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Abstract:Neural oscillation is a rhythmic pattern of neural activity in the central nervous system, which has been found to be closely related to abnormal neural oscillations in psychoneurological disorders. Exogenous rhythmic stimulation can effectively modulate abnormal neural oscillations through entrainment and neuroplasticity, which has the potential to treat psychoneurological disorders. Currently, the main exogenous rhythmic brain stimulation techniques include transcranial alternating current stimulation (tACS), temporal interference (TI) stimulation and rhythmic sensory stimulation. We describe the effects of tACS and TI from the perspective of different frequency bands, and rhythmic sensory stimulation from the perspective of visual, acoustic, and synergistic stimulation patterns. This paper reviews the principles of exogenous rhythmic brain stimulation techniques, as well as the current intervention strategies and the progress of treatment effects of different techniques in the clinical treatment of neuropsychiatric disorders. The use of rhythmic stimulation for the treatment of clinical symptoms in patients with psychoneurological disorders is still in the exploratory stage and needs to be validated in larger samples for safety and long-term efficacy. Simultaneously, further studies that explore the exact mechanisms of such techniques are essential to optimize the design of the rhythmic modulation strategies so as to gain stronger positive effects. Additionally, clinical trials that analyze the effects of synergistic treatment with drugs and the design of portable home devices will be beneficial for patients.

Abstract:Alzheimer’s disease (AD) is a degenerative disorder of the central nervous system in the elderly and the pre-aging period, whose main clinical manifestation is progressive cognitive impairment. Till now, no treatment for AD has been found effective and the drugs can only delay the progression of the disease with limited efficacy, and often accompanied by side effects. In recent years, neuromodulation, as a method of targeting stimulation to regulate the activity of target brain regions, has gained much attention. It has been widely used in the treatment and research of AD. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) modulate cortical neuronal activity and excitability by changing neuronal membrane potential. Clinical studies have shown that these two non-invasive methods can improve cognitive impairment in AD patients to a certain extent. However, due to the low spatial accuracy and various effect sizes, the optimal stimulation target area, parameters and modes of these two methods have not been unified yet. Deep brain stimulation (DBS) can improve cognitive function in AD patients by regulating cognition-related neural circuits and optogenetics stimulation precisely regulates the activity of specific neurons and neural circuits through genetic and optical means. The research results of cognitive function related circuits and specific neurons by the two innovative methods provide a theoretical basis for identifying the injury mechanism of AD cognitive impairment and the therapeutic targets at the level of brain functional network. This paper reviews the application and research status of the above mentioned four typical neuromodulation methods from the aspects of effect, mechanism, stimulation of brain area and stimulation parameters, so as to provide new ideas for the application of neuromodulation in clinical treatment of AD in the future.

Abstract:Alzheimer’s disease (AD) is a common central neurodegenerative disease characterized by progressive cognitive impairment and memory loss. It has become one of the most serious problems in geriatric medicine with a large number of incidences and a wide range of effects. Clinical drug treatment of AD has limited effects, and there are certain limitations and side effects. At present, the treatment methods of chemical and physical intervention for AD are gradually attracting people’s attention. Olfactory intervention stimulated by odor or electrode can enhance excitability and synaptic transmission of olfactory neurons. Therapy of photobiomodulation can raise cerebral blood flow, promote nerve excitation and neuronal plasticity. Photothermal therapy can be used to decompose of Aβ aggregates. γ oscillations induced by 40 Hz audiovisual stimulation is mainly targeted to decrease amyloid plaques. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) regulate neuronal activity and excitability in the brain by directly inducing action potentials and increasing the resting membrane potential of cortical neurons, respectively. Transcranial alternating current stimulation (tACS) modulates cognitive function through entrainment and resonance effects that bring large populations of neurons into local oscillating networks. Exposure to a thermoneutral environment can reduce insoluble Aβ while repeated short-term cold exposure at 4℃ can block hypothermia-induced Tau hyperphosphorylation. Studies have shown that chemical and physical intervention such as olfactory intervention, light therapy, electrical brain stimulation, acoustic and optical stimulation, temperature intervention can improve metabolism by improving neurogenesis, neuroprotection, neuronal excitability, neuronal plasticity, cerebral blood flow, reducing Aβ deposition and Tau hyperphosphorylation to improve AD symptoms and cognitive function. This article reviews the mechanism and efficacy of different physical interventions on AD, so as to provide a theoretical basis for the implementation of physical interventions to prevent and delay AD.

Abstract:Alzheimer’s disease (AD) is a neurodegenerative disease that causes central neuropathy. The close association between bone and brain reveals an intrinsic link between bone and AD. Bone is gaining attention as a bone endocrine organ, which secretes osteogenic factors (SOST, OCN, OPN), and generates microglia and bone marrow stem cells. These Factors and cells derived from bone cross the blood-brain barrier and regulate the physiological properties of the brain, so then improve the metabolic process of AD. Exercise regulates skeletal endocrine function, increases the secretion and expression of bone-derived factors, and ultimately delays AD pathological changes and improves the level of AD cognitive function. This paper focuses on the ameliorative effects of bone-derived factors on AD, and new approaches and perspectives on exercise stimulation of skeletal secretion to improve the AD process, providing new ideas for brain-bone interaction studies.

Abstract:Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The pathological changes of AD include synaptic dysfunction, neurotransmitter imbalance, neuroinflammation, deposition plaques with β Amyloid (Aβ) protein as the core in different regions of the brain, and abnormal accumulation of Tau proteins in nerve cells which form neuronal fiber tangles. If Aβ, Tau, and damaged organelles in nerve cells can’t be degraded and cleared in time, it will produce significant neurotoxicity and cause neuronal damage, leading to AD. The degradation of Aβ proteins and damaged organelles depends on the autophagy-lysosome pathway. When the degradation function of neuronal cells is abnormal, neurons are prone to accumulate abnormal proteins and damaged organelles which lead to neuronal damages. Therefore, the decrease in autophagy lysosome function and the impaired degradation of neurotoxic substances play an important role in the development of AD. Abnormal autophagy function leads to the aggregation of Aβ and Tau in neurons, leading to strong neurotoxicity and the occurrence of AD symptoms. Decrease in the number of lysosomes, abnormal lysosomal pH and decreased activities of lysosomal enzymes will lead to damage of the autophagy-lysosomal system which leads to an increase in abnormal protein aggregation and triggers AD. Exercise is the most effective non-pharmacological intervention to slow down cognitive decline in dementia patients. Exercise can quickly and safely activate the autophagy lysosomal system, improve the clearance efficiency of abnormal proteins in the central and peripheral tissues, and thereby alleviate cognitive and memory impairment in AD patients. Firstly, exercises can activate the Phosphatidylinositol 3-kinases/protein kinase B (PI3K/Akt) pathway, which will further decreased the activation of glycogen synthase kinase-3β(GSK-3β) and reverse the abnormal function of mammalian target of rapamycin (mTOR). Through this pathway, exercises will improve autophagy activity, promote the degradation and clearance of Aβ and hyperphosphorylated Tau, and alleviate AD cognitive dysfunction. In addition, exercise can also regulate the Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway through an adiponectin receptor 1(AdipoR1) dependent or independent ways to enhance cell autophagy, increase the number of autolysosomes in cells, enhance lysosomal function, and improve cognition. As an effective TFEB activator, exercise can upregulate related signaling pathways by activating TFEB to promote the expression of autophagy and lysosomal genes, improve clearance efficiency of toxic proteins and damaged organelles, and reduce Aβ deposition and neuronal apoptosis to improve cognitive impairment in AD patients. Autophagy lysosomes may be a new target for treating neurodegenerative diseases such as AD which is caused by the accumulation of abnormal proteins and damaged organelles. Exercise can activate autophagy-lysosomes pathway to prevent and delay the progression of AD. This article elaborated the role of autophagy lysosome dysfunction in the occurrence and development of AD, laid out the underlying mechanism of exercise preventing Alzheimer’s disease by regulating autophagy-lysosome pathway. This review aims to provide a new strategy for the prevention and treatment of AD.

Abstract:Alzheimer’s disease (AD) is a neurodegenerative disease, and drug therapy is currently the main strategy for AD treatment, but it only has a delaying or alleviating effect. This article aims to review the effects of various sensory stimulation and multisensory stimulation on AD, and explain possible mechanisms to provide new ideas for further research. The results show that light stimulation therapy mainly improves the sleep-wake cycle of AD patients, thereby improving their agitation and restlessness. However, some studies have shown only statistical improvement without significant clinical implications. This may be due to different stages of AD in the subjects studied. Light therapy has a more significant effect on early-stage AD patients, so light therapy can be used to improve their sleep and mood. However, light therapy may also exacerbate circadian rhythm disturbances in AD patients, and its effectiveness is influenced by seasonality, with daytime light intensity affecting its efficacy. Olfactory stimulation therapy is a safe and effective treatment for AD, mainly used to improve memory in AD patients. This is mainly because olfactory stimulation can stimulate neurons between the olfactory bulb and the limbic system, and activate the amygdala-hippocampus complex, olfactory cortex, and temporal lobe, which are physiologically related to memory, thereby improving memory in AD patients. Olfactory stimulation therapy is particularly suitable for severe AD patients, and each AD patient may have a different response to olfactory stimulation, so personalized treatment based on patient preferences and tolerability is needed. Sound stimulation therapy mainly involves music stimulation, which has positive effects on AD patients. It may improve music memory, promote brain plasticity, and improve patients’ mood and cognitive function by regulating the release of chemicals. Music stimulation therapy can improve cognition and mood in patients with AD, and different types of music can have different effects on AD treatment. Therefore, targeted treatment using different music can be adopted in music therapy for AD, and it can be observed that the longer the duration of music therapy, the longer the duration of its effects. Therefore, music therapy can be integrated into the daily lives of AD patients to achieve long-lasting effects. Rhythm stimulation can improve anxiety levels and enhance cognitive abilities in mild to moderate AD patients. Multisensory stimulation mainly includes the design of multisensory activity rooms such as Snoezelen and therapeutic gardens, as well as dynamic and interactive virtual environments created by virtual reality (VR) technology, which integrate the therapeutic effects of single sensory stimulation. However, when using multisensory stimulation, factors such as practical application scenarios and duration need to be carefully considered.

Abstract:Cognitive impairment represents a mental health condition primarily affecting cognitive faculties such as learning, memory, perception, and problem-solving abilities. This condition frequently manifests in patients diagnosed with Alzheimer’s disease, vascular dementia, and mild cognitive impairment. In comparison to pharmaceutical interventions, acupuncture treatment offers distinct advantages, including cost-effectiveness, tolerability, and a strong safety profile, positioning it as a promising approach to enhance cognitive function. Numerous studies have demonstrated the significant impact of acupuncture in ameliorating cognitive deficits among individuals with cognitive impairment. However, the precise mechanisms underlying the cognitive enhancement achieved through acupuncture remain elusive. Building upon the theoretical principles of Chinese medicine, which emphasize the interconnectedness of the brain and the gastrointestinal system, and drawing from contemporary experimental investigations highlighting the intricate relationship between the brain-gut axis and acupuncture’s cognitive benefits, this paper undertakes a comprehensive examination of the mechanisms by which acupuncture may improve cognitive impairment. By elucidating these mechanisms through the lens of the brain-gut axis theory, this review aims to provide a foundational framework for further exploration of innovative acupuncture approaches for the treatment of cognitive impairment. Moreover, the study of the micro-level mechanisms involving gut microbes is propelled by our understanding of the brain-gut axis in cognitive enhancement through acupuncture. Nonetheless, gut microbial communities exhibit distinct characteristics, including individual variations, dynamic fluctuations, and a diverse range of species. Thus, it becomes imperative to investigate, enhance, and standardize novel acupuncture methods that specifically target the regulation of gut homeostasis. In this context, our review encompasses acupuncture and moxibustion interventions designed to address cognitive impairments through the prism of the brain-gut axis. These interventions encompass the preservation of gut microbial ecological equilibrium, the maintenance of gut microbiota diversity, the modulation of beneficial microbial population levels, the regulation of metabolic processes, the promotion of brain-derived neurotrophic factor (BDNF) production, the inhibition of microglial cell activation, the mitigation of neuroinflammatory responses, and the reduction of Aβ protein accumulation.

Abstract:Cognitive function is a crucial aspect of brain functioning, but it can be compromised in various neurological pathologies and diseases, resulting in cognitive deficits. Currently, effective treatments and rehabilitation measures for cognitive impairment patients remain limited. Light treatment, as a non-invasive physical therapy, has emerged as a promising approach and has garnered increasing attention. This article provides an overview of the clinical application status of light treatment in cognitive impairment associated with neurological and psychiatric disorders, with a specific focus on Alzheimer’s Disease (AD), mild cognitive impairment (MCI), post-traumatic cognitive impairment (PTCI), and cognitive impairments linked to schizophrenia (CIAS). The mechanisms of improving effects of light treatment on cognition are multifaceted, including the regulation of circadian rhythms, neuroprotection and repair, enhancement of blood circulation, modulation of neurotransmitters, anti-inflammatory effects, promotion of neuroplasticity, and reduction of oxidative stress. Light treatment is believed to influence brain electrical activity. The inconsistent finding on the effects of 40 Hz light stimulation on cognitive impairment associated with neurodegenerative diseases may be related to the inconsistency between the light treatment paradigm and the animal model. The organic or structural damage of neurons during the middle or late stages of the disease limits the preventive and ameliorative effects of light treatment. Additionally, light treatment can improve cognitive function by affecting the activity of neural circuits. ipRGC-SCN-CA1 and ipRGC-vLGN/IGL-Re-CA1 neural circuits were reported to involved in the cognition-improving effects of light treatment. Several neurotransmitters (acetylcholine, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid), neurotrophic factors (brain-derived neurotrophic factor, nerve growth factor, and vascular endothelial growth factor) and hormones (corticotropin releasing hormone (CRH) and cortisol) also participated in the mechanisms of light treatment. Understanding these underlying mechanisms is crucial for comprehending the beneficial effects of light treatment on cognitive impairment. The article also discusses the limitations of light treatment in clinical applications, including standardizing light parameters and the impact of individual differences. The limitations of light treatment in clinical applications encompass standardized light parameters, individual differences, lack of long-term follow-up data, differences in research designs, and the absence of standardized treatment protocols. Overcoming these limitations requires further research and standardization efforts to ensure the reliability and effectiveness of light treatment in the management of cognitive impairment. This review aims to enhance our understanding of the advancements in light treatment for improving cognitive impairment and elucidate the underlying mechanisms involved. It also provides theoretical support for optimizing parameters and techniques in light treatment for cognitive impairment, thereby promoting its clinical application. Ultimately, this will contribute to further exploration of the potential of light treatment in the management of cognitive impairment associated with neurological and psychiatric disorders and advance related research endeavors.

Abstract:Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment, which seriously endangers the health of patients, and imposes a heavy burden on the patient’s family and society. Therefore, it is of great significance to study its pathogenesis, diagnosis, and treatment. Recently, the research on a therapeutic protocol of 40 Hz light flicker stimulation by regulating the activity of γ rhythmic neural oscillations has made preliminary progress in AD animal models and patients, and it is expected to become an alternative solution for clinical treatment and prevention of AD in the future. And, the therapy has received widespread attention from researchers. This paper presents a 40 Hz light flicker stimulation protocol for AD, and reviews recent reports on improving the cognitive performance of AD animal models and patients, as well as the progress of mechanism research. The 40 Hz light flicker stimulation effectively enhanced the power of γ oscillatory in the visual cortex and cognitively related brain regions such as the hippocampal prefrontal cortex. In the study of cognitive behavior, the 40 Hz light flicker stimulation effectively improved the performance of AD animal models and achieved preliminary satisfactory results in AD patients. The potential mechanism may be that the 40 Hz light flicker stimulation reduces Aβ and tau levels, decreases microglia-mediated inflammatory responses, enhances the expression of genes and proteins, and promotes synaptic transmission and intracellular transport in neurons, resulting in improved pathological characteristics of AD. Meanwhile, the limitations of this protocol are discussed and prospects are made to provide support for the future development of physical therapy for cognitive disorders such as AD.

Abstract:Growing evidence suggests that obesity has negative effects on brain function and structure. Obese individuals exhibit abnormal neural responses in relation to food cues, taste and smell, resting-state activity, and functional connectivity. They also demonstrate impairments in cognitive tasks such as decision-making, inhibitory control, learning and memory, and attention. Bariatric surgery, as a specialized treatment approach, can alter the anatomy and physiological mechanisms of the digestive system, thereby restricting food intake or modifying nutrient absorption to achieve short-term and long-term weight loss effects. It can also improve complications, reduce mortality rates, and enhance quality of life. Recent studies have shown that bariatric surgery has a positive effect on improving obesity-related cognitive dysfunction. This article provides an overview of the association between obesity and cognitive function and focuses on the research progress in recent years regarding the improvement of obesity-related cognitive impairments through bariatric surgery. Several mechanisms may be involved in bariatric surgery to improve obesity-related cognitive dysfunction. Potential mechanisms include weight loss, altered hormone regulation (e.g., ghrelin, leptin), improved insulin sensitivity, reduced systemic inflammation, and changes in gut microbiota. The relationship between bariatric surgery and cognition is complex and multifactorial, and the exact mechanisms are still being explored. Effects of obesity-related complications, hormonal changes, gut-brain-axis, inflammation, brain structure, and nutritional factors on cognitive function after bariatric surgery were discussed. Identifying these mechanisms could help uncover new targets for intervention and provide a basis for optimizing patient outcomes in terms of weight loss and cognitive function.

Abstract:Cerebral ischemia refers to the lack of blood supply in all parts of the brain leading to brain tissue ischemia and hypoxia, which leads to irreversible damage and necrosis of in dense ischemic areas. Its high disability and high mortality rate will cause serious harm to patients and their families. The key to the prognosis of cerebral ischemia is to take some measures to restore blood flow and oxygen supply, control the size of the infarct and save the cells in the penumbra. Hyperbaric oxygen therapy refers to letting patients inhale 100% oxygen under the environmental pressure higher than one atmosphere absolute to increase the oxygen content in the body. It can provide enough oxygen for ischemic hypoxic brain tissue and prevent the further aggravation of injury. Clinical trials have demonstrated that hyperbaric oxygen therapy can improve motor, sensory and cognitive dysfunction in patients with cerebral ischemia and can also be used as an adjuvant therapy. The mechanisms of hyperbaric oxygen therapy in the treatment of cerebral ischemia mainly include increasing the oxygen content, inducing neuroplasticity, regulating cerebral blood flow, regulating the expression level of cytokines, and reducing oxidative stress. It is worth noting that there are some prominent problems in the current research, such as adverse reactions during treatment, uncertainty of the effective therapeutic time window, a certain degree of difference between the results of basic research and clinical research, and the unportability of hyperbaric oxygen chamber. These problems severely limit the clinical application of hyperbaric oxygen therapy. In the future more basic and clinical research are needed to develop a more secure and reliable hyperbaric oxygen therapy protocol, reduce the toxic side effects and adverse reactions that may occur during the treatment, and provide new ideas for the treatment and prognosis of patients with cerebral ischemia

Abstract:Neuropathic pain (NP) is caused by lesion or disease of peripheral or central somatosensory system, accompanied by a certain degree of functional loss and cognitive impairment. Pharmacological treatment makes vital contributions to analgesia, but excessive pharmacological treatment often causes serious side effects, or only provides partial pain relief at tolerable doses. Cognitive-behavioral therapy (CBT) and virtual reality (VR) intervention, as new, non-invasive and safer alternative treatment methods for pain, alleviate neuropathic pain by diverting attention, altering neuroplasticity and neural circuits, and regulating the expression of proinflammatory and anti-inflammatory cytokines. This article analyzed the underlying pathogenesis of neuropathic pain, as well as the analgesic effects and mechanisms of CBT and VR therapy, so as to provide important theoretical guidance for the treatment and intervention of neuropathic pain.

Abstract:Pain is an unpleasant sensory and experience associated with, or resembling that associated with, actual emotional or potential tissue damage. Chronic pain is pain that persists for more than 3 months. Chronic pain is caused by a variety of conditions with high incidence. However, the use of medication to treat chronic pain has certain limitations. Non-opioid medications have limited efficacy for some types of chronic pain, such as neuropathic pain. However, opioid analgesics have limitations due to addiction and gastrointestinal side effects, so non-drug intervention therapy has gradually gained attention. Currently, common non-pharmacological interventions for chronic pain include pulsed radiofrequency (PRF), spinal cord stimulation (SCS), photobiomodulation (PBM) and repetitive transcranial magnetic stimulation (rTMS). PRF is a technique using a low temperature and pulse of electromagnetic radiation to disrupt nerve signaling without denaturing the fibers. PRF therapy involves the insertion of a radiofrequency needle around the target nerve under computer tomography (CT) guidance. The RF generator emits a pulsed current to the needle tip, forming a magnetic field near the target nerve tissue and exerting a neuromodulatory role. Compared with traditional thermocoagulation, the temperature of PRF does not exceed 42°C and finally exerts an analgesic effect without damaging the nerve. Recent studies reveal that analgesic mechanisms of PRF involve downregulations of functions of voltage-gated sodium and calcium channels and ionotropic purinergic receptors (Nav_1.7, Cav_2.2, and P2X3), reduction of the releases of neuropeptides (calcitonin gene-related peptide (CGRP) and substance P (SP)), neurotransmitters (glutamate) and pro-inflammatory mediators (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), and suppression of intracellular signal pathways (ERK/MAPK and p38MAPK). SCS modulates the releases and functions of neurotransmitters by downregulating excitatory glutamate systems and upregulating inhibitory gamma-aminobutyric acid (GABA), endogenous opioids, and the endocannabinoid system. SCS is a therapeutic method that effectively alleviates chronic pain by electrically stimulating the spinal nerves. This procedure involves the implantation of electrodes into the epidural space under local anesthesia, with precise targeting of specific segments of the spinal cord. By delivering pulsed electrical currents, the spinal nerves can be selectively stimulated, effectively blocking the transmission of pain signals and providing much-needed relief from chronic pain. SCS suppresses neuroinflammation, including downregulating glial activation, decreasing releases of pro-inflammatory mediators (colony stimulating factor-1 (CSF-1), resolvin D1 (RVD1), TNF-α and IL-1β), and regulating p38MAPK signal pathways. SCS also increases the expression levels of lysosome-associated membrane protein 2 (Lamp2) and mature cathepsin D (matu-CTSD) to restore lysosome function and promote autophagosome degradation. Light therapies utilize specific wavelengths of light to alleviate pain and promote healing. Light therapies use different types of light sources, including visible light, infrared, and ultraviolet rays. Recent advances in light therapies on chronic pain reveal that green light irradiation enhances morphine analgesic effect, mainly by increasing beta-endorphin and enkephalin levels in rats, reducing postsynaptic glutamate receptor expression and inhibiting microglia activation. A recent study using sound to mitigate pain and reports the mechanism of sound-mediated analgesic occurs through the cortical-thalamic circuitry. The study highlights that the analgesic effect of sound is solely dependent on the intensity of the sound, regardless of its nature or characteristics. In conclusion, the analgesic mechanisms of non-pharmacological interventions suggest their potential in the clinic. This article reviews the intervention methods, advantages, disadvantages and analgesic mechanisms of the above non-pharmacological interventions. The review will help to better understand the pathogenesis of chronic pain and to optimize non-pharmacological interventions for chronic pain.

Abstract:As an important social cognitive function, empathy can help people establish harmonious interpersonal relationship and better adapt to the real society. Previous studies have shown that the occurrence, development and recurrence of many neurological and psychiatric diseases are related to empathy deficit. By modulating cortical excitability, non-invasive brain stimulation techniques (transcranial magnetic stimulation and transcranial direct current stimulation) can regulate the individual’s level of empathy and alleviate the symptoms of empathy deficit. The available evidence from healthy populations shows that the activities of the medial prefrontal cortex, the primary motor cortex, the inferior frontal gyrus, the dorsolateral prefrontal cortex and the temporoparietal junction help improve cognitive empathy. The activities of the bilateral dorsolateral prefrontal cortex can also help to down-regulate the level of affective empathy, while the activities of the right temporoparietal junction can enhance self-representation and support the self-other discrimination during empathy. There is a small amount of clinical evidence suggest that enhancing the activities of the left dorsolateral prefrontal cortex and the medial prefrontal cortex can improve cognitive empathy in patients with psychiatric and neurodegenerative diseases, respectively. Future research should explore empathy intervention with different stimulus parameters and stimulus sites under a unified behavioral measurement, and further investigate the mechanism of non-invasive brain stimulation in improving empathy by integrating other neurophysiological techniques. The effects of individual differences on brain intervention should also be considered.

Abstract:Stroke has severe neuropsychological outcomes, the major one is post-stroke depression (PSD). Stroke survivors begin to show symptoms of depression within a few months of the incidence that overtime progresses to become a long-term ailment. As the pathophysiology for the progression of PSD is multifactorial and complex, it limits the understanding of the disease mechanism completely. Monoamine neurotransmitters have been suggested as one of the key factors in the development of depression in stroke patients. Repetitive transcranial magnetic stimulation (rTMS) has been considered as an efficient treatment for PSD, and is known for its non-invasiveness and minimal side effects. Meta-analyses and randomized clinical trials show that both high and low frequency rTMS significantly improved depressive symptoms in PSD patients, but the underlying mechanism is still unclear. The present review provides a general overview of rTMS stimulation protocols in PSD treatment, and highlights the role of monoamine neurotransmitters, such as serotonin, norepinephrine and dopamine, in the pathology, as well as in the treatment of PSD. By activating local monoamine neurotransmitters release, rTMS enhances the top-down control of prefrontal cortex and alters functional connections of multiple brain areas, which are associated with improvement of depression in the stroke patients. Moreover, rTMS has been shown to enhance glucose metabolism levels, and inhibit monoamine oxidase (MAO)-A activity through the Sirt1/MAO-A pathway. The decreased MAO-A leads to less degeneration of monoamine neurotransmitter, and provides neuroprotection. rTMS could also induce long-term potentiation or long-term depression, which leads to alterations in synaptic plasticity. As the result, brain networks connections become similar to those of normal individuals, and the long-term therapeutic effects of rTMS are maintained. In addition, brain-derived neurotrophic factor (BDNF) is also shown increased after rTMS in PSD patients, associated with serotonin elevation. The BDNF increase, which is regulated by serotonin, improves neuronal maintenance, survival and plasticity, and further positively regulating serotoninergic neuron in PSD patients.

Abstract:Substance use disorder (SUD) is a global problem that is crucial to public health and security. Since the effective pharmaceutical agent is still largely lacking, behavioral therapy, psychotherapy, or rehabilitation has been the major approach for the treatment of SUD. In the recent years, there has been growing interest in the effectiveness of non-pharmaceutical intervention for the treatment of neurological and psychological disorders, including acupuncture, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and exercise. From both preclinical and clinical studies, the present review is focused on the studies which investigated the therapeutical potential of acupuncture, DBS, rTMS, tDCS and exercise on the withdrawal duration, craving, drug intake and comorbidity of other behavioral disorders of SUD. The review included the studies involving different substances, including opioids, psychoactive substances, nicotine, alcohol, etc. The results showed that non-pharmacological intervention enabled to significantly reduce craving, drug consumption, prolong abstinence duration and improve cognitive impairment, anxiety and depression induced by substance exposure. Additionally, pharmaceutical treatment is a main therapeutic method, but effective pharmaceutical agents are still largely lacking. Non-pharmaceutical intervention has somewhat effect and mainly used as complementary approach, lacking research on the neurobiological mechanisms. Simultaneous use of pharmaceutical treatment and non-pharmaceutical intervention have better treatment outcomes with the reduced dosage of therapeutic drugs. Although non-pharmaceutical intervention is currently used as a complementary approach, future research is required to specifically examine the neurobiological mechanism underlying the effect of non-pharmaceutical intervention on SUD and improve the technical methods of non-pharmaceutical intervention.

Abstract:There are still many problems in the diagnosis and treatment of disorders of consciousness (DoC) due to the complex etiology and individual differences. In recent years, the continuous development of imaging, electrophysiology and precision therapy technology has made a lot of substantial progress in the research of DoC, including the identification of residual consciousness in patients, the explanation of the biological mechanism of consciousness recovery, and the reconstruction of damaged neural pathways by precision therapy technology. Clinical behavioral scale assessment can be used for initial assessment of patients with DoC at the bedside, but there is a high misdiagnosis rate, and it is often combined with imaging and electrophysiological means. Oxygen-dependent functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), nuclide tracer and functional metabolism based positron emission computed tomography (PET), and high-time-resolution electroencephalography (EEG) can improve the sensitivity and accuracy of the diagnosis and evaluation of DoC. Different imaging methods have both resting state and task state studies. The resting state was analyzed by power spectrum, graph theory, microstate and nonlinear measurement to explore the relationship between brain network and functional connectivity of brain regions in patients with different levels of consciousness. The task states induce brain activities based on different passive stimuli and active tasks, such as auditory stimulation, visual stimulation, olfactory stimulation, somatosensory stimulation, motor imagination task, question and answer task and mental arithmetic task, and further detect the hidden consciousness of patients. Recent studies on the diagnosis and evaluation of DoC show a trend of multi-modal combination, such as EEG-fMRI, EEG-fNIRS, EEG-PET, fMRI-PET, EEG-fMRI-PET, etc., which can make up for the deficiency of a single mode, deeply explore the potential consciousness of patients, and improve the efficiency of diagnosis and evaluation. The precision treatment of DoC is also constantly enriched and developed, mostly based on electrical and magnetic related neural regulation, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are the two mainstream treatment methods. Target selection is the core of tDCS and TMS, including dorsolateral prefrontal cortex (DLPFC), primary motor cortex, cerebellum and precuneus, etc. In addition, stimulation frequency is another key issue of TMS. High-frequency repetitive transcranial magnetic stimulation (rTMS) (≥5 Hz) can activate cortical excitability. Therefore, 5 Hz, 10 Hz and 20 Hz are widely used in the treatment of patients with DoC. At present, more and more attention is paid to the exploration of new therapeutic means, such as auricular vagal nerve stimulation, music therapy, etc., and gradually from single mode and single target to multi-mode and multi-target. However, due to individual differences, there are still many problems in determining the treatment plan for patients, and the neurobiological mechanism of precision therapy is still unclear. This article reviews the progress in the diagnosis and evaluation of DoC and the non-invasive precision treatment of patients, and discusses the important role of emerging technologies in detecting consciousness level and predicting consciousness recovery, and points out the shortcomings of current research in this field. It is expected to have some guiding significance for relevant researchers.

Abstract:Transcranial focused ultrasound is an effective neuromodulation technique that can deliver mechanical force in the form of sound waves non-invasively to specific areas of brain tissue to achieve the modulation and treatment of intracranial target areas, with the advantages of non-invasive, focused targets and adjustable focus. The earliest research on transcranial focused ultrasound can be traced back to the 1950s when the pioneering research of Lynn et al. laid the foundation for ultrasound research in the field of brain science. However, due to the strong acoustic attenuation and non-homogeneous nature of the skull, focused ultrasound suffers from focus shift, insufficient energy in the focal domain, and skull burns after transcranial. Early focused transcranial ultrasound studies would remove part of the cranial bone in the path of the acoustic beam. With the development of magnetic resonance imaging, electron computed tomography and multi-array phased array technology, noninvasive transcranial focusing of transcranial focused ultrasound is gradually becoming possible. Multi-array ultrasound phased arrays can correct the phase deviation and amplitude attenuation of ultrasound after transcranial, and achieve accurate and effective intracranial focusing. This paper first introduces the array arrangement of transducer elements, including periodic arrays, random arrays and spiral arrays. Periodic arrays include line arrays, rectangular surface arrays, curved surface arrays, and concentric ring arrays. Spiral arrays include the Fermat spiral, sixteen-arm spiral and Archimedean spiral. This paper summarizes the modulation methods of the phased array excitation signal, including phase correction methods and amplitude correction methods. Finally, this paper reviews and outlooks the basic research based on the self-researched phased array system and the clinical applications based on the Exablate system.

Abstract:Objective In this study, we compared the control group and the Tai Chi exercise group to evaluate the rehabilitation effect of Tai Chi exercise on Parkinson’s disease patients in the early and middle stages.Methods Forty-five patients with Parkinson’s disease were randomly divided into a control group (n=15) who did not receive intervention, Tai Chi Group 1 (n=15) adopted 24-style simplified Tai Chi exercises, 40 min each time, 3 times a week, and Tai Chi Group 2 (n=15) adopted 24-style simplified Tai Chi exercises, 60 min each time, 3 times a week. At baseline, 12 weeks, and 24 weeks after exercise, patients were evaluated with Falls Efficacy Scale (FES), timed up-to-go test (TUGT), Berg Balance Scale (BBS), Unified Parkinson’s Disease Rating Scale (UPDRS) III scores, Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Pittsburgh sleep quality index (PSQI).Results In the Tai Chi 1 group, the improvement of TUGT and BBS scores at 24 weeks compared with the baseline was statistically significant (P<0.05). In Tai Chi 2 group, the improvement of TUGT and BBS scores was statistically significant (P<0.05) at 24 weeks compared with the baseline, and the improvement of TUGT was statistically significant at 24 weeks compared with 12 weeks (P<0.05).Conclusion Tai Chi exercise can improve the balance disorder and reduce the risk of falls in patients with Parkinson’s disease in the early and middle stages.

Abstract:Objective Migraine is a complex brain dysfunction disease with a prevalence of 14.4% worldwide. Functional connectivity measures the statistical interdependences between two neural signals, and different functional connectivity patterns reflect different models of how brain regions work together. Therefore, investigating functional connectivity between different brain regions is important for understanding the pathophysiological mechanisms of migraine. Previous electroencephalogram-based functional connectivity analyses in migraine patients have mainly focused on visual and painful stimulation. We sought to investigate cortical responses to somatosensory stimulation in migraine patients during the interictal period, with the aims of better understanding the neurological dysfunction in migraine and providing clues for the prevention and treatment of migraine.Methods Twenty-three patients with migraine without aura, 10 patients with migraine with aura, and 28 healthy controls were recruited. Detailed basic data and medical history were collected from all participants, and the scale assessment was completed. All participants underwent electroencephalogram recording under median nerve somatosensory stimulation. The coherence of 68 brain regions was calculated as functional connectivity and correlations with clinical parameters were evaluated.Results Functional connectivity in migraine without aura and migraine with aura patients is atypical compared to controls under median nerve somatosensory stimulation, and the abnormal functional connectivity mainly involves areas of sensory discrimination, pain modulation, emotional cognition, and visual processing. The cerebral cortex in migraine without aura and migraine with aura patients may possess a common way of responding to somatosensory stimulation. The functional connectivity abnormalities in migraine patients have correlations with clinical features and may partly reflect the severity of migraine.Conclusion Our results provide evidence of altered functional connectivity in migraine patients under somatosensory stimulation, and suggest that the dysfunction in the brain network may be involved in the pathological process of migraine.