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Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes. [ABSTRACT FROM AUTHOR]

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self‐representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting‐state fMRI and completed the Questionnaire of Self‐Representation (QSR), which evaluates self‐assertion and self‐esteem. Resting‐state functional connectivity (RSFC) was calculated for regions implicated in self‐referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self‐awareness and positive self‐image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self‐representations over time that may be related to the positive self‐image patients have and could reflect a temporary adaptive strategy. [ABSTRACT FROM AUTHOR]

• Ketamine modulates anterior cingulate cortex (ACC) activity over minutes and hours. • Changes in ACC activity correlate with ketamine's antidepressant effects. • Ketamine's effects on anhedonia depend on modulation of dorsal and subgenual ACC. • Ketamine's action on ACC may reduce emotional pain and rumination. • Rodent and non-human primate studies are key to understanding ketamine's effects. The subdivisions of the anterior cingulate cortex (ACC) – including subgenual, perigenual and dorsal zones – are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of rapidly acting antidepressants. Infusions of ketamine induce acute (over minutes) and post-acute (over hours to days) modulations in subgenual and perigenual activity, and importantly, these changes can correlate with antidepressant efficacy. The subgenual and dorsal zones of the ACC have been specifically implicated in ketamine's anti-anhedonic effects. We emphasize the synergistic relationship between neuroimaging studies in humans and brain manipulations in animals to understand the causal relationship between changes in brain activity and therapeutic efficacy. We conclude with circuit-based perspectives on ketamine's action: first, related to ACC function in a central network mediating affective pain, and second, related to its role as the anterior node of the default mode network. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.

Background: Salience network (SN) connectivity is altered in schizophrenia, but the pathophysiological origin remains poorly understood. The goal of this multimodal neuroimaging study was to investigate the role of glutamatergic metabolism as putative mechanism underlying SN dysconnectivity in first episode psychosis (FEP) subjects. Methods: We measured glutamate + glutamine (Glx) in the dorsal anterior cingulate cortex (dACC) from 70 antipsychotic-naïve FEP subjects and 52 healthy controls (HC). The dACC was then used as seed to define positive and negative resting state functional connectivity (FC) of the SN. We used multiple regression analyses to test main effects and group interactions of Glx and FC associations. Results: dACC Glx levels did not differ between groups. Positive FC was significantly reduced in FEP compared to HC, and no group differences were found in negative FC. Group interactions of Glx-FC associations were found within the SN for positive FC, and in parietal cortices for negative FC. In HC, higher Glx levels predicted greater positive FC in the dACC and insula, and greater negative FC of the lateral parietal cortex. These relationships were weaker or absent in FEP. Conclusions: Here, we found that positive FC in the SN is already altered in medication-naïve FEP, underscoring the importance of considering both correlations and anticorrelations for characterization of pathology. Our data demonstrate that Glx and functional connectivity work differently in FEP than in HC, pointing to a possible mechanism underlying dysconnectivity in psychosis.

Resting-state functional magnetic resonance imaging (rsfMRI) is a novel approach that has the potential to examine abnormalities in the default mode network (DMN) component. Two different approaches were used in the present study to characterize the functional connectivities of various DMN components in 16 non-medicated ADHD and a similar number of TD (typically developing) children. rsfMRI data were analysed using independent component analysis (ICA) and region-of-interest (ROI) seed to voxel correlation analysis. ICA results indicated a strong coherence of the left dorsal anterior cingular cortex (dACC) with the DMN components in children with ADHD. In addition, seed-to-voxel functional connectivity analysis using the left dorsal anterior cingulate as a seed region suggested higher temporal coherence with other neural networks upon comparison with TD children. These results imply children with ADHD exhibit a higher dispersed resting state connectivity pattern in DMN and other networks. [ABSTRACT FROM AUTHOR]

Self-control training (SCT) is one way to enhance self-controlled behavior. We conducted a novel and exploratory functional magnetic resonance imaging experiment to examine how SCT affects neural responses in a situation that elicits a self-control response: anger provocation. Forty-five healthy young men and women completed two-weeks of SCT or a behavioral monitoring task and were then insulted during scanning. We found significant changes in functional activation and connectivity using a lenient error threshold, which were not observed using a stricter threshold. Activation in the posterior insula was greater for the control compared to the SCT group at post-provocation, trait aggression correlated with neural responses to SCT, and SCT was associated with specific amygdala-cortical connections. Neural changes occurred even though SCT did not affect participants' performance on an inhibition task, reports of trying to control their anger, or their experience of anger. This dissociation prevented clear interpretation about whether the neural changes were indicative of specific anger or anger control processes. Although replication with high-powered studies is needed, we provide evidence that SCT affects neural responses in the context of anger provocation. [ABSTRACT FROM AUTHOR]

Human and animal studies have shown that heavy cannabis (CB) use interacts with glutamatergic signaling. Additionally, recent studies have suggested that glutamate (Glu) may drive resting state functional connectivity (RSfc). The aims of the current preliminary study were to: 1) determine whether dorsal anterior cingulate cortex (dACC) Glu is related to RSfc between the dACC and two nodes of the reward network, the nucleus accumbens (NAc) and hippocampus (Hp); and 2) determine whether CB use interacts with the relationship between dACC Glu and RSfc. A group of 23 chronic CB users and 23 healthy controls participated in this multimodal MRI study. Glu levels were assessed in the dACC using magnetic resonance spectroscopy (MRS). Linear regression models were used to determine whether dACC Glu and CB use predicts RSfc between the dACC and the NAc and Hp. While the effect size is small, the results showed that the connectivity between the dACC and right NAc was predicted by the interaction between dACC Glu levels and monthly CB use. Additionally, while there is some suggestion that dACC Glu is correlated with dACC-hippocampal connectivity, unlike for dACC/NAc connectivity the relationship between them does not appear to be affected by CB use. These preliminary findings are significant in that they demonstrate the need for future studies with larger sample sizes to better characterize the relationship between resting state connectivity and neurochemistry as well as to characterize how CB use interacts with that relationship. [ABSTRACT FROM AUTHOR]

Introduction: We probed the neural basis of working memory in individuals with first episode of psychosis (FEP) and assessed how these neural abnormalities are associated with behavioral performance and/or core to psychosis pathophysiology.Methods: FEP (N=35) and matched controls (N=25) performed a visuospatial working memory task during fMRI acquisition. We isolated neural activity during the maintenance period and examined neural activity within regions typically engaged during a working memory task. Functional connectivity estimates were derived using psychophysiological interaction analysis. We examined correlations between brain function and behavioral performance and clinical symptomatology.Results: FEP had reduced accuracy and slower reaction times compared to controls (p<0.05, q<0.05). During the maintenance period, FEP exhibited reduced right dorsolateral prefrontal cortex (DLPFC) activation compared to controls (p=0.007, q=0.01), even when behavioral performance was matched between groups (p=0.01, q=0.03). Unlike controls, FEP failed to show increased dorsal anterior cingulate (dACC) activity with increased load level (p=0.02, q=0.06). Compared to controls, FEP showed increased negative DLPFC-dACC coupling during the maintenance period (p=0.05). Increased DLPFC activation was significantly associated with greater negative symptoms (p<0.005, q=0.02), while greater dACC activation was significantly associated with better performance in FEP (p<0.05, q<0.17).Conclusion: WM impairment in psychosis may be specific to abnormalities in the ability of frontal systems processing executive commands (DLPFC) and monitoring performance (dACC) during the maintenance of information. Our results add to accumulating evidence indicating that DLPFC abnormalities may be core to psychosis psychopathology. We also provide new insights regarding how DLPFC abnormalities may undermine dACC processing during the maintenance of information. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is characterized by biased information processing that leads to difficulties regulating negative affect, which includes difficulty decreasing negative affect as well as maladaptively increasing negative affect via cognitive processes. To examine the underlying neural correlates, we scanned depressed and never-depressed adults as they completed a cognitive reappraisal task which required decreasing negative affect while viewing a negative image (down-regulation) and increasing negative affect while viewing a neutral image (emotion generation). Compared to control participants, MDD participants had less recruitment of the dorsal anterior cingulate (dACC) and supplementary motor area (SMA) during early phases of down-regulation, the latter associated with poorer negative affect regulation. Further, MDD participants exhibited greater recruitment of the right middle temporal gyrus (MTG) during emotion generation, which was associated with lower negative affect. Dysregulated negative affect in MDD may be due to impairments in efficiently activating the dACC and SMA to meet regulation demands, and maladaptive generation of negative affect that characterizes individuals with MDD may be counteracted by compensatory activation in the MTG. Elucidating neural mechanisms that underlie the generation of negative affect in the absence of external stimuli is an important extension of previous work examining dysfunctional emotional processes in MDD. [ABSTRACT FROM AUTHOR]

We are presented with choices each day about how to invest our effort to achieve our goals. Critically, these decisions must frequently be made under conditions of incomplete information, where either the effort required or possible reward to be gained is uncertain. Such choices therefore require the development of potential value estimates to guide effortful goal-directed behavior. To date, however, the neural mechanisms for this expectation process are unknown. Here, we used computational fMRI during an effort-based decision-making task where trial-wise information about effort costs and reward magnitudes was presented separately over time, thereby allowing us to model distinct effort/reward computations as choice-relevant information unfolded. We found that ventromedial prefrontal cortex (vmPFC) encoded expected subjective value. Further, activity in dorsal anterior cingulate (dACC) and anterior insula (aI) reflected both effort discounting as well as a subjective value prediction error signal derived from trial history. While prior studies have identified these regions as being involved in effort-based decision making, these data demonstrate their specific role in the formation and maintenance of subjective value estimates as relevant information becomes available. [ABSTRACT FROM AUTHOR]

Suppression of aversive memories through memory control has historically been proposed as a central psychological defense mechanism. Inability to suppress memories is considered a central psychological trait in several psychiatric disorders, including Generalized Anxiety Disorder (GAD). Yet, few studies have attempted the focused identification of dysfunctional brain activation profiles when patients with Generalized Anxiety Disorders attempt memory control. Using a well-characterized behavioral paradigm we studied brain activation profiles in a group of adult GAD patients and well-matched healthy controls (HC). Participants learned word-association pairs before imaging. During fMRI when presented with one word of the pair, they were instructed to either suppress memory of, or retrieve the paired word. Subsequent behavioral testing indicated both GAD and HC were able to engage in the task, but attempts at memory control (suppression or retrieval) during fMRI revealed vastly different activation profiles. GAD were characterized by substantive hypo-activation signatures during both types of memory control, with effects particularly strong during suppression in brain regions including the dorsal anterior cingulate and the ventral prefrontal cortex. Attempts at memory control in GAD fail to engage brain regions to the same extent HC, providing a putative neuronal signature for a well-established psychological characteristic of the illness. [ABSTRACT FROM AUTHOR]

Humans readily sort one another into multiple social categories from mere facial features. However, the facial features used to do so are not always clear-cut because they can be associated with opponent categories (e.g., feminine male face). Recently, computational models and behavioral studies have provided indirect evidence that categorizing such faces is accomplished through dynamic competition between parallel, coactivated social categories that resolve into a stable categorical percept. Using a novel paradigm combining fMRI with real-time hand tracking, the present study examined how the brain translates diverse social cues into categorical percepts. Participants (male and female) categorized faces varying in gender and racial typicality. When categorizing atypical faces, participants' hand movements were simultaneously attracted toward the unselected category response, indexing the degree to which such faces activated the opposite category in parallel. Multivoxel pattern analyses (MVPAs) provided evidence that such social category coactivation manifested in neural patterns of the right fusiform cortex. The extent to which the hand was simultaneously attracted to the opposite gender or race category response option corresponded to increased neural pattern similarity with the average pattern associated with that category, which in turn associated with stronger engagement of the dorsal anterior cingulate cortex. The findings point to a model of social categorization in which occasionally conflicting facial features are resolved through competition between coactivated ventral-temporal cortical representations with the assistance of conflict-monitoring regions. More broadly, the results offer a promising multimodal paradigm to investigate the neural basis of "hidden", temporarily active representations in the service of a broad range of cognitive processes. [ABSTRACT FROM AUTHOR]

The ability to inhibit distracting stimuli from interfering with goaldirected behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functionalmagnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties. [ABSTRACT FROM AUTHOR]

Abstract: Emotion dysregulation is a key feature of mood and anxiety disorders. Many of these disorders also involve volumetric reductions in brain regions implicated in emotion regulation, including the dorsal anterior cingulate cortex (dACC). Investigating this relationship in healthy individuals may clarify the link between emotion regulation and volumetric reductions in this key brain region. High-resolution anatomical MRI images were used to calculate dACC volumes in 50 healthy female subjects. Trait measures of emotion regulation (cognitive reappraisal and expressive suppression) and negative affect were also obtained. As predicted, cognitive reappraisal was positively related to dACC volume, but not the volume of a control region, the ventral ACC. Expressive suppression, negative affect, and age were not related to dACC volume. These findings indicate that individual differences in cognitive reappraisal are related to individual differences in dACC volume in healthy participants. [Copyright &y& Elsevier]

Objective: Converging evidence suggests a role for the anterior cingulate cortex (ACC) in the pathophysiology of anorexia nervosa (AN). This study sought to determine whether ACC volume was affected by starvation in active AN and, if so, whether this had any clinical significance. Method: Eighteen patients with active AN and age- and gender-matched normal controls underwent magnetic resonance imaging (MRI). Sixteen patients (89%) with AN had intelligence quotients (IQ) testing at intake, 14 (78%) had repeat MRIs after weight normalization, and 10 (56%) had outcome data at 1-year posthospitalization. Results: Right dorsal ACC volume was significantly reduced in active AN patients versus controls and was correlated with lower performance IQ. While ACC normalization occurred with weight restoration, smaller change in right dorsal ACC volume prospectively predicted relapse after treatment. Conclusion: Reduced right dorsal ACC volume during active AN relates to deficits in perceptual organization and conceptual reasoning. The degree of right dorsal ACC normalization during treatment is related to outcome. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [ABSTRACT FROM AUTHOR]

Proton magnetic spectroscopy ( 1 H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmacological treatment, chronic drug use, and alcohol dependence. In contrast, the capacity of 1 H-MRS to evaluate the biochemical changes in the minutes to hours following drug consumption, which contribute to fast-acting drug-induced changes in perception, mood, cognition, and behavior, is largely unexplored. This Viewpoint highlights the utility of 1 H-MRS imaging for revealing neural mechanisms of rapid drug action in the human brain, with implications for phasic, in vivo changes in biosynthetic and catabolic pathways after drug exposure. Drawing from examples of psychostimulant drug effects, neuromodulatory input and drug-induced mood, we present strategies to optimize 1 H-MRS for noninvasively imaging fast-acting drug effects and other rapid phenomena within the living human brain. These approaches could provide powerful tools for both basic research and drug development.

Recent functional brain imaging studies, building on earlier observations, suggest a working model of brain control of the lower urinary tract. It comprises a few cerebral neural circuits that, during the storage phase, act on the midbrain periaqueductal gray to inhibit the long-loop, spinobulbospinal voiding reflex, thus promoting continence. Circuit 1, centered on the medial prefrontal cortex, appears to be concerned with conscious control of both continence and voiding. Circuit 2, centered on the dorsal anterior cingulate (midcingulate) and supplementary motor area, is concerned with emotional aspects of bladder control: desire to void or urgency with concomitant urethral sphincter activation to delay leakage. A subcortical circuit 3 has been less well studied. Circuit 1 is bilateral with a right-sided preference. Scattered studies of the connectivity of the control network suggest that white-matter damage may contribute to urinary incontinence. A few studies confirm that isolated cerebral lesions, if in the medial prefrontal cortex or its connecting pathways, may lead to incontinence. Lower urinary tract dysfunction in other neurologic diseases (normal-pressure hydrocephalus, Parkinson's disease, and multiple systems atrophy) appears consistent with the working model, and even spinal or peripheral lesions have central effects. However, this model omits the contributions of brain regions already observed in some imaging studies and therefore is certainly oversimplified., (© 2015 Elsevier B.V. All rights reserved.)

Dendritic spines provide a compartment for assembly and functional organization of synaptic machinery that plays a fundamental role in neuronal communication and neuroplasticity. Studies in humans as well as in animal models have demonstrated abnormal spine architecture in several psychiatric disorders, including depression and other stress-related illnesses. The negative impact of stress on the density and organization of spines is thought to contribute to the behavioral deficits caused by stress exposure. Moreover, there is now evidence that medication-induced recovery involves changes in synaptic plasticity and dendrite morphology, including increased expression of pre- and postsynaptic plasticity-related proteins, as well as the density and function of axo-spinous synapses. Here we review the evidence from brain imaging and postmortem studies demonstrating that depression is accompanied by structural and functional alterations of cortical and limbic brain regions, including the prefrontal cortex, hippocampus and amygdala. In addition, we present more direct evidence from basic research studies that exposure to stress alters spine morphology, function and plasticity and that antidepressants, particularly new rapid acting agents, reverse these effects. Elucidation of the signaling pathways and molecular mechanisms that control spine synapse assembly and plasticity will contribute to a better understanding of the pathophysiology of depression and development of novel, more effective therapeutic agents., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)