI (1.92, 2.73), P < 0.00001 ). Furthermore, it also suggested that acupuncture could improve the activities of daily life (ADL) for PSCI patients as assessed by BI or MBI ( SMD = 0.97 , 95% CI (0.57, 1.38), P < 0.00001 ). Conclusions. Compared with nonacupuncture group, acupuncture group showed better effects in improving the scores of MMSE, MoCA, BI, and MBI. This meta-analysis provided positive evidence that acupuncture may be effective in improving cognitive function and activities of daily life for PSCI patients. Meanwhile, long retention time of acupuncture may improve cognitive function and activities of daily life, and twist technique may be an important factor that could influence cognitive function. However, further studies using large samples and a rigorous study design are needed to confirm the role of acupuncture in the treatment of PSCI.

In this paper, we show some dynamical and biological mechanisms of the short-term memory (the fixed point attractor) through the toggle switch in the FitzHugh-Nagumo model (FN). Firstly, we obtain the bistable conditions, show the effect of Gaussian noise on the toggle switch, and explain the short-term memory's switch mechanism by mean first passage time (MFPT). Then, we obtain a Fokker-Planck equation and illustrate the meaning of the monostable and bistable state in the short-term memory. Furthermore, we study the toggle switch under the interaction of network and noise. Meanwhile, we show that network structure and noise play a vital role in the toggle switch based on network mean first passage time (NMFPT). And we illustrate that the modest clustering coefficient and noise are necessary to maintain memories. Finally, the numerical simulation shows that the analytical results agree with it.

Peripheral nerve networks (PNNs) play a vital role in the neural recovery after spinal cord injury (SCI). Electroacupuncture (EA), as an alternative medicine, has been widely used in SCI and was proven to be effective on neural functional recovery. In this study, the interaction between PNNs and semaphrin3A (Sema3A) in the recovery of the motor function after SCI was observed, and the effect of EA on them was evaluated. After the establishment of the SCI animal model, we found that motor neurons in the ventral horn of the injured spinal cord segment decreased, Nissl bodies were blurry, and PNNs and Sema3A as well as its receptor neuropilin1 (NRP1) aggregated around the central tube of the gray matter of the spinal cord. When we knocked down the expression of Sema3A at the damage site, NRP1 also downregulated, importantly, PNNs concentration decreased, and tenascin-R (TN-R) and aggrecan were also reduced, while the Basso-Beattie-Bresnahan (BBB) motor function score dramatically increased. In addition, when conducting EA stimulation on Jiaji (EX-B2) acupoints, the highly upregulated Sema3A and NRP1 were reversed post-SCI, which can lessen the accumulation of PNNs around the central tube of the spinal cord gray matter, and simultaneously promote the recovery of motor function in rats. These results suggest that EA may further affect the plasticity of PNNs by regulating the Sema3A signal and promoting the recovery of the motor function post-SCI.

Purpose. The study was aimed at elucidating the molecular mechanism underlying neuropathic pain induced by spared nerve injury (SNI). Methods. The microarray data of GSE30691 were downloaded from the Gene Expression Omnibus database, including sciatic nerve lesion samples at 3, 7, 21, and 40 days after SNI and sham control samples at 3, 7, and 21 days. Differential analysis along with Mfuzz clustering analysis was performed to screen crucial clusters and cluster genes. Subsequently, comprehensive bioinformatic analyses were performed, including functional enrichment analysis, protein-protein interaction (PPI) network and module analysis, and transcription factor- (TF-) gene and miRNA-target interaction predictions. Moreover, the screened differentially expressed genes (DEGs) were corroborated using two other microarray datasets. Results. Three clusters with different change trends over time after SNI were obtained. Protein kinase CAMP-activated catalytic subunit beta (Prkacb), complement C3 (C3), and activating transcription factor 3 (Atf3) were hub nodes in the PPI network, and fibroblast growth factor 9 (Fgf9) was found to interact with more TFs. Prkacb and Fgf9 were significantly enriched in the MAPK signaling pathway. Moreover, rno-miR-3583-5p was targeted by Fgf9, and rno-miR-1912-3p was targeted by neuregulin 1 (Nrg1). Key genes like Nrg1 and Fgf9 in cluster 1, Timp1 in cluster 2, and Atf3 and C3 in cluster 3 were screened out after corroborating microarray data with other microarray data. Conclusions. Key pathways like the MAPK signaling pathway and crucial genes like Prkacb, Nrg1, Fgf9, Timp1, C3, and Atf3 may contribute to SNI-induced neuropathic pain development in rats.

A model is introduced by coupling two three-dimensional Hindmarsh-Rose models with the help of a nonsmooth memristor. The firing patterns dependent on the external forcing current are explored, which undergo a process from adding-period to chaos. The stability of equilibrium points of the considered model is investigated via qualitative analysis, from which it can be gained that the model has diversity in the number and stability of equilibrium points for different coupling coefficients. The coexistence of multiple firing patterns relative to initial values is revealed, which means that the referred model can appear various firing patterns with the change of the initial value. Multiple firing patterns of the addressed neuron model induced by different scales are uncovered, which suggests that the discussed model has a multiscale effect for the nonzero initial value.

Hair cells (HCs) in the mammalian cochleae cannot spontaneously regenerate once damaged, resulting in permanent hearing loss. It has been shown that Atoh1 overexpression induces hair cell-like cells (HCLCs) in the cochlea of newborn rodents, but this is hard to achieve in adult mammals. In this study, we used a three-dimensional cochlear culture system and an adenoviral-mediated delivery vector to overexpress Atoh1 in adult mouse cochleae. HCLCs were successfully induced from 3 days after virus infection (3 DVI) in vitro, and the number increased with time. HCLCs were myosin7a positive and distinguishable from remnant HCs in a culture environment. Meanwhile, patch-clamp results showed that noninactive outward potassium currents (sustained outward potassium currents) could be recorded in HCLCs and that their magnitude increased with time, similar to normal HCs. Furthermore, transient HCN currents were recorded in some HCLCs, indicating that the HCLCs experienced a developmental stage similar to normal HCs. We also compared the electrophysiological features of HCLCs from adult mice with native HCs and found the HCLCs gradually matured, similar to the normal HCs. Meanwhile, HCLCs from adult mice possessed the same bundles as developmental HCs. However, these HCLCs did not express prestin, which is a special marker for outer hair cells (OHCs), even at 13 DVI. These results demonstrate that Atoh1 overexpression induces HCLC formation in the adult mammalian cochlea and that these HCLCs were functional and experienced a developmental process similar to that of normal HCs.

Previous research has demonstrated that serum lipid profile is associated with cognitive function as well as brain structure and function in middle-aged, elderly, and clinical populations. However, the nature and extent of lipids-brain-cognition relationships in young adulthood are largely unknown. In this study, 157 healthy young adults underwent resting-state functional MRI scans. Functional connectivity between and within 14 functional networks were calculated using independent component analysis. Peripheral venous blood samples were collected to measure serum lipids. Working memory was assessed using a 3-back task. Linear regression, correlation, and mediation analyses were conducted to test for potential associations between serum lipids, inter- and intranetwork functional connectivity, and working memory performance. We found that higher serum triglyceride (TG) level was correlated with stronger connectivity between left frontoparietal and ventral attention networks, between right frontoparietal and dorsal attention networks, between right frontoparietal and dorsal sensorimotor networks, between right frontoparietal and lateral visual networks, and between salience (SN) and ventral sensorimotor (vSMN) networks, as well as lower connectivity between posterior default mode and left frontoparietal networks, between left frontoparietal and medial visual networks, and between ventral attention and dorsal sensorimotor networks. In addition, higher SN-vSMN connectivity was related to lower 3-back accuracy. More importantly, the relationship between serum TG and 3-back accuracy was mediated by SN-vSMN connectivity. Our findings not only may expand existing knowledge regarding serum lipids-brain-cognition relations from the perspective of large-scale functional network organization but also may inform a translational conceptualization of how to improve cognitive function through regulating serum lipids.

It is generally believed that the placebo response can elicit an analgesic effect, whilst the nocebo response can elicit a hyperalgesia effect in pain. Placebo analgesia and nocebo hyperalgesia effects are increasing concerns for researchers. Growing evidence suggests personality differences have an impact on both placebo and nocebo effects. However, previous studies have not reached a unified conclusion. We designed this study to explore the personality differences of functional magnetic resonance imaging (fMRI) signals in placebo response and nocebo response by using psychophysiological interaction (PPI) analysis. 30 healthy subjects underwent conditioning induction training to establish expectations of placebo effect and nocebo effect, and then, all subjects completed the following experimental procedures: (1) baseline scanning, (2) acute pain model establishment, (3) pain status scanning, and (4) pseudorandom scanning of block design of placebo response or nocebo response. Behavioral data were collected after each scan. The results of this study showed that (1) there were significant differences of VAS placebo intervention between the extrovert group and the introvert group (p = 0.004); (2) there were significant differences of VAS nocebo intervention between the extrovert group and the introvert group (p = 0.011); (3) there were significant differences between the VAS placebo intervention and VAS pain status (baseline) in both the extrovert group (p < 0.001) and the introvert group (p = 0.001); (4) there were significant differences between the VAS nocebo intervention and VAS pain status (baseline) in both the extrovert group (p = 0.008) and the introvert group (p < 0.001). Moreover, there were significant differences in the brain network for placebo and nocebo responses between different personalities. We found that (1) deactivation differences of the pain-related network and limbic system play an important role in personality differences associated with placebo analgesia and (2) differences of control of anxiety and activation of dorsolateral prefrontal cortex may cause the personality differences observed in nocebo hyperalgesia.