Neuropsychological Profile of a Patient with Acquired Brain Damage Following Vascular Lesion of the Left Anterior Cingulate Cortex

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. .

Study of the hippocampus and the anterior cingulate gyrus by proton MR spectroscopy in patients with post-traumatic stress disorder

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.

Biogenic Amine Neurotransmitter Response to Morphine in the Anterior Cingulate Cortex Predicts Propensity for Acquiring Self-Administration and the Intensity of the Withdrawal Syndrome

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.

H-MR Spectroscopy of the Anterior Cingulated Cortex: Usefulness in the Prediction of Patients That Will Benefit from a Cognitive Behavioural Therapy in the Treatment of Chronic Pain

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.

Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients

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.

Proton magnetic resonance spectroscopy of the anterior cingulate gyrus and caudate nucleus in schizophrenia patients versus healthy controls

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.

THE PROJECTIONS OF NITRIC OXIDE SYNTHASE (NOS) POSITIVE NEURONS TO CINGULATE CORTEX FROM SOME BRAIN AREAS RELATING PAIN IN THE RAT

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.

Changes in the Brain’s Intrinsic Organization in the Resting State with Real-Time fMRI Neurofeedback Training of Posterior Cingulate Cortex Activity

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.

Role of the Dorsal Anterior Cingulate Cortex in Relational Memory Formation: A Deep Brain Activity Index Study

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.

Contribution of the Neuroanatomy of the Cingulate Gyrus to the Neuroscientific Approach to Depression

Introduction: 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. Methodology: 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. Results: 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. Conclusion: 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.

An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in

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.

Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats

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.

Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices:Multi-electrode array recordings

Objective There is substantial evidence supporting the notion that the anterior cingulate cortex （ACC） is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation （LTP） is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli （CS） protocols. Methods A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation （TBS） paradigms were applied in layer V-VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts （4 pulses at 100 Hz） with a 200 ms interval, however, the former （TBS1） was with 10 trains and the latter （TBS2） was with 5 trains. After test stimulation at layer V-VI in the ACC, network field potentials （FPs） could be simultaneously recorded across all layers of the ACC. Results The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V-VI, in contrast, complex waveforms were localized mainly in layers II-III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS 1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II-III and layers V-VI without layer-related difference. However, no LTP was inducible in layer I. Conclusion The present findings indicate that stimulation protocols may, at least in part, account for a large portion of variations among previous LTP studies, and hence highlight the importance of selecting the best LTP induction protocol when designing such experiments. Moreover, the present results demonstrate the prominent superiority of multi-electrode array recording in revealing the network properties of synaptic activities in the ACC, especially in comparing the spatiotemporal characteristics between different layers of this structure.

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion

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.

Abnormal function of the posterior cingulate cortex in heroin addicted users during resting-state and drug-cue stimulation task

Background Previous animal and neuroimaging studies have demonstrated that brain function in heroin addicted users is impaired. However, the posterior cingulate cortex （PCC） has not received much attention. The purpose of this study was to investigate whether chronic heroin use is associated with craving-related changes in the functional connectivity of the PCC of heroin addicted users. Methods Fourteen male adult chronic heroin users and fifteen age and gender-matched healthy subjects participated in the present study. The participants underwent a resting-state functional magnetic resonance imaging （fMRI） scan and a cue-induced craving task fMRI scan. The activated PCC was identified in the cue-induced craving task by means of a group contrast test. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the correlation between brain regions. The relationship between the connectivity of specific regions and heroin dependence was investigated. Results The activation of PCC, bilateral anterior cingulate cortex, caudate, putamen, precuneus, and thalamus was significant in the heroin group compared to the healthy group in the cue-induced craving task. The detectable functional connectivity of the heroin users was stronger between the PCC and bilateral insula, bilateral dorsal striatum, right inferior parietal Iobule （IPL） and right supramarginal gyrus （P 〈0.001） compared to that of the healthy subjects in the resting-state data analysis. The strength of the functional connectivity, both for the PCC-insula （r=0.60, P 〈0.05） and for PCC-striatum （t=0.58, P 〈0.05）, was positively correlated with the duration of heroin use. Conclusion The altered functional connectivity patterns in the PCC-insula and PCC-striatum areas may be regarded as biomarkers of brain damage severity in chronic heroin users.

Activation of glycine site and GluN2B subunit of NMDA receptors is necessary for ERK/CREB signaling cascade in rostral anterior cingulate cortex in rats:Implications for affective pain

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.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

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.

Role of the Anterior Cingulate Cortex in Translational Pain Research

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.

Changes in functional connectivity of ventral anterior cingulate cortex in heroin abusers

Background Previous studies with animal experiments, autopsy, structural magnetic resonance imaging （MRI） and task-related functional MRI （fMRI） have confirmed that brain functional connectivity in addicts has become impaired. The goal of this study was to investigate the alteration of resting-state functional connectivity of the ventral anterior cingulate cortex （vACC） in the heroin abusers＇ brain. Methods Fifteen heroin abusers and fifteen matched healthy volunteers were studied using vACC as the region-of interest （ROI） seed. A 3.0 T scanner with a standard head coil was the imagining apparatus. T2＊-weighted gradient-echo planar imaging （GRE-EPI） was the scanning protocol. A ROI seed based correlation analysis used a SPM5 software package as the tool for all images processing. Results This study showed a functional connection to the insula vACC in heroin abusers. Compared with controls, heroin users showed decreased functional connectivity between the nucleus accumbens （NAc） and vACC, between the parahippocampala gyrus/amgdala （PHC/amygdala） and vACC, between the thalamus and vACC, and between the posterior cingulated cortex/precuneus （PCC/pC） and vACC. Conclusion The altered resting-state functional connectivity to the vACC suggests the neural circuitry on which the addictive drug has an affect and reflects the dysfunction of the addictive brain.

Spatial and temporal plasticity of synaptic organization in anterior cingulate cortex following peripheral inflammatory pain: multi-electrode array recordings in rats

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.