The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential (LTP) mechanism. The 8- burst stimulation (TBS) can be used as an LTP induction protoc...The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential (LTP) mechanism. The 8- burst stimulation (TBS) can be used as an LTP induction protocol in some experiments, but it has not been used in the models related to memory. In this work, an improved Camperi-Wang (C-W) model with the Ca2+ subsystem-induced bistability is adopted, and the TBS is simulated to be the initial stimuli of this model. With the evolution of the effects of the stimuli properties such as the cycle, the amplitude, and the duty ration on the memory mechanism of this model, the TBS can be adopted to activate working memory models and produce long-term memory. The study helps to propose the relationship between working memory and long-term memory, which lays a theoretical basis for the study of the neural mechanism of long-term memory.展开更多
Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the ...Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.展开更多
Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to t...Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.展开更多
Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuro...Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.展开更多
Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction an...BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.展开更多
Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implante...Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implanted pulse generators.These facto rs necessitate invasive surgical implantation and limit potential applications.Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications.However,device miniaturization presents a serious engineering challenge.This review presents significant advancements from several groups that have overcome this challenge and developed millimetricsized nerve stimulation devices.These are based on antennas,mini-coils,magneto-electric and optoelectronic materials,or receive ultrasound power.We highlight key design elements,findings from pilot studies,and present several considerations for future applications of these devices.展开更多
Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on pho...Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.展开更多
The connection and interaction between the eye and the brain are crucial to understanding brain disorders(Marchesi et al.,2021).Both the eye and the brain have a limited regenerative capacity as there are few progenit...The connection and interaction between the eye and the brain are crucial to understanding brain disorders(Marchesi et al.,2021).Both the eye and the brain have a limited regenerative capacity as there are few progenitor cells,and nerve cells do not replicate.Hence,neurodegeneration implicates irreversible damage to the central nervous system,as observed in several neurodegenerative diseases(Marchesi et al.,2021).展开更多
Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial dire...Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major arthroplasty.Methods In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and N2.Results 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received s-tDCS.tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,p<0.001)and N2(75.0(36.0-120.8)vs 30.0(1.3-59.3)min,F=12.55,p<0.001);the total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,p<0.001)and N2(488.5(455.5-548.5)vs 346.0(286.5-517.5)min,F=7.36,p=0.007);the deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,p<0.001)and N2(103.5(46.0-154.8)vs 57.5(23.3-106.5)min,F=8.4,p=0.004);and the percentages of light sleep and REM sleep on N1 and N2(p<0.05 for each).The postoperative depression and anxiety scores did not differ significantly between the two groups.No significant adverse events were reported.Conclusion In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures.However,this benefit was temporary and was not maintained over time.展开更多
To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,es...To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.展开更多
Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely un...Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.展开更多
To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for inves...To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).展开更多
To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE...To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE)of affective disorders.Suicidal ideation(SI)has been identified as an immediate precursor to suicide,such that reducing its severity is conducive to suicide prevention in adolescents.展开更多
Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst s...Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.展开更多
Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the eff...Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.展开更多
INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological app...INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like neuroplasticity.However,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological mechanisms.Metaplasticity refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.展开更多
To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individ...To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individuals with insomnia is associated with higher Beck Depression Inventory(BDI)scores.3 REM sleep architecture disruption is a typical symptom of insomnia.展开更多
Purpose: Umami reportedly promotes salivation. We aimed to investigate the effects of taste stimuli on slow and fast salivary secretion in humans using umami, sweet, and sour stimuli. Methods: Eight healthy women part...Purpose: Umami reportedly promotes salivation. We aimed to investigate the effects of taste stimuli on slow and fast salivary secretion in humans using umami, sweet, and sour stimuli. Methods: Eight healthy women participated between 14:00 and 15:00, taking the circadian rhythm of salivary secretion into account. The types and concentrations of the taste solutions were glutamic acid (1.7 × 10<sup>−3</sup> M), inosinic acid (9.8 × 10<sup>−3</sup> M), and guanylic acid (9.8 × 10<sup>−3</sup> M) for umami stimulation, citric acid (6.5 × 10<sup>−3</sup> M) for acidity stimulation, and sucrose (1.6 × 10<sup>−2</sup> M) for sweetness stimulation. First, the unstimulated salivary flow rate was measured. Then, 3 ml of a flavor solution was dropped under the tongue using a syringe. The saliva was expelled into an aluminum cup every minute and weighed. The first minute’s value minus 3 ml flavor solution was the stimulated salivary secretion rate produced by each flavor. The time-to-return to the initial unstimulated salivary flow rate was the duration of the stimulated saliva secretion rate. Results: The mean unstimulated salivary flow rate across participants was 0.64 ± 0.25 ml/min (range: 0.23 - 1.03 ml/min). The highest amount of saliva was induced by citric acid. There were significant differences between citric acid and the other flavor solutions (p < 0.05 for glutamic acid, inosinic acid, and sucrose;p < 0.01 for guanylic acid). There were no significant differences in duration of salivation between the flavor solutions. When the participants were divided into slow (0.45 ± 0.16 ml/min) and fast groups (0.83 ± 0.15 ml/min) based on their median resting salivary secretion rate, there were no significant differences between the two groups in the amount of saliva secreted at 1 minute after stimulation and the duration of the salivary secretion rate. Conclusion: Umami stimulation was effective in slowing salivary secretion and sustaining salivary secretion after stimulation.展开更多
Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulatio...Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.展开更多
基金supported by the National Natural Science Foundation of China(Nos.11232005 and11472104)the Ministry of Education Doctoral Foundation of China(No.20120074110020)
文摘The information stored in working memory can be transformed into the system of long-term memory due to the long-term potential (LTP) mechanism. The 8- burst stimulation (TBS) can be used as an LTP induction protocol in some experiments, but it has not been used in the models related to memory. In this work, an improved Camperi-Wang (C-W) model with the Ca2+ subsystem-induced bistability is adopted, and the TBS is simulated to be the initial stimuli of this model. With the evolution of the effects of the stimuli properties such as the cycle, the amplitude, and the duty ration on the memory mechanism of this model, the TBS can be adopted to activate working memory models and produce long-term memory. The study helps to propose the relationship between working memory and long-term memory, which lays a theoretical basis for the study of the neural mechanism of long-term memory.
基金supported by the Natural Science Foundation of Hubei Province,No.2022CBF680Independent Scientific Research Project of Wuhan University,No.2042022kf1119(both to LD)。
文摘Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.
基金the scope of the CICS-UBI projects UIDP/Multi/00709/2019,UIDB/Multi/00709/2019,UIDP/00709/2020,UIDB/00709/2020,financed by national funds through the Portuguese Foundation for Science and Technology/MCTESby funds to the PPBI-Portuguese Platform of Bio Imaging through the Project POCI-01-0145-FEDER-022122(to GB,MVP,NP)supported by a grant from the Portuguese Foundation for Science and Technology/MCTES(2021.07854.BD)(to IS)。
文摘Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.
基金supported by the Bryant Stokes Neurological Research Fund (to JM)a fellowship from Multiple Sclerosis Western Australia (MSWA)+1 种基金the Perron Institute for Neurological and Translational Sciencethe Bryant Stokes Neurological Research Fund (to JR)。
文摘Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
文摘BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.
基金funded by Western Sydney University and The University of Adelaidesupported by the Morton Cure Paralysis Fund and the Neurosurgical Research Foundation。
文摘Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implanted pulse generators.These facto rs necessitate invasive surgical implantation and limit potential applications.Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications.However,device miniaturization presents a serious engineering challenge.This review presents significant advancements from several groups that have overcome this challenge and developed millimetricsized nerve stimulation devices.These are based on antennas,mini-coils,magneto-electric and optoelectronic materials,or receive ultrasound power.We highlight key design elements,findings from pilot studies,and present several considerations for future applications of these devices.
基金supported by The Norwegian Research CouncilDepartment of Ophthalmology,Oslo University Hospital,Oslo,Norway(to TPU)+10 种基金Department of Medical Biochemistry,Oslo University Hospital,Oslo,Norway(to TPU)The Norwegian Association for the Blind and Partially Sighted(to TPU)The Ministry of Science and Technology of Taiwan,China MOST 105-2917-I-002-031,MOST 109-2917-I-564-032(to KC)The Scientific and Technological Research Council of Turkiye-TUBITAK(to KG)BrightFocus Foundation(to KSC)the Massachusetts Lions Foundation(to KSC)National Eye Institute Grant EY031696(to DFC)Harvard NeuroDiscovery Center Grant(to DFC)Department of Defense(USA)HT9425-23-1-1045(to DFC and AL)Core Grant for Vision Research from NIH/NEI to the Schepens Eye Research Institute(P30EY003790)South-Eastern Norway Regional Health Authority and the Norwegian Society of the Blind(to TPU).
文摘Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.
基金supported by grants from City University of Hong Kong,China (Project No.SRG-Fd7005632,SRG-Fd 7005854SIRG 7020058)(to LLHC)。
文摘The connection and interaction between the eye and the brain are crucial to understanding brain disorders(Marchesi et al.,2021).Both the eye and the brain have a limited regenerative capacity as there are few progenitor cells,and nerve cells do not replicate.Hence,neurodegeneration implicates irreversible damage to the central nervous system,as observed in several neurodegenerative diseases(Marchesi et al.,2021).
基金This study was supported in part by grants from the National Key R&D Program of China(2021ZD0203100 to JC)National Natural Science Foundation of China(NSFC81720108013,NSFC31771161 and NSFC81230025 to JC,NSFC81300957 and NSFC82171227 to HL,NSFC81771453 and NSFC31970937 to HZ)+6 种基金Jiangsu Provincial Special Program of Medical Science(BL2014029 to JC)Basic and Clinical Research Center in Anesthesiology of Jiangsu Provincial'Science and Education for Health'Project(JC),Zhejiang Provincial Natural Science Foundation(LY22H090019 to HL)Jiangsu Provincial Natural Science Foundation(BK20190047 to HZ)the Priority Academic Program Development of Jiangsu Higher Education Institutions(19KJA610005 to HZ)Distinguished Professor Program of Jiangsu(HZ),Jiangsu Province Innovative and Entrepreneurial Talent Program and Jiangsu Province Innovative and Entrepreneurial Team Program(HZ),Xuzhou Medical University start-up grant for excellent scientist(D2018010 and D2019025D to HZ)the Natural Science Foundation of Shanghai(21ZR1411300 to YH)Shenkang Clinical Study Foundation of Shanghai(SHDC2020CR4061 to YH).
文摘Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major arthroplasty.Methods In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and N2.Results 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received s-tDCS.tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,p<0.001)and N2(75.0(36.0-120.8)vs 30.0(1.3-59.3)min,F=12.55,p<0.001);the total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,p<0.001)and N2(488.5(455.5-548.5)vs 346.0(286.5-517.5)min,F=7.36,p=0.007);the deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,p<0.001)and N2(103.5(46.0-154.8)vs 57.5(23.3-106.5)min,F=8.4,p=0.004);and the percentages of light sleep and REM sleep on N1 and N2(p<0.05 for each).The postoperative depression and anxiety scores did not differ significantly between the two groups.No significant adverse events were reported.Conclusion In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures.However,this benefit was temporary and was not maintained over time.
基金the National Natural Science Foundation of China(81871426,81871430,82260359,U22A20303)Hebei Provincial Natural Science Foundation(H2020206263,H2020206625)STI2030-Major Projects Program(2022ZD0214500).
文摘To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.
基金The study was partly funded by the National Natural Science Foundation of China(82371490)the National Key R&D Program of China(2022YFC2503900,2022YFC2503901)+1 种基金Beijing Hundred,Thousand and Ten Thousand Talents Project(2017-CXYF-09)Beijing Health System Leading Talent Grant(2022-02-10).
文摘Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.
基金Ministry Key Project(JW0890006)Key Realm R&D Program of Guangdong Province(2019B030335001)+1 种基金Department of Science and Technology of Sichuan Province(2022NSFSC0808)Key Medical Discipline of Hangzhou,The Cultivation Project of the Province-leveled Preponderant Characteristic Discipline of Hangzhou Normal University(18JYXK046,20JYXK004).
文摘To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).
基金This study was funded by the National Key R&D Program of China(2022YFB4500600)National Natural Science Foundation of China(82271564)+1 种基金Science and Technology Projects of Guangzhou(202201010568,202201020047,2023B03J1300,2024A04J4178)Medical Scientific Research Foundation of Guangdong Province,China(A2023137).
文摘To the editor:Affective disorders,including major depressive disorder(MDD)and bipolar disorder,have emerged as the primary cause of adolescent suicide.Moreover,suicide mostly occurs in the major depressive episode(MDE)of affective disorders.Suicidal ideation(SI)has been identified as an immediate precursor to suicide,such that reducing its severity is conducive to suicide prevention in adolescents.
基金the National Natural Science Foundation of China(No.82101498 to XW)STI2030-Major Prjects of China(No.20212D0201801 to PH)+1 种基金National Natural Science Foundation of China(No.82171917 to PH,No.82090034 and 31970979 to KW and 32071054 to YT)the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University(No.2021kj19 to XW).
文摘Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.
基金supported by an unrestricted,investigator-initiated research grant by Scenery(BS),which provided the devices used.The project was sponsored by SJTU Trans-med Awards Research(2019015 to BS)Shanghai Clinical Research Centre for Mental Health(19MC191100 to BS)+3 种基金sponsored by the National Natural Science Foundation of China(81771482)supported by the Guangci Professorship Programme of Ruijin Hospital(N/A)and a Medical Research Council Senior Clinical Fellowship(MR/P008747/1)sponsored by the National Natural Science Foundation of China(82101546)the Shanghai Sailing Program(21YF1426700).The funding sources were not involved in the design and conduct of the study。
文摘Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.
基金the Shanghai Municipal Health Commission Clinical ResearchProgram(20224Y0220)to ZBStart-up Fundfor RAPs under the Strategic Hiring Scheme(P0048866)and JJZ.
文摘INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like neuroplasticity.However,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological mechanisms.Metaplasticity refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.
基金This work is supported by the National Natural Science Foundation of China(grant/award numbers:81871430,81871426,U22A20303,82260359)Hebei Provincial Natural Science Foundation(grant/award numbers:H2020206263,H2020206625)STI2030-Major Projects Program(grant/award number:2022ZD0214500).
文摘To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individuals with insomnia is associated with higher Beck Depression Inventory(BDI)scores.3 REM sleep architecture disruption is a typical symptom of insomnia.
文摘Purpose: Umami reportedly promotes salivation. We aimed to investigate the effects of taste stimuli on slow and fast salivary secretion in humans using umami, sweet, and sour stimuli. Methods: Eight healthy women participated between 14:00 and 15:00, taking the circadian rhythm of salivary secretion into account. The types and concentrations of the taste solutions were glutamic acid (1.7 × 10<sup>−3</sup> M), inosinic acid (9.8 × 10<sup>−3</sup> M), and guanylic acid (9.8 × 10<sup>−3</sup> M) for umami stimulation, citric acid (6.5 × 10<sup>−3</sup> M) for acidity stimulation, and sucrose (1.6 × 10<sup>−2</sup> M) for sweetness stimulation. First, the unstimulated salivary flow rate was measured. Then, 3 ml of a flavor solution was dropped under the tongue using a syringe. The saliva was expelled into an aluminum cup every minute and weighed. The first minute’s value minus 3 ml flavor solution was the stimulated salivary secretion rate produced by each flavor. The time-to-return to the initial unstimulated salivary flow rate was the duration of the stimulated saliva secretion rate. Results: The mean unstimulated salivary flow rate across participants was 0.64 ± 0.25 ml/min (range: 0.23 - 1.03 ml/min). The highest amount of saliva was induced by citric acid. There were significant differences between citric acid and the other flavor solutions (p < 0.05 for glutamic acid, inosinic acid, and sucrose;p < 0.01 for guanylic acid). There were no significant differences in duration of salivation between the flavor solutions. When the participants were divided into slow (0.45 ± 0.16 ml/min) and fast groups (0.83 ± 0.15 ml/min) based on their median resting salivary secretion rate, there were no significant differences between the two groups in the amount of saliva secreted at 1 minute after stimulation and the duration of the salivary secretion rate. Conclusion: Umami stimulation was effective in slowing salivary secretion and sustaining salivary secretion after stimulation.
文摘Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.