With the widespread use of electrical equipment, cognitive functions such as working memory (WM) could be severely affected when people are exposed to 50 Hz electromagnetic fields (EMF) for long term. However, the effects of EMF exposure on WM and its neural mechanism remain unclear. In the present paper, 15 rats were randomly assigned to three groups, and exposed to an EMF environment at 50 Hz and 2 mT for a different duration: 0 days (control group), 24 days (experimental group I), and 48 days (experimental group II). Then, their WM function was assessed by the T-maze task. Besides, their local field potential (LFP) in the media prefrontal cortex (mPFC) was recorded by the in vivo multichannel electrophysiological recording system to study the power spectral density (PSD) of θ and γ oscillations and the phase-amplitude coupling (PAC) intensity of θ-γ oscillations during the T-maze task. The results showed that the PSD of θ and γ oscillations decreased in experimental groups I and II, and the PAC intensity between θ and high-frequency γ (hγ) decreased significantly compared to the control group. The number of days needed to meet the task criterion was more in experimental groups I and II than that of control group. The results indicate that long-term exposure to EMF could impair WM function. The possible reason may be the impaired communication between different rhythmic oscillations caused by a decrease in θ-hγ PAC intensity. This paper demonstrates the negative effects of EMF on WM and reveals the potential neural mechanisms from the changes of PAC intensity, which provides important support for further investigation of the biological effects of EMF and its mechanisms.
Humans ; Rats ; Animals ; Memory, Short-Term/physiology* ; Electromagnetic Fields/adverse effects* ; Prefrontal Cortex ; Cognition

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, with the predominant clinical diagnosis of spatial working memory (SWM) deficiency, which seriously affects the physical and mental health of patients. However, the current pharmacological therapies have unsatisfactory cure rates and other problems, so non-pharmacological physical therapies have gradually received widespread attention. Recently, a novel treatment using 40 Hz light flicker stimulation (40 Hz-LFS) to rescue the cognitive function of model animals with AD has made initial progress, but the neurophysiological mechanism remains unclear. Therefore, this paper will explore the potential neural mechanisms underlying the modulation of SWM by 40 Hz-LFS based on cross-frequency coupling (CFC). Ten adult Wistar rats were first subjected to acute LFS at frequencies of 20, 40, and 60 Hz. The entrainment effect of LFS with different frequency on neural oscillations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was analyzed. The results showed that acute 40 Hz-LFS was able to develop strong entrainment and significantly modulate the oscillation power of the low-frequency gamma (lγ) rhythms. The rats were then randomly divided into experimental and control groups of 5 rats each for a long-term 40 Hz-LFS (7 d). Their SWM function was assessed by a T-maze task, and the CFC changes in the HPC-mPFC circuit were analyzed by phase-amplitude coupling (PAC). The results showed that the behavioral performance of the experimental group was improved and the PAC of θ-lγ rhythm was enhanced, and the difference was statistically significant. The results of this paper suggested that the long-term 40 Hz-LFS effectively improved SWM function in rats, which may be attributed to its enhanced communication of different rhythmic oscillations in the relevant neural circuits. It is expected that the study in this paper will build a foundation for further research on the mechanism of 40 Hz-LFS to improve cognitive function and promote its clinical application in the future.
Humans ; Adult ; Rats ; Animals ; Memory, Short-Term/physiology* ; Rats, Wistar ; Neurodegenerative Diseases ; Hippocampus ; Prefrontal Cortex

Working memory is an important foundation for advanced cognitive function. The paper combines the spatiotemporal advantages of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to explore the neurovascular coupling mechanism of working memory. In the data analysis, the convolution matrix of time series of different trials in EEG data and hemodynamic response function (HRF) and the blood oxygen change matrix of fNIRS are extracted as the coupling characteristics. Then, canonical correlation analysis (CCA) is used to calculate the cross correlation between the two modal features. The results show that CCA algorithm can extract the similar change trend of related components between trials, and fNIRS activation of frontal pole region and dorsolateral prefrontal lobe are correlated with the delta, theta, and alpha rhythms of EEG data. This study reveals the mechanism of neurovascular coupling of working memory, and provides a new method for fusion of EEG data and fNIRS data.
Electroencephalography/methods* ; Memory, Short-Term ; Neurovascular Coupling/physiology* ; Prefrontal Cortex ; Spectroscopy, Near-Infrared/methods*

Increasing studies have provided cognitive and neuron evidence for not only the similarities, but also the differences between physical pain and social pain in the brain basis. Comparing the similarities and differences of the brain basis of physical pain and social pain helps us to clarify the mechanism of the occurrence and change of pain, and provide theoretical evidence for clinical pain treatment. In this review, we summarized studies to delineate the brain mechanisms of physical pain and social pain. Through the review of existing studies, we found that both physical pain and social pain can invoke the same brain regions that process emotional experience (the dorsal anterior cingulate cortex, anterior insula), emotion regulation (lateral prefrontal cortex) and somatosensory (the posterior insula, secondary sensory cortex). However, the voxel-level activated patterns of physical and social pain differ in the same brain region (dorsal anterior cingulate gyrus, dorsolateral prefrontal cortex, etc.), and the overlapping brain regions (for example, ventrolateral prefrontal cortex) have varied effect on these two types of pain. In addition, studies have shown that the brain activation pattern for social pain may be influenced by the experimental paradigm. Future studies should actively adopt a data-driven way to examine the brain basis of physical pain and social pain, especially the nerve activation mode, aiming to consummate the theory of pain.
Brain ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Pain/psychology* ; Prefrontal Cortex/physiology*

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.
Animals ; Glutamic Acid ; physiology ; Male ; Mental Recall ; physiology ; Mice, Inbred C57BL ; Neural Pathways ; cytology ; physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons ; physiology ; Prefrontal Cortex ; cytology ; physiology ; Spatial Memory ; physiology ; Temporal Lobe ; cytology ; physiology

Working memory (WM) refers to the process of temporally maintaining and manipulating input information. WM is the global workspace of cognitive functions, however, with severely restricted capacity and precision. Previous cognitive and computational models discussed the methods of calculating capacity and precision of WM and the reason why they are so limited. It still remains debated which model is the best across all datasets, and whether there exists upper limits of items. Besides, sensory cortices and the frontal-parietal loop are suggested to represent WM memorandum. Yet recently, the sensory recruitment hypothesis that posits an important role of sensory cortices in WM is strongly argued. Meanwhile, whether the prefrontal cortex shows sustained activity or bursting γ oscillations is intensely debated as well. In the future, disentangling the contribution to WM of feedforward γ vs feedback α/β oscillations, and/or dopamine vs serotonin systems, is critical for understanding the neural mechanisms underlying WM. It will further do help to recognize the basis for the psychiatric (e.g. schizophrenia) or neurological (e.g. Alzheimer's disease) disorders, and potentially to develop effective training and intervening methods.
Cognition ; Humans ; Memory, Short-Term ; Models, Neurological ; Parietal Lobe ; physiology ; Prefrontal Cortex ; physiology

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia, where two different contexts (dark and bright) were matched with a high (52°C) or low (48°C) temperature in the hot-plate test during training. Before and after training, we set the temperature to the high level in both contexts. Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone (an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.
Action Potentials ; drug effects ; physiology ; Analgesics ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Electric Stimulation ; Female ; In Vitro Techniques ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Optogenetics ; Pain ; drug therapy ; pathology ; physiopathology ; Pain Measurement ; drug effects ; Pain Threshold ; drug effects ; physiology ; Patch-Clamp Techniques ; Physical Stimulation ; Prefrontal Cortex ; drug effects ; metabolism ; pathology ; Pyramidal Cells ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Time Factors

The dorsolateral prefrontal cortex (DLPFC) is considered to play a crucial role in many high-level functions, such as cognitive control and emotional regulation. Many studies have reported that the DLPFC can be activated during the processing of emotional information in tasks requiring working memory. However, it is still not clear whether modulating the activity of the DLPFC influences emotional perception in a detection task. In the present study, using transcranial direct-current stimulation (tDCS), we investigated (1) whether modulating the right DLPFC influences emotional face processing in a detection task, and (2) whether the DLPFC plays equal roles in processing positive and negative emotional faces. The results showed that anodal tDCS over the right DLPFC specifically facilitated the perception of positive faces, but did not influence the processing of negative faces. In addition, anodal tDCS over the right primary visual cortex enhanced performance in the detection task regardless of emotional valence. Our findings suggest, for the first time, that modulating the right DLPFC influences emotional face perception, especially faces showing positive emotion.
Adult ; Emotions ; Facial Recognition ; physiology ; Female ; Humans ; Male ; Neuropsychological Tests ; Prefrontal Cortex ; physiology ; Social Perception ; Transcranial Direct Current Stimulation ; Young Adult

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
Animals ; Cyproheptadine ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Membrane Potentials ; drug effects ; physiology ; Mice, Inbred C57BL ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Prefrontal Cortex ; drug effects ; physiology ; Pyramidal Cells ; drug effects ; physiology ; Receptors, sigma ; agonists ; metabolism ; Tetraethylammonium ; pharmacology ; Tissue Culture Techniques

Behavioral adjustment plays an important role in the treatment and relapse of drug addiction. Nonetheless, few studies have examined behavioral adjustment and its plasticity following error commission in methamphetamine (METH) dependence, which is detrimental to human health. Thus, we investigated the behavioral adjustment performance following error commission in long-term METH addicts and how it varied with the application of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty-nine male long-term METH addicts (for > 3 years) were randomly assigned to high-frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two-choice oddball task. Twenty-six age-matched, healthy male adults participated in the two-choice oddball task pretest to establish normal performance for comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly decreased the post-error slowing effect in response times of METH addicts. In addition, the 10 Hz rTMS intervention remarkably reduced the reaction times during post-error trials but not post-correct trials. While the 10 Hz rTMS group showed a more pronounced post-error slowing effect than the healthy participants during the pretest, the post-error slowing effect in the posttest of this sample was similar to that in the healthy participants. These results suggest that high-frequency rTMS over the left DLPFC is a useful protocol for the improvement of behavioral adjustment after error commission in long-term METH addicts.
Adjustment Disorders ; etiology ; therapy ; Adult ; Amphetamine-Related Disorders ; complications ; therapy ; Case-Control Studies ; Central Nervous System Stimulants ; adverse effects ; Choice Behavior ; physiology ; Functional Laterality ; Humans ; Male ; Methamphetamine ; adverse effects ; Middle Aged ; Prefrontal Cortex ; physiology ; Reaction Time ; physiology ; Transcranial Magnetic Stimulation ; methods ; Young Adult