网络游戏成瘾者前扣带回功能连接静息态fMRI研究

目的 探讨青少年网络游戏成瘾者静息态下前扣带回功能连接的变化情况,从功能连接的角度解释前扣带回在网络游戏成瘾中的作用.方法 选择自2011年3月至10月在安徽医科大学附属省立医院心理门诊就诊的网络成瘾者17例为成瘾组,同期招募17例健康志愿者为正常对照组.对34例被试者一般情况进行了解并比较两组之间差异;成瘾组和正常对照组分别进行静息态fMRI扫描,数据采集后进行预处理,分别以左、右前扣带回为感兴趣脑区与全脑进行功能连接分析,比较成瘾组和正常对照组前扣带回功能连接的变化情况.结果 成瘾组每日或每周平均网络游戏时间及网络游戏渴求程度明显高于正常对照组,差异有统计学意义(P＜0.05);在静息态下,正常对照组与网络成瘾组的前扣带回都与前额叶、中后扣带回、伏核、中脑、颞叶及枕叶等脑区存在功能连接关系,与全脑其他脑区比较差异(体素差异)有统计学意义(P＜0.05);但与正常对照组比较,在静息态下成瘾组前扣带回与中脑、扣带回皮层、伏核及辅助运动区功能连接增强,与双侧前额叶、颞叶及枕叶功能连接减弱(P＜0.05).结论 网络游戏成瘾者前扣带回功能连接存在异常并可能与网络游戏成瘾的产生和维持有关.     

Potential role of the anterior cingulate cortex in PTSD: Review and hypothesis

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate—a brain region that appears to be involved in fear-conditioning—is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala-locus coeruleus-anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications. Depression and Anxiety 9:1–14, 1999. Published 1999 Wiley-Liss, Inc.     

No altered dorsal anterior cingulate activation in bipolar II disorder patients during a Go/No-go task: an fMRI study

Objectives:  It has been reported that one of the core features in patients with bipolar disorder II (BD II) is increased impulsivity. The aim of this study was to investigate whether patients with BD II showed decreased activation in the dorsal anterior cingulate cortex (dACC) as compared to healthy controls when performing a task sensitive to impulsivity.
Methods:  Twenty-seven BD II patients and 28 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Eleven of the patients were unmedicated, and possible group differences between medicated and unmedicated patients were also assessed.
Results:  The groups did not differ in behavioral performance on the Go/No-go task.
Both BD II subjects and healthy controls demonstrated dACC activity during the task, and analyses revealed no statistically significant group differences. Medicated and unmedicated patients also did not differ in the degree of fMRI activation.
Conclusions:  These findings do not support the hypothesis of abnormal dACC activity during a Go/No-go task in BD II patients.     

The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition

Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. Here, we explored the effects of being observed by others while viewing self-face images on the extent of embarrassment, and the activation and connectivity patterns in the AI and ACC. We conducted functional magnetic resonance imaging hyperscanning in pairs of healthy participants using an interaction system that allowed an individual to be observed by a partner in real time. Being observed increased the extent of embarrassment reported when viewing self-face images; a corresponding increase in self-related activity in the right AI suggested that this region played a direct role in the subjective experience. Being observed also increased the functional connectivity between the caudal ACC and prefrontal regions, which are involved in processing the reflective self. The ACC might therefore serve as a hub, integrating information about the reflective self that is used in evaluating perceptual self-face images.     

Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain

Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain‐like behaviors in sciatic nerve‐ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level‐dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve‐ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT‐3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve‐ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin‐2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain‐like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. Synapse 68:235–247, 2014 . © 2014 Wiley Periodicals, Inc.     

A functional dissociation of conflict processing within anterior cingulate cortex

Goal-directed behavior requires cognitive control to regulate the occurrence of conflict. The dorsal anterior cingulate cortex (dACC) has been suggested in detecting response conflict during various conflict tasks. Recent findings, however, have indicated not only that two distinct subregions of dACC are involved in conflict processing but also that the conflict occurs at both perceptual and response levels. In this study, we sought to examine whether perceptual and response conflicts are functionally dissociated in dACC. Thirteen healthy subjects performed a version of the Stroop task during functional magnetic resonance imaging (fMRI) scanning. We identified a functional dissociation of the caudal dACC (cdACC) and the rostral dACC (rdACC) in their responses to different sources of conflict. The cdACC was selectively engaged in perceptual conflict whereas the rdACC was more active in response conflict. Further, the dorsolateral prefrontal cortex (DLPFC) was coactivated not with cdACC but with rdACC. We suggest that cdACC plays an important role in regulative processing of perceptual conflict whereas rdACC is involved in detecting response conflict.     

Associational connections between the anterior and postetior cingulate gyrus in rabbit

Reciprocal anatomical connections between anterior and posterior divisions of the cingulate gyrus are described for the rabbit. Cells within the anterior limbic and precentral agranular regions of the rostral cingulate gyrus, predominantly from layer V, send afferebts to layer I of posterior cingulate and retrosplenial cortices. Cells from layers II and III of posterior cingulate and from layer V of retrosplenial cortex project rostrally to the anterior limbic and precentral agranular cortices. These data demonstrate the existence of an associational anatomical system connecting anterior and posterior regions of the cingulate gyrus.     

Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.

BACKGROUND: The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. METHOD: Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. RESULTS: Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. CONCLUSIONS: Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.     

Molecular mechanisms of pain in the anterior cingulate cortex

It is well known that peripheral sensory stimuli, including pain, trigger a series of neuronal activities along the somatosensory pathways as well as the neuronal network in the high brain structures. These neuronal activities not only produce appropriate physiological responses but also induce long-term plastic changes in some of the central synapses. It is believed that long-term synaptic changes help the brain to process and store new information. Such learning is critical for animals and humans to gain new knowledge of changing environment, generate appropriate emotional responses, and avoid dangerous stimuli in the future. In the case of permanent injury, however, the brain fails to distinguish the difference between "useful" and painful stimuli. Long-term synaptic changes work against the system and at least in part contribute to chronic pain. In this short article, the possible molecular mechanisms for long-term plasticity within the anterior cingulate cortex (ACC) will be discussed and reviewed, and it is hypothesized that potentiation of excitatory responses within the ACC contributes to chronic pain and pain-related mental disorders.     

Lesion‐negative anterior cingulate epilepsy

MRI‐negative anterior cingulate epilepsy is a rare entity. Herein, we describe a case of MRI and functional imaging‐negative intractable frontal lobe epilepsy in which, initially, secondary bilateral synchrony of surface and intracranial EEG and non‐lateralizing semiology rendered identification of the epileptogenic zone difficult. A staged bilateral stereotactic EEG exploration revealed a very focal, putative ictal onset zone in the right anterior cingulate gyrus, as evidenced by interictal and ictal high‐frequency oscillations (at 250 Hz) and induction of seizures from the same electrode contacts by 50‐Hz low‐intensity cortical stimulation. This was subsequently confirmed by ILAE class 1 outcome following resection of the ictal onset and irritative zones. Histopathological examination revealed focal cortical dysplasia type 1b (ILAE Commission, 2011) as the cause of epilepsy. The importance of anatomo‐electro‐clinical correlation is illustrated in this case in which semiological and electrophysiological features pointed to the anatomical localization of a challenging, MRI‐negative epilepsy. [Published with video sequence]     

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Objectives. Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. Methods. Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. Results. HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. Conclusions. Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.     

Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex

L. Sinka, E. Kovari, M. Santos, F. R. Herrmann, G. Gold, P. R. Hof, C. Bouras and P. Giannakopoulos (2012) Neuropathology and Applied Neurobiology 38, 696–709 Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex Aims: Previous neuroimaging reports described morphological and functional abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood disorders. In earlier neuropathological studies, microvascular changes that could affect brain perfusion in these disorders have rarely been studied. Here, we analysed morphological parameters of capillaries in this area in elderly cases affected by these psychiatric disorders. Methods: We analysed microvessel diameters in the dorsal and subgenual parts of the ACC in eight patients with schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with sporadic major depression, and seven age‐ and gender‐matched control cases on sections stained with modified Gallyas silver impregnation using a stereological counting approach. All individuals were drug‐naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Statistical analysis included Kruskal–Wallis group comparisons with Bonferroni correction as well as multivariate regression models. Results: Mean capillary diameter was significantly decreased in the dorsal and subgenual parts of areas 24 in bipolar and unipolar depression cases, both in layers III and V, whereas schizophrenia patients were comparable with controls. These differences persisted when controlling for age, local neuronal densities, and cortical thickness. In addition, cortical thickness was significantly smaller in both layers in schizophrenia patients. Conclusions: Our findings indicate that capillary diameters in bipolar and unipolar depression but not in schizophrenia are reduced in ACC. The significance of these findings is discussed in the light of the cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood disorders.     

Increased activation of the anterior cingulate cortex during processing of disgust faces in individuals with social phobia.

BACKGROUND: Researchers have examined the role of differential activation of various brain regions involved in processing emotional information in subjects with social phobia. These studies have focused mostly on the activation of the amygdala. The anterior cingulate cortex (ACC) also has been implicated in processing emotional information, but its role in social phobia has not been examined. METHODS: We recruited subjects with social phobia and matched them with non-anxious control subjects. Participants viewed facial expressions of disgust ("disgust faces") and neutral facial expressions ("neutral faces"). We measured brain activation, focusing on the ACC, using functional magnetic resonance imaging. We also recorded participants' ratings of emotional valence of faces, as well as response latencies to make these valence judgments. We repeated this procedure using three different sets of facial expressions. RESULTS: Individuals with social phobia exhibited a significant increase in ACC activity compared with non-anxious control subjects when processing disgust versus neutral faces. Additionally, compared with control subjects, subjects with social phobia were faster in their ratings of disgust faces and rated the neutral faces more negatively. CONCLUSIONS: Our findings demonstrate that the ACC might be involved in affective processing of negative information in socially phobic subjects.     

Functional impairment‐based segmentation of anterior cingulate cortex in depression and its relationship with treatment effects

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) is widely related to depression impairment and antidepressant treatment response. The multiplicity of ACC subdivisions calls for a fine‐grained investigation of their functional impairment and recovery profiles. We recorded resting state fMRI signals from 59 MDD patients twice before and after 12‐week antidepressant treatment, as well as 59 healthy controls (HCs). With functional connectivity (FC) between each ACC voxel and four regions of interests (bilateral dorsolateral prefrontal cortex [DLPFC] and amygdalae), subdivisions with variable impairment were identified based on groups'' dissimilarity values between MDD patients before treatment and HC. The ACC was subdivided into three impairment subdivisions named as MedialACC, DistalACC, and LateralACC according to their dominant locations. Furthermore, the impairment pattern and the recovery pattern were measured based on group statistical analyses. DistalACC impaired more on its FC with left DLPFC, whereas LateralACC showed more serious impairment on its FC with bilateral amygdalae. After treatment, FCs between DistalACC and left DLPFC, and between LateralACC and right amygdala were normalized while impaired FC between LateralACC and left amygdala kept dysfunctional. Subsequently, FC between DistalACC and left DLPFC might contribute to clinical outcome prediction. Our approach could provide an insight into how the ACC was impaired in depression and partly restored after antidepressant treatment, from the perspective of the interaction between ACC subregions and critical frontal and subcortical regions.     

Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up

Background and objectiveRepetitive transcranial magnetic stimulation (rTMS) is a first-line treatment for treatment-resistant depression (TRD). The mechanisms of action of rTMS are not fully understood, and no biomarkers are available to assist in clinical practice to predict response to rTMS. This study aimed to demonstrate that after-rTMS clinical improvement is associated with functional connectivity (FC) changes of the subgenual cingulate cortex (sgACC) and rostral anterior cingulate (rACC), and FC of sgACC and rACC might serve as potential predictors for treatment response.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were collected within 1 week before rTMS initiation in 50 TRD patients to predict subsequent response to rTMS on the left dorsolateral prefrontal cortex (DLPFC). Follow-up rs-fMRI was obtained 12 weeks after completion of rTMS and neural correlates of rTMS in sgACC- and rACC-related FC patterns were compared to before rTMS data and with rs-fMRI from healthy participants.ResultsTreatment response was associated with lower FC of sgACC to right DLPFC and higher FC of rACC to left lateral parietal cortex (IPL) measured at baseline. Using sgACC-DLPFC and rACC-IPL connectivity as features, responder-nonresponder classification accuracies of 84% and 76% (end-of-treatment), 88% and 81% (3-month follow-up), respectively were achieved. Longitudinal rs-fMRI data analyses revealed that the hyperconnectivity between sgACC and visual cortex was normalized to a level which was comparable to that of healthy participants.ConclusionsBrain activity patterns in depression are predictive of treatment response to rTMS, and longitudinal change of brain activity in relevant brain circuits after rTMS is associated with treatment response in depression. Target engagement paradigms may offer opportunities to increase the efficacy of rTMS in TRD by optimal selection of patients for treatment.Trial registrationClinicalTrials.gov Identifiers: NCT01887782 and NCT02800226.     

A meta-analysis of the anterior cingulate contribution to social pain

Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings.     

The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia.

BACKGROUND: There is strong evidence for the presence of a deficit in cortical gamma aminobutyric acid (GABA) neurotransmission in schizophrenia. In this investigation we have used the calcium binding proteins (CBPs) parvalbumin (PV), calretinin (CR), and calbindin-D28K (CB) as markers of these neuronal populations, and have characterized their pattern and density in schizophrenia, bipolar disorder (BPD), and major depressive disorder (MDD). METHODS: We examined the anterior cingulate cortex (ACC) in four groups of 15 brains each from subjects with schizophrenia, MDD, and BPD, and from control subjects. Using immunocytochemistry to identify these distinct neuronal populations, we quantified their areal density and spatial pattern organization. RESULTS: There were reductions in the density of CB-labeled neurons in layer 2 in schizophrenia (34%; p =.04) and BPD (33%; p =.05) compared with control subjects; however, after correction for multiple comparisons these findings no longer attained formal statistical significance. We observed no differences in the density of the neuronal populations labeled by CR or PV in any layer of the cortex in any disorder compared with control subjects. There was increased clustering among PV-labeled neurons in BPD compared with control subjects but no significant differences in the spatial organization of the other neuronal subpopulations in any disorder. CONCLUSIONS: The study provides some support for the presence of a deficit in GABAergic neurons in schizophrenia and shows that these changes are not specific to schizophrenia. The findings indicate that there may be a pathophysiological condition, shared by subjects with schizophrenia and BPD, which operates to selectively reduce the number or protein expression of CB-immunoreactive neurons.     

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain

Self‐regulation of brain activation using real‐time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level‐dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain‐related brain activation is site‐specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain‐evoked activation and its behavioral effects. Hum Brain Mapp 35:5784–5798, 2014. © 2014 Wiley Periodicals, Inc.     

Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words

Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients—compared to controls—encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.     

Decreased N-acetyl-aspartate levels in anterior cingulate and hippocampus in subjects with post-traumatic stress disorder: a proton magnetic resonance spectroscopy study

The purpose of this study was to investigate the concentration of N-acetyl-aspartate (NAA) in the brain and its relationship with clinical characteristics in patients with post-traumatic stress disorder (PTSD). Proton magnetic resonance spectroscopy was performed in order to measure NAA concentrations in the anterior cingulate cortex (ACC) and bilateral hippocampus in 26 subjects with fire-related PTSD, who were survivors of a subway fire in South Korea, and 25 age- and sex-matched healthy comparison subjects. There were decreased NAA levels in the ACC (t = -3.88, d.f. = 49, P < 0.001) and bilateral hippocampus (right, t = -3.88, d.f. = 49, P < 0.001; left, t = -3.62, d.f. = 49, P < 0.001) in the PTSD group relative to the healthy comparison group. Also, NAA levels of the ACC (r = -0.43, n = 26, P = 0.027) and bilateral hippocampus (right, r = -0.48, n = 26, P = 0.013; left, r = -0.40, n = 26, P = 0.04) were negatively correlated with re-experience symptom scores in subjects with PTSD. In conclusion, our findings suggest that subjects with PTSD had decreased neuronal viabilities in the ACC and bilateral hippocampus, and that these deficits may play an important role in the pathophysiology of PTSD, especially regarding the re-experiencing of traumatic events.