Anterior Cingulate Cortex Area Research Articles

Neural activity for complex sounds in the marmoset anterior cingulate cortex

Vocalizations play an important role in the daily life of nonhuman primates and are likely precursors of human language. Recent functional imaging studies in the highly vocal common marmoset (Callithrix jacchus) have suggested that anterior cingulate cortex (ACC) area 32 may be a part of a vocalization-processing network but the response properties of area 32 neurons to auditory stimuli remain unknown. Here we perform electrophysiological recordings in area 32 in marmosets with high-density Neuropixels probes and characterize neuronal responses to a variety of sounds including conspecific vocalizations. Nearly half of the neurons in area 32 respond to conspecific vocalizations and other complex auditory stimuli. These responses exhibit dynamics consisting of an initially non-selective reduction in neural activity, followed by an increase in activity that immediately conveys sound selectivity. Our findings demonstrate that primate ACC area 32 processes species-specific and biologically relevant sounds.

Neuroanatomical Substrates of Circuit-Specific Cholinergic Modulation across the Primate Anterior Cingulate Cortex.

Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal and emotions. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is composed of functionally distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY. The structural substrates of cholinergic modulation of distinct ACC microcircuits and outputs to AMY are thought to depend on the laminar and subcellular localization of cholinergic receptors. The present study examines the distribution of muscarinic acetylcholine receptors, m1 and m2, on distinct excitatory and inhibitory neurons and on AMY-targeting projection neurons within ACC areas, via immunohistochemistry and injections of neural tracers into the basolateral AMY in adult rhesus monkeys of both sexes. We found that laminar densities of m1+ and m2+ expressing excitatory and inhibitory neurons depended on area and cell type. Among the ACC areas, ventral subgenual ACC A25 exhibited greater m2+ localization on presynaptic inhibitory axon terminals and greater density of m1+ and m2+ expressing AMY-targeting (tracer+) pyramidal neurons. These patterns suggest robust cholinergic disinhibition and potentiation of amygdalar outputs from the limbic ventral ACC, which may be linked to the hyperexcitability of this subgenual ACC area in depression. These findings reveal the anatomical substrate of diverse cholinergic modulation of specific ACC microcircuits and amygdalar outputs that mediate cognitive-emotional integration and dysfunctions underlying stress and affective disorders.

Caveolin-1 is essential for the increased release of glutamate in the anterior cingulate cortex in neuropathic pain mice.

Neuropathic pain has a complex pathogenesis. Here, we examined the role of caveolin-1 (Cav-1) in the anterior cingulate cortex (ACC) in a chronic constriction injury (CCI) mouse model for the enhancement of presynaptic glutamate release in chronic neuropathic pain. Cav-1 was localized in glutamatergic neurons and showed higher expression in the ACC of CCI versus sham mice. Moreover, the release of glutamate from the ACC of the CCI mice was greater than that of the sham mice. Inhibition of Cav-1 by siRNAs greatly reduced the release of glutamate of ACC, while its overexpression (induced by injecting Lenti-Cav-1) reversed this process. The chemogenetics method was then used to activate or inhibit glutamatergic neurons in the ACC area. After 21 days of injection of AAV-hM3Dq in the sham mice, the release of glutamate was increased, the paw withdrawal latency was shortened, and expression of Cav-1 in the ACC was upregulated after intraperitoneal injection of 2 mg/kg clozapine N-oxide. Injection of AAV-hM4Di in the ACC of CCI mice led to the opposite effects. Furthermore, decreasing Cav-1 in the ACC in sham mice injected with rAAV-hM3DGq did not increase glutamate release. These findings suggest that Cav-1 in the ACC is essential for enhancing glutamate release in neuropathic pain.

Hormonal contraceptive exposure relates to changes in resting state functional connectivity of anterior cingulate cortex and amygdala.

Hormonal contraceptives (HCs), nowadays one of the most used contraceptive methods, downregulate endogenous ovarian hormones, which have multiple plastic effects in the adult brain. HCs usually contain a synthetic estrogen, ethinyl-estradiol, and a synthetic progestin, which can be classified as androgenic or anti-androgenic, depending on their interaction with androgen receptors. Both the anterior cingulate cortex (ACC) and the amygdala express steroid receptors and have shown differential functionality depending on the hormonal status of the participant and the use of HC. In this work, we investigated for the first time the relationship between ACC and amygdala resting state functional connectivity (rs-FC) and HC use duration, while controlling for progestin androgenicity. A total of 231 healthy young women participated in five different magnetic resonance imaging studies and were included in the final analysis. The relation between HC use duration and (i) gray matter volume, (ii) fractional amplitude of low-frequency fluctuations, and (iii) seed-based connectivity during resting state in the amygdalae and ACC was investigated in this large sample of women. In general, rs-FC of the amygdalae with frontal areas, and between the ACC and temporoparietal areas, decreased the longer the HC exposure and independently of the progestin's androgenicity. The type of HC's progestin did show a differential effect in the gray matter volume of left ACC and the connectivity between bilateral ACC and the right inferior frontal gyrus.

Effects of exercise intensity on the reactive astrocyte polarization in the medial prefrontal cortex.

Physical exercise contributes to neuroplasticity by promoting cognitive functions, such as learning and memory. The astrocytic phenotype is closely associated with synaptic plasticity. This study aimed to determine whether astrocyte polarization and synaptic alterations in the medial prefrontal cortex (mPFC) are affected differently by high- and moderate-intensity exercise. Mice were subjected to moderate-(MIE) and high-intensity treadmill running (HIE). Memory capacity was assessed using the novel object recognition and modified Y-maze tests. For immunohistochemistry, c-Fos-positive cells were counted in the mPFC. Using western blot analysis, astrocyte phenotype markers were quantified in whole-cell lysates, and synaptic molecules were determined in the synaptosomal fraction. Exercise lengthened the approach time to novel objects regardless of intensity in the NOR test, whereas MIE only improved spatial memory. Exercise induced c-Fos expression in the anterior cingulate cortex (ACC) and c-Fos-positive cells were higher in MIE than in HIE in the ACC area. In the prelimbic/infralimbic cortex region, the number of c-Fos-positive cells were enhanced in MIE and decreased in HIE mice. The A1 astrocyte marker (C3) was increased in HIE mice, while the A2 astrocyte markers were enhanced in exercised mice, regardless of the intensity. In the synaptosomal fraction, synaptic proteins were elevated by exercise regardless of intensity. These results suggest that exercise intensity affects neuronal plasticity by modulating the reactive state of astrocytes in the mPFC.

Interhemispheric neural characteristics of noxious mechano-nociceptive stimulation in the anterior cingulate cortex.

Pain is an unpleasant sensory and emotional experience. One of the most critical regions of the brain for pain processing is the anterior cingulate cortex (ACC). Several studies have examined the role of this region in thermal nociceptive pain. However, studies on mechanical nociceptive pain have been very limited to date. Although several studies have investigated pain, the interactions between the two hemispheres are still not clear. This study aimed to investigate nociceptive mechanical pain in the ACC bilaterally. Local field potential (LFP) signals were recorded from seven male Wistar rats' ACC regions of both hemispheres. Mechanical stimulations with two intensities, high-intensity noxious (HN) and non-noxious (NN) were applied to the left hind paw. At the same time, the LFP signals were recorded bilaterally from awake and freely moving rats. The recorded signals were analyzed from different perspectives, including spectral analysis, intensity classification, evoked potential (EP) analysis, and synchrony and similarity of two hemispheres. By using spectro-temporal features and support vector machine (SVM) classifier, HN vs. no-stimulation (NS), NN vs. NS, and HN vs. NN were classified with accuracies of 89.6, 71.1, and 84.7%, respectively. Analyses of the signals from the two hemispheres showed that the EPs in the two hemispheres were very similar and occurred simultaneously; however, the correlation and phase locking value (PLV) between the two hemispheres changed significantly after HN stimulation. These variations persisted for up to 4 s after the stimulation. In contrast, variations in the PLV and correlation for NN stimulation were not significant. This study showed that the ACC area was able to distinguish the intensity of mechanical stimulation based on the power activities of neural responses. In addition, our results suggest that the ACC region is activated bilaterally due to nociceptive mechanical pain. Additionally, stimulations above the pain threshold (HN) significantly affect the synchronicity and correlation between the two hemispheres compared to non-noxious stimuli.

Chemogenetics identifies separate area 25 brain circuits involved in anhedonia and anxiety in marmosets.

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies.

Activation of TREK1 Channel in the Anterior Cingulate Cortex Improves Neuropathic Pain in a Rat Model.

Objective. To explore the biological function and mechanism of TREK1 in neuropathic pain. Thirty-two healthy rats and rats with sciatic nerve chronic press-fitting model (chronic constriction injury of the sciatic nerve, CCI) were selected. Western blot, immunofluorescence staining, and patch clamp technique were performed to explore the biological functions of TREK1. The expression of TREK1 was decreased in the CCI model. The TREK1 channel current in the CCI model was decreased. After local administration of TREK1 channel activator in the anterior cingulate cortex area, the pain behavior of CCI rats and the expression of TREK1 protein were reversed. The expression of TREK1 was downregulated in the ACC area of CCI rats and the current of TREK1 was decreased, which played an important role in the regulation of neuropathic pain.

Social threat, fronto-cingulate-limbic morphometry, and symptom course in depressed adolescents: a longitudinal investigation.

Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression. We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months. General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048). Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.

Examining the neural correlates of error awareness in a large fMRI study.

Goal-directed behavior is dependent upon the ability to detect errors and implement appropriate posterror adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex (ACC). Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (fMRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions, including the insula cortex, supramarginal gyrus (SMG), and midline structures, such as the ACC and supplementary motor area (SMA). Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions, including the insula, SMG, and SMA. Taken together, we identified a robust and reliable neural network associated with error awareness.

Gray matter volumes of the insula and anterior cingulate cortex and their dysfunctional roles in cigarette smoking

The salience network, including the insula and anterior cingulate cortex (ACC), has been implicated in nicotine addiction. Structural imaging studies have reported diminished insula and ACC gray matter volumes (GMVs) in smokers as compared to nonsmokers. However, it remains unclear how insula and ACC GMVs may relate to years of smoking, addiction severity, or behavioral traits known to dispose individuals to smoking. Here, with a dataset curated from the Human Connectome Project and voxel-based morphometry, we replicated the findings of smaller GMVs of the insula and medial prefrontal cortex, including the dorsal ACC and supplementary motor area (dACC/SMA), in (70 heavy < 209 light < 209 never) smokers matched in age, sex, and average daily number of drinks. The GMVs of the insula or dACC/SMA were not significantly correlated with years of smoking or Fagerstrom Test for Nicotine Dependence (FTND) scores. Heavy relative to never smokers demonstrated higher externalizing and internalizing scores, as evaluated by the NIH Emotion. In heavy smokers, the dACC/SMA but not insula GMV was positively correlated with both externalizing and internalizing scores. The findings together confirm volumetric changes in the salience network in heavy smokers and suggest potentially distinct dysfunctional roles of the insula and dACC/SMA in chronic smoking.

Post-error recruitment of frontal sensory cortical projections promotes attention in mice

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACAVIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACAVIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACAVIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.

Elevated lipids are associated with reduced regional brain structure in youth with bipolar disorder.

Abnormal blood lipid levels are common in bipolar disorder (BD) and correlate with mood symptoms and neurocognition. However, studies have not examined the lipid-brain structure association in BD or youth. This study examined low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglycerides, and total cholesterol (TC) levels in relation to brain structure utilizing T1-weighted images, among participants ages 13-20 with BD (n=55) and healthy controls (HC; n=47). General linear models investigated group differences in the association of lipids with anterior cingulate cortex (ACC), hippocampus, and inferior parietal lobe structure, controlling for age, sex, body mass index, and intracranial volume. For significant associations, post hoc within-group analyses were undertaken. Exploratory vertex-wise analyses further investigated group differences in the lipid-brain structure association. There were significant group differences in the association of LDL-C (β=-0.29 p=0.001), and TC (β=-0.21 p=0.016), with hippocampal volume, and triglycerides with ACC volume (β=-0.25 p=0.01) and area (β=-0.26 p=0.004). Elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC. Post hoc analyses revealed that elevated LDL-C (β=-0.27 p=0.007) and reduced HDL-C (β=0.24 p=0.01) were associated with smaller hippocampal volume in the BD group. Exclusion of BD second-generation antipsychotic users did not alter these results. Vertex-wise analyses further showed that elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC, across the cortex. Elevated lipids are associated with smaller brain structure in BD. Research evaluating lipid-brain structure associations prospectively and whether lipid optimization has salutary effects on brain structure is necessary.

Investigation of Oxtr-expressing Neurons Projecting to Nucleus Accumbens using Oxtr-ires-Cre Knock-in prairie Voles (Microtus ochrogaster)

Social bonds such as parent–infant attachment or pair bonds can be critical for mental and physical well-being. The monogamous prairie vole (Microtus ochrogaster) has proven useful for examining the neural substrates regulating social behaviors, including social bonding. Oxytocin (OXT) and oxytocin receptor (OXTR) play critical roles in alloparental care, pair bonding and consoling behavior in prairie voles. While OXTR in a few regions, such as the nucleus accumbnes (NAcc), prefrontal cortex (PFC) and anterior cingulate cortex (ACC), have been implicated in regulating these behaviors, the extent to which other OXT sensitive areas modulate social behaviors has not been investigated. The NAcc is a central hub for modulating OXTR dependent social behaviors. To identify neurons expressing Oxtr in prairie vole brain, we generated gene knock-in voles expressing Cre recombinase in tandem with Oxtr (Oxtr-ires-Cre) using CRISPR/Cas9 genome editing. We confirmed Oxtr and Cre mRNA co-localization in NAcc, validating this model. Next, we identified putative Oxtr-expressing neurons projecting to NAcc by infusing retrograde CRE-dependent EGFP AAV into NAcc and visualizing fluorescence. We found enhanced green fluorescent protein (EGFP) positive neurons in anterior olfactory nucleus, PFC, ACC, insular cortex (IC), paraventricular thalamus (PVT), basolateral amygdala (BLA), and posteromedial and posterolateral cortical amygdaloid area (PMCo, PLCo). The ACC to NAcc OXTR projection may represent a species-specific circuit since Oxtr-expressing neurons in the ACC of mice were reported not to project to the NAcc. This is the first delineation of Oxtr-expressing neural circuits in the prairie vole, and demonstrates the utility of this novel genetically modified organism for characterizing OXTR circuits involved in social behaviors.

Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.

Correlation of Functional Magnetic Resonance Imaging Response to Visual Food Stimuli With Clinical Measures in Adolescents With Restrictive Eating Disorders

PurposePrevious reports have shown limbic dysregulation in patients with restrictive eating disorders (EDs). This study investigated functional responses in brain systems to visual food stimuli and their correlation with psychological and behavioral outcomes. MethodsA total of 18 females, aged 13–18 years, who were diagnosed with anorexia nervosa (n = 11) or atypical anorexia nervosa (n = 7), completed functional magnetic resonance imaging during a visual food paradigm. Stimuli included four food types and one nonfood. Anxiety and disordered eating cognitions were assessed using the State-Trait Anxiety Inventory and Eating Attitude Test (EAT-26). Analyses were performed to obtain contrasts among different food categories and test their correlations with cognitive and behavioral scores. ResultsContrasts of foods versus nonfood generally resulted in positive responses in occipital regions and negative responses in temporal and parietal gyri. Contrast of sweets versus nonfood, in particular, elicited additional activation in the hippocampus. Contrasting sweet to nonsweet food, the orbitofrontal cortex and anterior cingulate cortex (ACC) were activated. Contrast of all foods versus nonfood had a positive correlation with State-Trait Anxiety Inventory–state scores in the orbitofrontal cortex and ACC. Finally, the sweet versus nonsweet contrast correlated positively with EAT-26 in ACC and other frontal areas. ConclusionsVisual food stimuli elicited brain responses in limbic centers, and sweet foods extended activation to other limbic domains. Sweet food contrast correlated to EAT-26 in regions comprising the default mode network tied to introspection. Thus, we conclude that visual food stimuli produce activation in limbic-regulating regions in patients with restrictive EDs that correlate with disordered-eating cognitions and behaviors.

Excitatory and aversive behaviors - electrophysiological observation of anterior cingulate cortex (ACC) in rats

Increasing activities in anterior cingulate cortex (ACC) can enhance the aversion reactions associated with noxious stimuli. It has been known that opioid receptors activation can trigger endogenous analgesic effect. This study tried to explore whether opioid receptors activation in the ACC region could reduce the aversion associated with noxious stimuli. The experimental rats were randomly divided into seven groups, Complete Freund's adjuvant (CFA) + normal saline (NS) group, normal saline (NS) + normal saline (NS) group, normal saline (NS) +DAMGO ((DAla2, NMe-Phe4, Gly-ol5)enkephinlin, μ-opioid receptor agonist) group, complete Freund's adjuvant (CFA)+ 0.01/0.04/0.2/1 μg/μl DAMGO group(n=6). The experimental period was three days. The basal value was measured on the first day. The second day, 1 μl was administered through the ACC area, and then 0.08 ml of complete Freund's adjuvant (CFA) was injected into the left hind paw of the rat. CPA response, paw withdrawal reflex latency (PWL) and electrical activity in the ACC brain region of rats were observed on the third day. ①PWL was significantly decreased in rats after CFA was injected into left hind paw compared with post-injection(P＜0.05).② In the pain side of the apparatus, it took rats less residence time than that in the non-pain side. ③ 0.04/0.2/1 μg/μl DAMGO was given before CFA-injection, C-CPA reactions could be revised significantly. ④ Given 0.04/0.2/1 μg/μl DAMGO in the ACC region could decrease the increasing discharge frequency induced by CFA in ACC neurons. The activation of the mu-opioid receptor in the ACC region alleviates the aversion induced by noxious stimulation.

Correlation between blood oxygen level dependent fMRI signal and GABA content in anterior cingulate cortex after acupuncture of Hegu (LI4)

To explore the correlation between blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) signal and neurotransmitter γ-aminobutyric acid (GABA) concentration in the prefrontal cortex area after acupuncture or Von Frey filament stimulation (epidermal stimulation) at the right Hegu (LI4). A total of 76 healthy volunteers (23 men and 53 women, 24.5±1.4 years in age) were recruited in the pre-sent study. Each volunteer received two sessions of fMRI magnetic resonance scanning (MRS) examinations, with an interval of one week between two sessions. The MRI scan sequences included pre-task MRS, resting state BOLD and task MRS, BOLD. A region of Interest (ROI) of 35 mm×30 mm×25 mm was located at the bilateral medial prefrontal cortex areas. In the two sessions of examinations, the right LI4 point was stimulated by manual acupuncture or Von Frey filament-pressing. The tasks were designed as the block design. Each block contained 3 intermittent acupoint stimulations, lasting 30 s in each stimulation and with two minutes' pause between two stimulations. The MRS data were processed by using Linear Combination (LC) Model software (for assessing GABA content), and the BOLD data of fMRI was analyzed by using SPM12 software (comparison within each group), REST1.8 (comparison between two groups), separately. Extensive deactivations were induced by both stimulations, mainly involving the midline regions as the medial prefrontal lobe, and limbic lobe. The deactivation effect of manual acupuncture stimulation was more extensive and intensive than that of Von Frey filament stimulation, especially in the medial prefrontal lobe. Data from 66 volunteers (after exclusion of 10 participants due to bigger standard deviation of GABA/Glx) showed no marked correlation between the GABA concentration and BOLD activation in the anterior cingulate cortex area in both groups(manual acupuncture stimulation group: r=－0.07, －0.08, 0.04; P=0.57, 0.88, 0.74; Von Frey filament epidermal stimulation group: r=－0.10, －0.09, －0.01; P=0.43, 0.46, 0.96). Acupuncture of LI4 elicits a stronger and broader negative activation effect in the limbic-paralimbic-neocortical network including the medial prefrontal cortex in comparison with Von Frey filament stimulation, but no apparent correlation was found between the GABA concentration and BOLD activation in the anterior cingulate cortex after manual acupuncture and Von Frey stimulation.

Functional Brain Response to Emotional Musical Stimuli in Depression, Using INLA Approach for Approximate Bayesian Inference.

Introduction:One of the vital skills which has an impact on emotional health and well-being is the regulation of emotions. In recent years, the neural basis of this process has been considered widely. One of the powerful tools for eliciting and regulating emotion is music. The Anterior Cingulate Cortex (ACC) is part of the emotional neural circuitry involved in Major Depressive Disorder (MDD). The current study uses functional Magnetic Resonance Imaging (fMRI) to examine how neural processing of emotional musical auditory stimuli is changed within the ACC in depression. Statistical inference is conducted using a Bayesian Generalized Linear Model (GLM) approach with an Integrated Nested Laplace Approximation (INLA) algorithm.Methods:A new proposed Bayesian approach was applied for assessing functional response to emotional musical auditory stimuli in a block design fMRI data with 105 scans of two healthy and depressed women. In this Bayesian approach, Unweighted Graph-Laplacian (UGL) prior was chosen for spatial dependency, and autoregressive (AR) (1) process was used for temporal correlation via pre-weighting residuals. Finally, the inference was conducted using the Integrated Nested Laplace Approximation (INLA) algorithm in the R-INLA package.Results:The results revealed that positive music, as compared to negative music, elicits stronger activation within the ACC area in both healthy and depressed subjects. In comparing MDD and Never-Depressed (ND) individuals, a significant difference was found between MDD and ND groups in response to positive music vs negative music stimuli. The activations increase from baseline to positive stimuli and decrease from baseline to negative stimuli in ND subjects. Also, a significant decrease from baseline to positive stimuli was observed in MDD subjects, but there was no significant difference between baseline and negative stimuli.Conclusion:Assessing the pattern of activations within ACC in a depressed individual may be useful in retraining the ACC and improving its function, and lead to more effective therapeutic interventions.

Pubertal development mediates the association between family environment and brain structure and function in childhood.

Psychosocial acceleration theory suggests that pubertal maturation is accelerated in response to adversity. In addition, suboptimal caregiving accelerates development of the amygdala-medial prefrontal cortex circuit. These findings may be related. Here, we assess whether associations between family environment and measures of the amygdala-medial prefrontal cortex circuit are mediated by pubertal development in more than 2000 9- and 10-year-old children from the Adolescent Brain Cognitive Development Study (http://dx.doi.org/10.15154/1412097). Using structural equation modeling, demographic, child-reported, and parent-reported data on family dynamics were compiled into a higher level family environment latent variable. Magnetic resonance imaging preprocessing and compilations were performed by the Adolescent Brain Cognitive Development Study's data analysis core. Anterior cingulate cortex (ACC) thickness, area, white matter fractional anisotropy, amygdala volume, and cingulo-opercular network-amygdala resting-state functional connectivity were assessed. For ACC cortical thickness and ACC fractional anisotropy, significant indirect effects indicated that a stressful family environment relates to more advanced pubertal stage and more mature brain structure. For cingulo-opercular network-amygdala functional connectivity, results indicated a trend in the expected direction. For ACC area, evidence for quadratic mediation by pubertal stage was found. Sex-stratified analyses suggest stronger results for girls. Despite small effect sizes, structural measures of circuits important for emotional behavior are associated with family environment and show initial evidence of accelerated pubertal development.