Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated ...Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .展开更多
Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate co...Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.展开更多
Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain la...Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.展开更多
Objective The rostral anterior cingulate cortex （rACC） is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors （NMDARs） are highly expressed in the rACC and mediate painrelated ...Objective The rostral anterior cingulate cortex （rACC） is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors （NMDARs） are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate （cAMP）/protein ki- nase A （PKA） and/or extracellular regulated kinase （ERK）/cAMP-response element-binding protein （CREB）. The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK （pERK） and phospho-CREB （pCREB） in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect.展开更多
As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterio...As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.展开更多
Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)i...Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats.Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii(NTS)and ACC,and some FOS-expressing neurons in the NTS projected to the ACC.In addition,a larger portion of ascending fibers from the NTS innervated pyramidal neurons,the neural subpopulation primarily expressing FOS under the condition of painful CP,rather than GABAergic neurons within the ACC.CP rats showed increased expression of vesicular glutamate transporter 1,and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor(NMDAR)subunit NR2B and theα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunit GluR1 within the ACC.Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats,which was similar to the analgesic effect of endomorphins injected into the ACC.Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety,whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats.Taken together,these findings provide neurocircuit,biochemical,and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats,as well as novel insights into the cortical modulation of painful CP,and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.展开更多
Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with p...Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.展开更多
To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging ...To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging were used in slice preparations of the anterior cingulate cortex （ACC） from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials （LFPs） and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation （LTP） and changes in LTP magnitude were also evaluated. We found that under naive conditions, the current sink was initially generated in layer Ⅵ, then spread to layer Ⅴ and finally confined to layers Ⅱ-Ⅲ. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers （Ⅴ-Ⅵ） to superficial layers （Ⅱ-Ⅲ） where intra- and extra- cortical inputs terminate. In the ACC slices from rats in an inflamed state （for 2 h） caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed,showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naive and saline controls. The change was more distinct in the superficial layers （Ⅱ-Ⅲ） than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers Ⅱ-Ⅲ by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.展开更多
Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initi...Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.展开更多
Anterior cingulated cortex (ACC) is involved in “the state in which patients do not care much about pain despite its presence” which is a goal of psychosomatic treatment. To investigate the absolute concentration of...Anterior cingulated cortex (ACC) is involved in “the state in which patients do not care much about pain despite its presence” which is a goal of psychosomatic treatment. To investigate the absolute concentration of N-acetylaspartate (NAA) in the anterior cingulated cortex (ACC) as predictors of patients that may benefit from cognitive behavioural therapy in the treatment of chronic pain. Proton magnetic resonance spectroscopy (1H-MRS) was performed with a 1.5 T MR system on a voxel in the bilateral ACC in 85 chronic pain patients and 20 age-matched normal control subjects. Eighteen out of 24 (75.0%) patients whose NAA concentration decreased significantly in the ACC, respectively, compared to the mean NAA concentration of the normal control subjects, needed cognitive behavioural therapy. Our results suggest that decreased NAA concentration in the ACC is associated with the necessity of cognitive behavioural therapy. 1H-MRS may serve as a useful non-invasive tool for evaluating chronic pain patients.展开更多
Major depressive disorder (MDD) is a severe, disabling pathology characterized, in addition to affective, cognitive and motor symptoms, by self-focused attention and rumination. During recursive self-focused processes...Major depressive disorder (MDD) is a severe, disabling pathology characterized, in addition to affective, cognitive and motor symptoms, by self-focused attention and rumination. During recursive self-focused processes and rumination, the posterior cingulate cortex (PCC) is activated. In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that can directly assess living biochemistry in localized brain regions. The aim of this study, therefore, was to use 1H-MRS as a means of analyzing brain metabolites in the PCC of a group of first-episode, unmedicated MDD patients. PCC metabolite levels were analyzed at 3-T in a single voxel located bilaterally over the PCC in 7 patients diagnosed for the first time with MDD and with no previous pharmacological treatment, as well as in 9 control subjects. Differences in metabolite levels between groups were compared using independent t-tests. Myo-inositol was significantly higher, and NAA + NAAG/Cr significantly lower, in MDD patients than in controls. The other brain metabolites showed no statistical differences. The present results suggest that alterations in PCC metabolite levels are likely involved in MDD pathophysiology, and may help to improve our understanding of MDD and the role of the PCC in some symptoms of depression.展开更多
Proton magnetic resonance spectroscopy （^1 H-MRS） permits the assessment of cerebral neurometabolites, such as N-acetylaspartate, choline, and creatine, in vivo and has been used to study schizophrenia. The present ...Proton magnetic resonance spectroscopy （^1 H-MRS） permits the assessment of cerebral neurometabolites, such as N-acetylaspartate, choline, and creatine, in vivo and has been used to study schizophrenia. The present study used ^1H-MRS to compare the spectroscopy change of N-acetylaspartate, creatine, and choline metabolite levels in the anterior cingulate and caudate nucleus of both schizophrenia patients and healthy controls, as well as between the left and right cerebral hemispheres in the schizophrenia patients. Results showed that N-acetylaspartate and creatine metabolite levels in the left anterior cingulate gyrus were significantly lower in the schizophrenia patients than in the healthy controls, indicating hypometabolism. In addition, choline concentration in the left caudate nucleus of schizophrenia patients was significantly lower than in the right caudate nucleus, indicating that it is necessary to study the cerebral lateralization of ^1H-MRS in schizophrenia patients.展开更多
In order to provide more foundation for explaining the mechanism of pain modulation and acupuncture analgesia by stimulating cingulate cortex, the afferent projections of NOS positive neurons of cingulate cortex were ...In order to provide more foundation for explaining the mechanism of pain modulation and acupuncture analgesia by stimulating cingulate cortex, the afferent projections of NOS positive neurons of cingulate cortex were retrograded transported by combined method of horseradish peroxidase (HRP) with nicotinamide adenosine dinucleotide phosphate doaphorase (NADPH - d) in 25 rats.The results suggested that the 5 areas of cingulate cortex received the projections of NOS positive neurons from some brain areas relating with pain modulation and acupuncture analgesia. It is possible that the fiber connections are one of the important morphological basis for acupuncture analgesia of cingulate cortex.展开更多
Itch is an unpleasant sensation that provokes the desire to scratch.While acute itch serves as a protec-tive system to warn the body of external irritating agents,chronic itch is a debilitating but poorly-treated clin...Itch is an unpleasant sensation that provokes the desire to scratch.While acute itch serves as a protec-tive system to warn the body of external irritating agents,chronic itch is a debilitating but poorly-treated clinical dis-ease leading to repetitive scratching and skin lesions.How-ever,the neural mechanisms underlying the pathophysiol-ogy of chronic itch remain mysterious.Here,we identified a cell type-dependent role of the anterior cingulate cortex(ACC)in controlling chronic itch-related excessive scratch-ing behaviors in mice.Moreover,we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area(VTA)that was critically involved in chronic itch.Furthermore,we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch.Finally,the ACC neurons were shown to predomi-nantly innervate the non-dopaminergic neurons of the VTA.Taken together,our findings uncover a cortex-midbrain cir-cuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.展开更多
Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated ...Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated that neurofeedback training alters the functional connectivity between brain regions in the task state and resting state, it is unclear how the regulation of the key hub of the default mode network (DMN) affects the topological properties of the resting-state brain network. The current study aimed to investigate what topological changes would occur in the large-scale intrinsic organization of the resting state after the real-time down-regulation of the posterior cingulate cortex (PCC). The results indicated that the down-regulation of the PCC in the DMN reduced the functional connectivity of the PCC with the nodes outside of the DMN and reduced functional connectivity between the superior medial frontal gyrus (SFGmed) and parahippocampal gyrus (PHG) in the experimental group. Moreover, the nodal graph properties of the SFGmed were reduced, while that of the PHG showed the opposite alteration after the down-regulation of the PCC. These findings possibly suggest that the regulation of the key hub of the DMN, the PCC, mainly changed the information transfer of the SFGmed and PHG.展开更多
The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fM...The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fMRI), have demonstrated that relational memory formation occurs in the ACC. However, how such memory is encoded and retrieved remains unknown due to limited time resolution of conventional fMRI. This study aimed to investigate temporal dynamics of the dorsal ACC (dACC) during word-pair tasks based on a newly developed event-related deep brain activity (ER-DBA) method using occipital electroencephalogram (EEG) signal powers. The method assesses dACC activity at a temporal resolution of approximately 0.3 s beyond the conventional resolution limit. We found that transient deactivation of dACC during the presentation of the second word of each pair was essential for encoding success regardless of whether the words were related or unrelated. We also found that memory accuracy was not affected by the intervention of inter-trials until the recall trial. Taken together, these findings suggest that dACC deactivation for encoding success is accompanied with short-term potentiation essential for durability of memory. We further found that false memory formation associated with the presentation of word pairs was occasionally committed. In such cases, dACC exhibited a similar transient deactivation although false memory commission was independent of related or unrelated conditions. Our findings suggest that encoding and retrieval of associates are paralleled and that simultaneous production of associates seems to be an essential strategy for successful relational memory formation. The study was limited to the assessment of dACC activity and did not account for other regional brain activities or receptor regulation related to short-term potentiation. We detected fast behavior of dACC during relational memory formation using the novel ER-DBA method. Such temporal dynamics will be important for eliciting underlying mechanisms of memory dysfunctions.展开更多
<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questio...<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questions leading to therapeutic applications such as focal brain stimulation. The cingulate gyrus is the primary target of these brain stimulation therapies for the treatment of depression. The objective of this work is to establish anatomoclinical correlations and to deduce the therapeutic implications. <strong>Methodology:</strong> Our work is a review of the literature. The inventory of the cingulate gyrus and depression was based on the development of a critical synthesis of bibliographic knowledge. <strong>Results:</strong> We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus. Descriptions of the cingulate gyrus boundaries are imprecise and divergent. The anterior end of the anterior cingulate cortex is a confirmed target of stimulation in the treatment of major and resistant depression, thus requiring the authors, a consensus in its delineation. Brodmann’s area 25 has been described as the main target of brain stimulation therapies. Dysfunction by local lesion or by alteration of the connectivity of Brodmann’s area has repercussions on these different structures to which it is interconnected. These disturbances when they are in the direction of collapse paint a picture similar to major depression. <strong>Conclusion: </strong>The anterior cingulate cortex is involved in depression. The functional system organization of affectivity will allow new brain stimulation techniques to act on the entire functional system or on one of its components.展开更多
The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is as...The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.展开更多
Neuropathic pain(NP)represents a considerable clinical challenge,profoundly impacting patients'quality of life.Presently,pharmacotherapy serves as a primary approach for NP alleviation,yet its efficacy often remai...Neuropathic pain(NP)represents a considerable clinical challenge,profoundly impacting patients'quality of life.Presently,pharmacotherapy serves as a primary approach for NP alleviation,yet its efficacy often remains suboptimal.Melatonin(MLT),a biologically active compound secreted by the pineal gland,has long been associated with promoting and maintaining sleep.Although recent studies suggest analgesic effects of MLT,the underlying mechanism remains largely unknown,particularly its impact on the cortex In this study,we induced an NP model in mice through spared nerve injury(SNI)and observed a considerable,dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex(ACC)administration of MLT.Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2(MT_(2)R),rather than MT_(1)R,on neurons and microglia within the ACC.Transcriptome sequencing,complemented by bioinformatics analysis,implicated MLT in the modulation of Ga(i)and immune-inflammatory signals.Specifically,MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Ga(i)signaling pathway.Simultaneously,MLT attenuated M,polarization and promoted M_(2)polarization of microglia,thereby mitigating the inflammatory response and type Il interferon response within the Acc.These findings unveil a hitherto unrecognized molecular mechanism:an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT_(2)R.This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions,offering a prospective therapeutic strategy for NP management.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
文摘Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .
基金supported by National Natural Science Fundation of China (No.30870835,30821002,and 30900444)National Basic Research Program of China (No. 2007CB512303,2007CB512502,and 2006CB500807)Postdoctoral Fundation of China (No.20080440578)
文摘Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.
基金supported by grants from the National Natural Science Foundation of China (31671091 and 81771197)the Natural Science Foundation of Jiangsu Province, China (BK20171255)the Science and Technology Planning Project of Nantong Municipality, China (MS12017023-9)
文摘Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
基金supported by the National Natural Science Foundation of China (30900444,31070973,30870835,31121061 and 30830044)
文摘Objective The rostral anterior cingulate cortex （rACC） is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors （NMDARs） are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate （cAMP）/protein ki- nase A （PKA） and/or extracellular regulated kinase （ERK）/cAMP-response element-binding protein （CREB）. The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK （pERK） and phospho-CREB （pCREB） in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect.
基金supported by the National Key R&D Program of China(2019YFA0709504)the National Natural Science Foundation of China(31930042,31771164,31900719,and 91630314)+6 种基金the Innovative Research Team of High-level Local Universities in ShanghaiDevelopment Project of Shanghai Peak Disciplines Integrated Chinese and Western MedicineShanghai Science and Technology Committee Rising-Star Program(19QA1401400)111 Project(B18015)Key Project of Shanghai Science&Technology(16JC1420402)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab。
文摘As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.
基金supported by the National Natural Science Foundations of China(81620108008 and 31971112)the Innovation Capability Support Program of Shaanxi Province,China(2021TD-57).
文摘Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats.Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii(NTS)and ACC,and some FOS-expressing neurons in the NTS projected to the ACC.In addition,a larger portion of ascending fibers from the NTS innervated pyramidal neurons,the neural subpopulation primarily expressing FOS under the condition of painful CP,rather than GABAergic neurons within the ACC.CP rats showed increased expression of vesicular glutamate transporter 1,and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor(NMDAR)subunit NR2B and theα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunit GluR1 within the ACC.Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats,which was similar to the analgesic effect of endomorphins injected into the ACC.Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety,whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats.Taken together,these findings provide neurocircuit,biochemical,and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats,as well as novel insights into the cortical modulation of painful CP,and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
基金funded by key Technology Projects in Hainan Province (Grant No.090209.zdxm2010043)
文摘Objective:To explore the characteristics of metabolic changes in patients with post-traumatic stress disorder through 1H-MRS in neuroanatomical circuit comparing with age-matches controls.Methods:Fifty patients with post-traumatic stress disorder and SO gender-and agematched normal controls were involved.The neurochemical abnormalities including the levels of choline(Cho)/ creatine(Cr) and N-acetylaspartate(NAA)/Cr were measured respectively in hippocampus and the anterior cingulate gyrus with three-dimension 1H-proton specrroscopy(3D 1H-MRS).Results:The values of NAA/Cr ratios in hippocampus and the anterior cingulate gyrus were significant lower in patients with post-traumatic stress disorder(1.71±0.32,left l.58±0.29, right 1.55±0.31) than that in controls(2.24±0.41,left 1.98±0.27,right 2.02±0.36)(P【0.05).but the values of Cho/Cr in hippocampus(left 1.64±0.23,right 1.66±0.34) were no significant with that of controls(left 1.48±0.29,right 1.54±0.38).Values of Cho/Cr in cingulate gyrus were significant higher in post-traumatic stress disorder patients(I.88±0.44) than that in controls(1.37.±0.32) (P【0.05).Conclusions:The results indicate some special neurochemical and histological structure changes in post-traumatic stress disorder patients,which might occurre earlier in anterior cingulate gyrusthe than in hippocampus.
基金supported by grants from the National Basic Research Development ProgramMinistry of Science and Technology of China(2013CB835100+3 种基金2013BAI04B04)the National Natural Science Foundation of China(8107089981171049)a Military Project of China(AWS12J004)
文摘To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging were used in slice preparations of the anterior cingulate cortex （ACC） from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials （LFPs） and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation （LTP） and changes in LTP magnitude were also evaluated. We found that under naive conditions, the current sink was initially generated in layer Ⅵ, then spread to layer Ⅴ and finally confined to layers Ⅱ-Ⅲ. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers （Ⅴ-Ⅵ） to superficial layers （Ⅱ-Ⅲ） where intra- and extra- cortical inputs terminate. In the ACC slices from rats in an inflamed state （for 2 h） caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed,showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naive and saline controls. The change was more distinct in the superficial layers （Ⅱ-Ⅲ） than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers Ⅱ-Ⅲ by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.
文摘Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.
文摘Anterior cingulated cortex (ACC) is involved in “the state in which patients do not care much about pain despite its presence” which is a goal of psychosomatic treatment. To investigate the absolute concentration of N-acetylaspartate (NAA) in the anterior cingulated cortex (ACC) as predictors of patients that may benefit from cognitive behavioural therapy in the treatment of chronic pain. Proton magnetic resonance spectroscopy (1H-MRS) was performed with a 1.5 T MR system on a voxel in the bilateral ACC in 85 chronic pain patients and 20 age-matched normal control subjects. Eighteen out of 24 (75.0%) patients whose NAA concentration decreased significantly in the ACC, respectively, compared to the mean NAA concentration of the normal control subjects, needed cognitive behavioural therapy. Our results suggest that decreased NAA concentration in the ACC is associated with the necessity of cognitive behavioural therapy. 1H-MRS may serve as a useful non-invasive tool for evaluating chronic pain patients.
基金Lily M.Granados-Dominguez received a grant from CONACYT for graduate studies.
文摘Major depressive disorder (MDD) is a severe, disabling pathology characterized, in addition to affective, cognitive and motor symptoms, by self-focused attention and rumination. During recursive self-focused processes and rumination, the posterior cingulate cortex (PCC) is activated. In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that can directly assess living biochemistry in localized brain regions. The aim of this study, therefore, was to use 1H-MRS as a means of analyzing brain metabolites in the PCC of a group of first-episode, unmedicated MDD patients. PCC metabolite levels were analyzed at 3-T in a single voxel located bilaterally over the PCC in 7 patients diagnosed for the first time with MDD and with no previous pharmacological treatment, as well as in 9 control subjects. Differences in metabolite levels between groups were compared using independent t-tests. Myo-inositol was significantly higher, and NAA + NAAG/Cr significantly lower, in MDD patients than in controls. The other brain metabolites showed no statistical differences. The present results suggest that alterations in PCC metabolite levels are likely involved in MDD pathophysiology, and may help to improve our understanding of MDD and the role of the PCC in some symptoms of depression.
文摘Proton magnetic resonance spectroscopy （^1 H-MRS） permits the assessment of cerebral neurometabolites, such as N-acetylaspartate, choline, and creatine, in vivo and has been used to study schizophrenia. The present study used ^1H-MRS to compare the spectroscopy change of N-acetylaspartate, creatine, and choline metabolite levels in the anterior cingulate and caudate nucleus of both schizophrenia patients and healthy controls, as well as between the left and right cerebral hemispheres in the schizophrenia patients. Results showed that N-acetylaspartate and creatine metabolite levels in the left anterior cingulate gyrus were significantly lower in the schizophrenia patients than in the healthy controls, indicating hypometabolism. In addition, choline concentration in the left caudate nucleus of schizophrenia patients was significantly lower than in the right caudate nucleus, indicating that it is necessary to study the cerebral lateralization of ^1H-MRS in schizophrenia patients.
文摘In order to provide more foundation for explaining the mechanism of pain modulation and acupuncture analgesia by stimulating cingulate cortex, the afferent projections of NOS positive neurons of cingulate cortex were retrograded transported by combined method of horseradish peroxidase (HRP) with nicotinamide adenosine dinucleotide phosphate doaphorase (NADPH - d) in 25 rats.The results suggested that the 5 areas of cingulate cortex received the projections of NOS positive neurons from some brain areas relating with pain modulation and acupuncture analgesia. It is possible that the fiber connections are one of the important morphological basis for acupuncture analgesia of cingulate cortex.
基金supported by grants from the National Natural Science Foundation of China(81873787,81961128024,32170994,and 82201362)Shanghai Natural Science Foundation(18ZR1424800 and 20ZR1430000)+1 种基金a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the innovative research team of high-level local universities in Shanghai.
文摘Itch is an unpleasant sensation that provokes the desire to scratch.While acute itch serves as a protec-tive system to warn the body of external irritating agents,chronic itch is a debilitating but poorly-treated clinical dis-ease leading to repetitive scratching and skin lesions.How-ever,the neural mechanisms underlying the pathophysiol-ogy of chronic itch remain mysterious.Here,we identified a cell type-dependent role of the anterior cingulate cortex(ACC)in controlling chronic itch-related excessive scratch-ing behaviors in mice.Moreover,we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area(VTA)that was critically involved in chronic itch.Furthermore,we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch.Finally,the ACC neurons were shown to predomi-nantly innervate the non-dopaminergic neurons of the VTA.Taken together,our findings uncover a cortex-midbrain cir-cuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
文摘Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated that neurofeedback training alters the functional connectivity between brain regions in the task state and resting state, it is unclear how the regulation of the key hub of the default mode network (DMN) affects the topological properties of the resting-state brain network. The current study aimed to investigate what topological changes would occur in the large-scale intrinsic organization of the resting state after the real-time down-regulation of the posterior cingulate cortex (PCC). The results indicated that the down-regulation of the PCC in the DMN reduced the functional connectivity of the PCC with the nodes outside of the DMN and reduced functional connectivity between the superior medial frontal gyrus (SFGmed) and parahippocampal gyrus (PHG) in the experimental group. Moreover, the nodal graph properties of the SFGmed were reduced, while that of the PHG showed the opposite alteration after the down-regulation of the PCC. These findings possibly suggest that the regulation of the key hub of the DMN, the PCC, mainly changed the information transfer of the SFGmed and PHG.
文摘The dorsal area of the anterior cingulate cortex (ACC) constructs the salience network associated with the anterior insular cortex. Conventional brain imaging studies, such as functional magnetic resonance imaging (fMRI), have demonstrated that relational memory formation occurs in the ACC. However, how such memory is encoded and retrieved remains unknown due to limited time resolution of conventional fMRI. This study aimed to investigate temporal dynamics of the dorsal ACC (dACC) during word-pair tasks based on a newly developed event-related deep brain activity (ER-DBA) method using occipital electroencephalogram (EEG) signal powers. The method assesses dACC activity at a temporal resolution of approximately 0.3 s beyond the conventional resolution limit. We found that transient deactivation of dACC during the presentation of the second word of each pair was essential for encoding success regardless of whether the words were related or unrelated. We also found that memory accuracy was not affected by the intervention of inter-trials until the recall trial. Taken together, these findings suggest that dACC deactivation for encoding success is accompanied with short-term potentiation essential for durability of memory. We further found that false memory formation associated with the presentation of word pairs was occasionally committed. In such cases, dACC exhibited a similar transient deactivation although false memory commission was independent of related or unrelated conditions. Our findings suggest that encoding and retrieval of associates are paralleled and that simultaneous production of associates seems to be an essential strategy for successful relational memory formation. The study was limited to the assessment of dACC activity and did not account for other regional brain activities or receptor regulation related to short-term potentiation. We detected fast behavior of dACC during relational memory formation using the novel ER-DBA method. Such temporal dynamics will be important for eliciting underlying mechanisms of memory dysfunctions.
文摘<strong>Introduction:</strong> Numerous studies show the involvement of the cingulate gyrus in affective disorders, particularly in depression. With a preventive and curative aim, the authors raise questions leading to therapeutic applications such as focal brain stimulation. The cingulate gyrus is the primary target of these brain stimulation therapies for the treatment of depression. The objective of this work is to establish anatomoclinical correlations and to deduce the therapeutic implications. <strong>Methodology:</strong> Our work is a review of the literature. The inventory of the cingulate gyrus and depression was based on the development of a critical synthesis of bibliographic knowledge. <strong>Results:</strong> We found a bipartite Brodmann subdivision which evolved into a subdivision into four regions of the cingulate gyrus. Descriptions of the cingulate gyrus boundaries are imprecise and divergent. The anterior end of the anterior cingulate cortex is a confirmed target of stimulation in the treatment of major and resistant depression, thus requiring the authors, a consensus in its delineation. Brodmann’s area 25 has been described as the main target of brain stimulation therapies. Dysfunction by local lesion or by alteration of the connectivity of Brodmann’s area has repercussions on these different structures to which it is interconnected. These disturbances when they are in the direction of collapse paint a picture similar to major depression. <strong>Conclusion: </strong>The anterior cingulate cortex is involved in depression. The functional system organization of affectivity will allow new brain stimulation techniques to act on the entire functional system or on one of its components.
基金the Beijing Nova Program of Science and Technology(20230484465)the Beijing Natural Science Foundation(J230040)+12 种基金the National Natural Science Foundation of China(82122035,81671774,81630031,and 32300933)the Sci-Tech Innovation 2030–Major Project of Brain Science and Braininspired Intelligence Technology(2021ZD0200600)the National Key R&D Program of China(2017YFC1309902)the Key Research Program of the Chinese Academy of Sciences(ZDBS-SSW-JSC006)the Scientific Foundation of Institute of Psychology,Chinese Academy of Sciences(E2CX4425YZ,E3CX1315,and Y9CX422005)the China Postdoctoral Science Foundation(2019M660847)the China National Postdoctoral Program for Innovative Talents(BX20200360)the Special Research Assistant Program of the Chinese Academy of Sciences(E2CX0624)the Key R&D Program of Sichuan Province(2023YFS0076)the Canadian Institutes of Health Research(CIHR),the National Institutes of Health–US(NIH)the Brain Canada Foundationthe Temerty Family through the Centre for Addiction and Mental Health(CAMH)Foundation and the Campbell Family Research Institutethe China Scholarship Council(202104910248)during a visit of Xiao Chen to the Centre for Addiction and Mental Health is acknowledged.
文摘The subgenual anterior cingulate cortex(sgACC)plays a central role in the pathophysiology of major depressive disorder(MDD).Its functional interactive profile with the left dorsal lateral prefrontal cortex(DLPFC)is associated with transcranial magnetic stimulation(TMS)treatment outcomes.Previous research on sgACC functional connectivity(FC)in MDD has yielded inconsistent results,partly due to small sample sizes and limited statistical power.Furthermore,calculating sgACC-FC to target TMS individually is challenging.We used a large multi-site cross-sectional sample(1660 patients with MDD vs.1341 healthy controls)from Phase Ⅱ of the Depression Imaging REsearch ConsorTium(DIRECT)to systematically delineate case-control difference maps of sgACC-FC.We explored the potential impact of group-level abnormality profiles on TMS target localization and clinical efficacy.Next,we developed an MDD big data-guided,individualized TMS targeting algorithm to integrate group-level statistical maps with individual-level brain activity to individually localize TMS targets.We found enhanced sgACCDLPFC FC in patients with MDD compared with healthy controls(HC).These group differences altered the position of the sgACC anti-correlation peak in the left DLPFC.We showed that the magnitude of case-control differences in the sgACC-FC was related to clinical improvement in two independent clinical samples.This targeting algorithm may generate targets demonstrating stronger associations with clinical efficiency than group-level targets.We reliably delineated MDD-related abnormalities of sgACC-FC profiles in a large,independently ascertained sample and demonstrated the potential impact of such casecontrol differences on FC-guided localization of TMS targets.
基金supported by grants from the National Natural Science Foundation of China(32192410 and 32071000 to T.Chen,and 81620108008 and 82130034 to Y.L.)the National Science and Technology Innovation 2030 Major Program(2021ZD0204403 to Y.L.and 2021ZD0203200-02 to L.Zhang).
文摘Neuropathic pain(NP)represents a considerable clinical challenge,profoundly impacting patients'quality of life.Presently,pharmacotherapy serves as a primary approach for NP alleviation,yet its efficacy often remains suboptimal.Melatonin(MLT),a biologically active compound secreted by the pineal gland,has long been associated with promoting and maintaining sleep.Although recent studies suggest analgesic effects of MLT,the underlying mechanism remains largely unknown,particularly its impact on the cortex In this study,we induced an NP model in mice through spared nerve injury(SNI)and observed a considerable,dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex(ACC)administration of MLT.Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2(MT_(2)R),rather than MT_(1)R,on neurons and microglia within the ACC.Transcriptome sequencing,complemented by bioinformatics analysis,implicated MLT in the modulation of Ga(i)and immune-inflammatory signals.Specifically,MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Ga(i)signaling pathway.Simultaneously,MLT attenuated M,polarization and promoted M_(2)polarization of microglia,thereby mitigating the inflammatory response and type Il interferon response within the Acc.These findings unveil a hitherto unrecognized molecular mechanism:an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT_(2)R.This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions,offering a prospective therapeutic strategy for NP management.
