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Includes supplementary materials for the online appendix. The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero-ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward-related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system. This connectivity implicates it in hippocampal episodic memory, providing routes for “what,” reward and semantic schema-related information to access the hippocampus. Second, the antero-dorsal parts of the PCD (especially 31a and 23d, PCV, and also RSC) have connectivity with early visual cortical areas including those that represent spatial scenes, with the superior parietal cortex, with the pregenual anterior cingulate cortex, and with the hippocampal system. This connectivity implicates it in the “where” component for hippocampal episodic memory and for spatial navigation. The dorsal–transitional–visual (DVT) and ProStriate regions where the retrosplenial scene area is located have connectivity from early visual cortical areas to the parahippocampal scene area, providing a ventromedial route for spatial scene information to reach the hippocampus. These connectivities provide important routes for “what,” reward, and “where” scene-related information for human hippocampal episodic memory and navigation. The midcingulate cortex provides a route from the anterior dorsal parts of the PCD and the supracallosal part of the anterior cingulate cortex to premotor regions. The research was supported by the following grants to Professor J. Feng: National Key R&D Program of China (No. 2019YFA0709502); 111 Project (No. B18015); Shanghai Municipal Science and Technology Major Project, ZJLab, and Shanghai Center for Brain Science and Brain-Inspired Technology (No. 2018SHZDZX01); and National Key R&D Program of China (No. 2018YFC1312904). G.D. is supported by a Spanish National Research Project funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI) (ref. PID2019-105772GB-I00 MCIU AEI); HBP SGA3 Human Brain Project Specific Grant Agreement 3 (grant agreement no. 945539), funded by the EU H2020 FET Flagship programme; SGR Research Support Group Support (ref. 2017 SGR 1545), funded by the Catalan Agency for Management of University and Research Grants (AGAUR); Neurotwin Digital twins for model-driven non-invasive electrical brain stimulation (grant agreement ID: 101017716) funded by the EU H2020 FET Proactive Programme; euSNN European School of Network Neuroscience (grant agreement ID: 860563) funded by the EU H2020 MSCA-ITN Innovative Training Networks; CECH The Emerging Human Brain Cluster (Id. 001-P-001682) within the framework of the European Research Development Fund Operational Program of Catalonia 2014–2020; Brain-Connects: Brain Connectivity during Stroke Recovery and Rehabilitation (id. 201725.33) funded by the Fundacio La Marato TV3; Corticity, FLAG ERA JTC 2017, (ref. PCI2018-092891) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI). The funding agencies played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events, and those taking action to avoid or prevent them? In this fMRI experiment, we addressed this by investigating brain activity as a function of current and predicted painful or nonpainful thermal stimulation, and the ability of voluntary action to affect the duration of the upcoming stimulation. Participants (n = 30) performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). On action-effective trials, pressing a response button within a specified time window during S1 reduced the duration of the upcoming stimulation in S2. On action-ineffective trials, pressing the button had no effect on upcoming stimulation. Predicted pain increased activation in regions including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Region-of-interest analyses revealed that insula’s responses for predicted pain were also modulated by potential action consequences, especially in the left hemisphere, albeit without a direct relationship with motor output. Taken together, these findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead depends on the consequences of that stimulus for sensorimotor control of behavior.Significance statementDuring acute pain, the processing of an acute sensory event likely occurs in parallel with predictive processing about its relevance for current and upcoming voluntary behavior. Here, we temporally separated the functional processes underlying current and predicted pain and found that activation in regions typically implicated in acute pain is modulated both by the noxious nature of upcoming events and by the possibility to affect those events via voluntary action (a button press). Our findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead is processed in “consequence-level” terms based on what the stimulus implies for sensorimotor control of behavior.

There is increasing evidence from genetic, biochemical, pharmacological, neuroimaging and post-mortem studies that immunological dysregulation plays a crucial role in the pathogenesis of psychoses. The involvement of microglia in schizophrenia and bipolar disorder (BD) has remained controversial, however, since results from various post-mortem studies are still inconclusive. Here, we analyzed the estimated density of microglia of age-matched individuals with schizophrenia (n = 17), BD (n = 13), and non-psychiatric control subjects (n = 17) in the anterior midcingulate cortex (aMCC), a brain area putatively involved in the pathogenesis of psychoses, using ionized calcium binding adaptor molecule 1 (Iba1)—immunohistochemistry. The microglial cells displayed a homogenously distributed Iba1—staining pattern in the aMCC with slightly varying activation states in all three groups. The estimated microglial densities did not differ significantly between individuals with schizophrenia, BD and control subjects. Remarkably, when both hemispheres were investigated separately within the three groups, the density was significantly lateralized towards the right aMCC in schizophrenia (p = 0.01) and—even more evident—in BD subjects (p = 0.008). This left–right lateralization was not observed in the control group (p = 0.52). Of note, microglial density was significantly lower in BD individuals who did not commit suicide compared with BD individuals who died from suicide (p = 0.002). This difference was not observed between individuals with BD who committed suicide and controls. The results, tentatively interpreted, suggest a hitherto unknown increased lateralization of microglial density to the right hemisphere in both psychiatric groups. If confirmed in independent samples, lateralization should be considered in all post-mortem studies on microglia. Density differences between suicide and non-suicide individuals needs further elucidation.

BackgroundPositive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

SUMMARYDespite partial experimental evidence, it is a long-standing and common belief that dreams serve an emotion regulation function. Revisiting this idea, recent neuroscientific theories have proposed that emotions experienced in dreams contribute to the resolution of emotional distress (e.g. fear extinction) and preparation for future waking affective reactions. Here we addressed one emerging common prediction from these theoretical accounts, namely that experiencing fear in dreams is associated with more adapted responses to threatening signals during wakefulness. Using a stepwise approach across two studies, we first identified brain regions activated when experiencing fear in dreams and then showed that frightening dreams modulated the response of these same regions to threatening stimuli during wakefulness. As predicted, more fear in dreams was associated with reduced activation of those fear-responsive regions during wakefulness. Specifically, in Study 1, we performed serial awakenings in 18 participants recorded throughout the night with high-density EEG and asked them whether they experienced any fear in their dreams. Insula activity increased (i.e. decreased delta and increased gamma power) for dreams containing fear. In Study 2, we tested 89 participants and found that those with higher incidence of fear in their dreams showed reduced fMRI response to fear-eliciting stimuli in the insula, amygdala and midcingulate cortex, while awake. Consistent with better emotion regulation processes, the same participants also displayed increased medial prefrontal cortex activity. These findings support that emotions in dreams and wakefulness engage similar neural substrates, and substantiate a link between emotional processes occurring during sleep and emotional brain functions during wakefulness.

Contains fulltext : 215446.pdf (Publisher’s version ) (Open Access) Successfully navigating social interactions requires the precise and balanced integration of social and environmental cues. When such flexible information integration fails, maladaptive behavioral patterns arise, including excessive aggression, empathy deficits, and social withdrawal, as seen in disorders such as conduct disorder and autism spectrum disorder. One of the main hubs for the context-dependent regulation of behavior is cingulate cortex, specifically anterior cingulate cortex (ACC) and midcingulate cortex (MCC). While volumetric abnormalities of ACC and MCC have been demonstrated in patients, little is known about the exact structural changes responsible for the dysregulation of behaviors such as aggression and social withdrawal. Here, we demonstrate that the distribution of parvalbumin (PV) and somatostatin (SOM) interneurons across ACC and MCC differentially predicts aggression and social withdrawal in BALB/cJ mice. BALB/cJ mice were phenotyped for their social behavior (three-chamber task) and aggression (resident-intruder task) compared to control (BALB/cByJ) mice. In line with previous studies, BALB/cJ mice behaved more aggressively than controls. The three-chamber task revealed two sub-groups of highly-sociable versus less-sociable BALB/cJ mice. Highly-sociable BALB/cJ mice were as aggressive as the less-sociable group-in fact, they committed more acts of socially acceptable aggression (threats and harmless bites). PV and SOM immunostaining revealed that a lack of specificity in the distribution of SOM and PV interneurons across cingulate cortex coincided with social withdrawal: both control mice and highly-sociable BALB/cJ mice showed a differential distribution of PV and SOM interneurons across the sub-areas of cingulate cortex, while for less-sociable BALB/cJ mice, the distributions were near-flat. In contrast, both highly-sociable and less-sociable BALB/cJ mice had a decreased concentration of PV interneurons in MCC compared to controls, which was therefore linked to aggressive behavior. Together, these results suggest that the dynamic balance of excitatory and inhibitory activity across ACC and MCC shapes both social and aggressive behavior.

About 90% of fMRI findings on specific phobias (SP) include analysis of region of interest (ROI). This approach characterized by higher sensitivity may produce inflated results, particularly when findings are aggregated in meta‐analytic maps. Here, we conducted a systematic review and activation likelihood estimation (ALE) meta‐analysis on SP, testing the impact of the inclusion of ROI‐based studies. ALE meta‐analyses were carried out either including ROI‐based results or focusing on whole‐brain voxelwise studies exclusively. To assess the risk of bias in the neuroimaging field, we modified the Newcastle–Ottawa Scale (NOS) and measured the reliability of fMRI findings. Of the 31 selected investigations (564 patients and 485 controls) one‐third did not motivate ROI selection: five studies did not report an explicit rationale, whereas four did not cite any specific reference in this regard. Analyses including ROI‐based studies revealed differences between phobics and healthy subjects in several regions of the limbic circuit. However, when focusing on whole‐brain analysis, only the anterior midcingulate cortex differentiated SP from controls. Notably, 13 studies were labeled with low risk of bias according to the adapted NOS. The inclusion of ROI‐based results artificially inflates group differences in fMRI meta‐analyses. Moreover, a priori, well‐motivated selection of ROIs is desirable to improve quality and reproducibility in SP neuroimaging studies. Lastly, the use of modified NOS may represent a valuable way to assess and evaluate biases in fMRI studies: “low risk” of bias was reported for less than half of the included studies, indicating the need for better practices in fMRI.

International audience; The ability to integrate information across time at multiple timescales is a vital element of adaptive behavior, because it provides the capacity to link events separated in time, extract useful information from previous events and actions, and to construct plans for behavior over time. Here we make the argument that this information integration capacity is a central function of the midcingulate cortex (MCC), by reviewing the anatomical, intrinsic network, neurophysiological, and behavioral properties of MCC. The MCC is the region of the medial wall situated dorsal to the corpus callosum and sometimes referred to as dACC. It is positioned within the densely connected core network of the primate brain, with a rich diversity of cognitive, somatomotor and autonomic connections. Furthermore, the MCC shows strong local network inhibition which appears to control the metastability of the region—an established feature of many cortical networks in which the neural dynamics move through a series of quasi-stationary states. We propose that the strong local inhibition in MCC leads to particularly long dynamic state durations, and so less frequent transitions. Apparently as a result of these anatomical features and synaptic and ionic determinants, the MCC cells display the longest neuronal timescales among a range of recorded cortical areas. We conclude that the anatomical position, intrinsic properties, and local network interactions of MCC make it a uniquely positioned cortical area to perform the integration of diverse information over time that is necessary for behavioral adaptation.

Highlights • Post-mTBI fatigue relates to visual processing and effort perception. • Fatigue correlates with activity in the extrastriate cortex and left midcingulate. • CNS drive during a sustained effort correlates with post-contraction BOLD-activity. • Insular and midcingulate activation suggests changes in cortical homeostasis., Introduction Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. Methods Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. Results The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p

The human cingulate cortex (CC), included in the paralimbic cortex, participates in emotion, visceral responses, attention, cognition, and social behaviors. The CC has spindle-shaped/fusiform cell body neurons in its layer V, the von Economo neurons (VENs). VENs have further developed in primates, and the characterization of human VENs can benefit from the detailed descriptions of the shape of dendrites and spines. Here, we advance this issue and studied VENs in the anterior and midcingulate cortex from four neurologically normal adult subjects. We used the thionin technique and the adapted "single-section" Golgi method for light microscopy. Three-dimensional (3D) reconstructions were carried out for the visualization of Golgi-impregnated VENs' cell body, ascending and descending dendrites, and collateral branches. We also looked for the presence, density, and shape of spines from proximal to distal dendrites. These neurons have a similar aspect for the soma, but features of spiny dendrites evidenced a morphological heterogeneity of CC VENs. Only for the description of this continuum of shapes, we labeled the most common feature as VEN 1, which has main dendritic shafts but few branches and sparse spines. VEN 2 shows an intermediate aspect, whereas VEN 3 displays the most profuse dendritic ramification and more spines with varied shapes from proximal to distal branches. Morphometric data exemplify the dendritic features of these cells. The heterogeneity of the dendritic architecture and spines suggests additional functional implications for the synaptic and information processing in VENs in integrated networks of normal and, possibly, neurological/psychiatric conditions involving the human CC.

In response to dehydration, humans experience thirst. This subjective state is fundamental to survival as it motivates drinking, which subsequently corrects the fluid deficit. To elicit thirst, previous studies have manipulated blood chemistry to produce a physiological thirst stimulus. In the present study, we investigated whether a physiological stimulus is indeed required for thirst to be experienced. Functional MRI (fMRI) was used to scan fully hydrated participants while they imagined a state of intense thirst and while they imagined drinking to satiate thirst. Subjective ratings of thirst were significantly higher for imagining thirst compared with imagining drinking or baseline, revealing a successful dissociation of thirst from underlying physiology. The imagine thirst condition activated brain regions similar to those reported in previous studies of physiologically evoked thirst, including the anterior midcingulate cortex (aMCC), anterior insula, precentral gyrus, inferior frontal gyrus, middle frontal gyrus, and operculum, indicating a similar neural network underlies both imagined thirst and physiologically evoked thirst. Analogous brain regions were also activated during imagined drinking, suggesting the neural representation of thirst contains a drinking-related component. Finally, the aMCC showed an increase in functional connectivity with the insula during imagined thirst relative to imagined drinking, implying functional connectivity between these two regions is needed before thirst can be experienced. As a result of these findings, this study provides important insight into how the neural representation of subjective thirst is generated and how it subsequently motivates drinking behavior.

Alzheimer's research & therapy 9(1), 28 (2017). doi:10.1186/s13195-017-0259-5, Published by BioMed Central, London

A growing literature supports the existence of interactions between emotion and action in the brain, and the central participation of the anterior midcingulate cortex (aMCC) in this regard. In the present functional magnetic resonance imaging study, we sought to investigate the role of self-relevance during such interactions by varying the context in which threating pictures were presented (with guns pointed towards or away from the observer). Participants performed a simple visual detection task following exposure to such stimuli. Except for voxelwise tests, we adopted a Bayesian analysis framework which evaluated evidence for the hypotheses of interest, given the data, in a continuous fashion. Behaviorally, our results demonstrated a valence by context interaction such that there was a tendency of speeding up responses to targets after viewing threat pictures directed towards the participant. In the brain, interaction patterns that paralleled those observed behaviorally were observed most notably in the middle temporal gyrus, supplementary motor area, precentral gyrus, and anterior insula. In these regions, activity was overall greater during threat conditions relative to neutral ones, and this effect was enhanced in the directed towards context. A valence by context interaction was observed in the aMCC too, where we also observed a correlation (across participants) of evoked responses and reaction time data. Taken together, our study revealed the context-sensitive engagement of motor-related areas during emotional perception, thus supporting the idea that emotion and action interact in important ways in the brain.

Previous studies have suggested that acupuncture is effective for ameliorating itch intensity. However, factors associated with the antipruritic effects of acupuncture have yet to be clarified. In a randomized, sham-controlled, crossover trial, we investigated the antipruritic effects of acupuncture against histamine-induced itch in healthy volunteers. Autonomic changes using heart rate variability (HRV) and brain connectivity using functional magnetic resonance imaging (fMRI) were also assessed to identify physiological factors associated with the acupuncture response. Acupuncture significantly reduced itch intensity and skin blood perfusion as assessed by laser Doppler perfusion imaging compared to sham control, indicating the antipruritic effects of acupuncture. In responder and non-responder analysis, the power of normalized high frequency (HF norm) was significantly higher, while the power of normalized low frequency (LF norm) and LF/HF ratio were significantly lower in responders compared to non-responders, suggesting the acupuncture response involved parasympathetic activation. In fMRI analysis, the putamen and the posterior part of the midcingulate cortex (pMCC) were positively connected to itch and negatively correlated with itch intensity in responders. These results suggest that parasympathetic activity and functional connectivity of the putamen and pMCC could be associated with antipruritic response to acupuncture.

Planning behavior depends crucially on the ability to distinguish between the likely and unlikely consequences of an action. Formal computational models of planning postulate the existence of a neural mechanism that tracks the transition model of the environment, i.e., a model that explicitly represents the probabilities of action consequences. However, empirical findings relating to such a mechanism are scarce. Here we report the results of two electroencephalographic experiments examining the neural correlates of transition model learning. The results implicate fronto-midline theta and delta oscillations in this process and suggest a role of the anterior midcingulate cortex in planning behavior. Keywords: Planning. State prediction errors, anterior midcingulate cortex, fronto-midline theta oscillation, delta oscillations

Anterior cingulate cortex (ACC) and midcingulate cortex (MCC) have been implicated in the regulation of aggressive behaviour. For instance, patients with conduct disorder (CD) show increased levels of aggression accompanied by changes in ACC and MCC volume. However, accounts of ACC/MCC changes in CD patients have been conflicting, likely due to the heterogeneity of the studied populations. Here, we address these discrepancies by studying volumetric changes of ACC/MCC in the BALB/cJ mouse, a model of aggression, compared to an age- and gender-matched control group of BALB/cByJ mice. We quantified aggression in BALB/cJ and BALB/cByJ mice using the resident–intruder test, and related this to volumetric measures of ACC/MCC based on Nissl-stained coronal brain slices of the same animals. We demonstrate that BALB/cJ behave consistently more aggressively (shorter attack latencies, more frequent attacks, anti-social biting) than the control group, while at the same time showing an increased volume of ACC and a decreased volume of MCC. Differences in ACC and MCC volume jointly predicted a high amount of variance in aggressive behaviour, while regression with only one predictor had a poor fit. This suggests that, beyond their individual contributions, the relationship between ACC and MCC plays an important role in regulating aggressive behaviour. Finally, we show the importance of switching from the classical rodent anatomical definition of ACC as cingulate area 2 and 1 to a definition that includes the MCC and is directly homologous to higher mammalian species: clear behaviour-related differences in ACC/MCC anatomy were only observed using the homologous definition. Electronic supplementary material The online version of this article (10.1007/s00429-018-1816-9) contains supplementary material, which is available to authorized users.

The midcingulate cortex (MCC; area 24') resides in the mid-rostrocaudal part of the cingulate gyrus, and it plays important roles in nociceptive, cognitive and skeletomotor functions. The MCC has recently been shown to consist of four cortical areas (areas a24a', a24b', p24a' and p24b') in the rabbit, based on immunohistochemistry. To further characterize the organization of these areas, here we immunohistochemically identified structures immunopositive (+) for calretinin (CR) as a marker of a subpopulation of inhibitory neurons. CR+ somata were identified as multipolar and bipolar neurons. The multipolar neurons were predominant throughout the MCC. CR+ somata were present mainly in layer (L) 2/3 and L6, and CR+ fibers occurred mainly in L1, L2/3 and L6. However, there were differences in the distribution of CR+ structures in each area. CR+ somata tended to be most densely distributed in area a24a', followed by area p24a', area a24b' and area p24b'. CR+ fibers were most densely distributed in area p24a', followed by area p24b', area a24a' and area a24b'. In addition, only areas p24a' and p24b' enclosed patchy CR+ fibers and terminals in deep L2/3. These results show the distinct distribution of CR+ structures in each area of the MCC in the rabbit, suggesting that CR+ neurons may contribute to information processing for cognitive functions in somewhat different manners in each area of the MCC.

International audience; A central aim of cognitive neuroscience is to identify how different mental processes are represented in brain activity. The medial frontal cortex (MFC), which includes multiple functionally distinct cortical areas in the superior frontal and cingulate gyri 1 , is one brain region that has been linked to diverse psychological domains, i.e., sets of related psychological states with different adaptive functions 2. Clearly, different areas within MFC encode different functions, but there is a striking convergence of overlapping functions across domains in several 'hub' areas, particularly the anterior midcingulate cortex (aMCC 3). Research across species has linked activity in aMCC with multiple functions, including cognitive control 4,5 , reward-based learning and decision making 6-9 , somatic pain 10,11 , and processing of emotional 12,13 and social information 14,15. In fact, this area responds to such a variety of tasks, and so many underlying functions have been proposed to explain its responses, that it has been described as a "Rorschach test" and understanding it a "holy grail for many cognitive neuroscientists. " 16 Theories of aMCC function often explain the numerous signals in this area as components of an underlying process that operates across domains. Candidate processes have included conflict monitoring 4 , adaptive control (i.e., control processes broadly engaged by negative affect and nociception 17), cognitive effort 18 , valuation of actions 19 and control 20 , and detecting threats to survival 21 , among others. These models have value because they offer integrative explanations for aMCC engagement across multiple domains. However, measuring brain activity across domains with functional MRI (fMRI) glosses over a potential multiplicity of different local neural circuits with distinct functions 22,23. Electrophysiological and optogenetic studies of likely homologs of human aMCC provide evidence for distinct subpopulations of neurons with different functional properties 6,8,24. Recent evidence suggests that multivariate patterns of fMRI activity can, in some cases, identify representations distributed across subpopulations of cells, including identifying functionally dissociable patterns within aMCC associated with different tasks 25,26. Thus, unified accounts of aMCC function make predictions about the similarity of multivariate brain representations across domains that have not been adequately tested. If a set of domains activate representations of a single underlying process, then engaging these representations by tasks from these domain sets should produce similar patterns of brain activity in aMCC and other MFC areas. Conversely, if different domains engage an underlying pattern that is specific to each domain and not shared by other domains, this would provide evidence against a common underlying process. Here we test these predictions using a construct-validation approach grounded in psychometric theory. We investigated three constructs that engage MFC: pain, cognitive control, and negative emotion (see Methods). We sampled human fMRI data from 18 The medial frontal cortex, including anterior midcingulate cortex, has been linked to multiple psychological domains, including cognitive control, pain, and emotion. However, it is unclear whether this region encodes representations of these domains that are generalizable across studies and subdomains. Additionally, if there are generalizable representations, do they reflect a single underlying process shared across domains or multiple domain-specific processes? We decomposed multivariate patterns of functional MRI activity from 270 participants across 18 studies into study-specific, subdomain-specific, and domain-specific components and identified latent multivariate representations that generalized across subdomains but were specific to each domain. Pain representations were localized to anterior midcingulate cortex, negative emotion representations to ventromedial prefrontal cortex, and cognitive control representations to portions of the dorsal midcingulate. These findings provide evidence for medial frontal cortex representations that generalize across studies and subdomains but are specific to distinct psychological domains rather than reducible to a single underlying process.

As smartphone use has grown rapidly over recent decade, it has been a growing interest in the potential negative impact of excessive smartphone use. In this study, we aim to identify altered brain connectivity associated with excessive smartphone use, and to investigate correlations between withdrawal symptoms, cortisol concentrations, and frontostriatal connectivity. We focused on investigating functional connectivity in frontostriatal regions, including the orbitofrontal cortex (OFC), midcingulate cortex (MCC), and nucleus accumbens (NAcc), which is related to reward processing and cognitive control. We analyzed data from 38 adolescents with excessive smartphone use (SP) and 42 healthy controls (HC). In the SP group compared with HC, we observed lower functional connectivity between the right OFC and NAcc, and between the left OFC and MCC. Moreover, functional connectivity between the MCC and NAcc was greater in SP compared with HC. Subsequently, we examined the relationship between Internet use withdrawal symptoms, cortisol concentrations, and functional connectivity between the OFC and NAcc in SP and HC. We observed that more severe withdrawal symptoms were associated with higher cortisol concentrations in adolescents with excessive smartphone use. The most interesting finding was that we observed a negative correlation between OFC connectivity with the NAcc and both withdrawal symptoms and cortisol concentrations. The functional connectivity between the OFC and NAcc, and between the OFC and MCC are related to cognitive control of emotional stimuli including reward. The current study suggests that adolescents with SP had reduced functional connectivity in these regions related to cognitive control. Furthermore, Internet use withdrawal symptoms appear to elicit cortisol secretion, and this psychophysiological change may affect frontostriatal connectivity. Our findings provide important clues to understanding the effects of excessive use of smartphones on brain functional connectivity in adolescence.

Fear extinction is a powerful model of adaptive and anxiety-related maladaptive fear inhibition. This learning process is dependent upon plastic interactions between the amygdala, the anterior midcingulate cortex (aMCC), the hippocampus, and the ventromedial prefrontal cortex (vmPFC). With regard to the amygdala, the basolateral (BLA) and centromedial amygdala (CMA) serve unique roles in fear extinction. In a large sample (N = 91), the current study examined pre- to post-extinction changes in resting state functional connectivity (RSFC) of fear inhibition and expression pathways. We also examined how trait anxiety and extinction performance were associated with extinction-related changes within these neural pathways. We found stronger pre- to post-extinction RSFC in pathways known to play a role in the down-regulation of fear responses (BLA-hippocampus, aMCC-hippocampus, CMA-hippocampus, CMA-aMCC). We also found that trait anxiety was associated with strengthening of a BLA–aMCC circuit supporting fear expression following extinction learning. Furthermore, we found that physiological indices of poorer extinction learning were linked to weaker pre- to post-extinction RSFC of a BLA–hippocampus pathway important for fear extinction consolidation. Our results highlight the network changes that occur during extinction, the separable role of CMA and BLA-based circuitry and a key pathway linked to risk for anxiety pathology.

Self-control is the ability to comply with a request, to postpone acting upon a desire object or goal, and to generate socially approved behavior in the absence of external monitors. Overeating is actually the failure in self-control while feeding. However, little is known about the brain function that allows individuals to consciously control their behavior in the context of food choice. To address this issue, we used functional MRI to measure brain activity among undergraduate young females. Forty-one undergraduate female students participated in the current study. Subjects underwent the food rating task, during which they rated each food item according to their subjective perception of its taste (from Dislike it very much to Like it very much), its long term effect on health (from very unhealthy to very healthy) and decision strength to eat it (from Strong no to Strong yes). Behavioral results indicate the positive correlation between taste rating and its corresponding decision strength to eat, no matter the food is high caloric or low. Moreover, health ratings of high caloric food was negatively correlated with DEBQ-emotional eating, and taste ratings of high caloric food was positively correlated with DEBQ-external eating. Whole brain analysis of fMRI data indicates that BOLD responses in dlPFC were positively correlated with successful self-control; BOLD responses in midcingulate cortex were positively correlated with failed self-control. This study provided direct evidence that dlPFC was involved in self-control in food-related choice.

Contains fulltext : 201119.pdf (Publisher’s version ) (Closed access) 2 p.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC–ACC connectivity and hyperactivity, and between aMCC–precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

When deprived of compelling perceptual input, the mind is often occupied with thoughts unrelated to the immediate environment. Previous behavioral research has shown that this self-generated task-unrelated thought (TUT), especially under non-demanding conditions, relates to cognitive capacities such as creativity, planning, and reduced temporal discounting. Despite the frequency and importance of this type of cognition, little is known about its structural brain basis. Using MRI-based cortical thickness measures in 37 participants, we were able to show that individuals with a higher tendency to engage in TUT under low-demanding conditions (but not under high-demanding conditions) show an increased thickness of medial prefrontal cortex (mPFC) and anterior/midcingulate cortex. Thickness of these regions also related to less temporal discounting (TD) of monetary rewards in an economic task, indicative of more patient decision-making. The findings of a shared structural substrate in mPFC and anterior/midcingulate cortex underlying both TUT and TD suggest an important role of these brain regions in supporting the self-generation of information that is unrelated to the immediate environment and which may be adaptive in nature.

Functional neuroimaging studies have long implicated the mid-cingulate cortex (MCC) in conflict monitoring, but it is not clear whether its structural integrity (i.e., the gray matter volume) influences its conflict monitoring function. In this multimodal study, we used T1-weighted MRI scans as well as event-related potentials (ERPs) to test whether the MCC gray matter volume is associated with the electrocortical marker (i.e., No-go N200 ERP component) of conflict monitoring in healthy individuals. The specificity of such a relationship in health was determined in two ways: by (A) acquiring the same data from individuals with cocaine use disorder (CUD), known to have deficits in executive function including behavioral monitoring; and (B) acquiring the P300 ERP component that is linked with attention allocation and not specifically with conflict monitoring. Twenty-five (39.1 ± 8.4 years; 8 females) healthy individuals and 25 (42.7 ± 5.9 years; 6 females) individuals with CUD underwent a rewarded Go/No-go task during which the ERP data was collected, and they also underwent a structural MRI scan. The whole brain regression analysis showed a significant correlation between MCC structural integrity and the well-known ERP measure of conflict monitoring (N200, but not the P300) in healthy individuals, which was absent in CUD who were characterized by reduced MCC gray matter volume, N200 abnormalities as well as reduced task accuracy. In individuals with CUD instead, the N200 amplitude was associated with drug addiction symptomatology. These results show that the integrity of MCC volume is directly associated with the electrocortical correlates of conflict monitoring in healthy individuals, and such an association breaks down in psychopathologies that impact these brain processes. Taken together, this MCC–N200 association may serve as a biomarker of improved behavioral monitoring processes in diseased populations., Highlights • No-go N200 amplitude is correlated with gray matter volume of the midcingulate cortex in controls. • Such N200-midcingulate association is absent in individuals with cocaine use disorder (CUD). • In the CUD group, No-go N200 amplitude is correlated with withdrawal symptoms. • N200-midcingulate association can serve as a biomarker of intact conflict monitoring.

The multi-dimensional nature of pain renders difficult a holistic understanding of it. The conceptual framework of pain is said to be cognitive-evaluative, in addition to being sensory-discriminative and affective-motivational. To compare participants’ brain-behavior response before and after a six-week mindfulness-based stress reduction (MBSR) training course on mindfulness in relation to pain modulation, three questionnaires (the Dallas Pain Questionnaire, Short Form McGill Pain Questionnaire-SFMPQ, and Kentucky Inventory of Mindfulness) as well as resting-state functional magnetic resonance imaging (fMRI) were administered to participants, divided into a pain-afflicted group (N=18) and a control group (N=16). Our results showed that the pain-afflicted group experienced significantly less pain after the mindfulness treatment than before, as measured by the SFMPQ. In conjunction, an increased connection from the anterior insular cortex (AIC) to the dorsal anterior midcingulate cortex (daMCC) was observed in the post-training pain-afflicted group and a significant correlation was found between AIC-daMCC connectivity and SFMPQ scores. The results suggest that mindfulness training can modulate the brain network dynamics underlying the subjective experience of pain.

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex.

It has been argued that emotion, pain and cognitive control are functionally segregated in distinct subdivisions of the cingulate cortex. However, recent observations encourage a fundamentally different view. Imaging studies demonstrate that negative affect, pain and cognitive control activate an overlapping region of the dorsal cingulate - the anterior midcingulate cortex (aMCC). Anatomical studies reveal that the aMCC constitutes a hub where information about reinforcers can be linked to motor centres responsible for expressing affect and executing goal-directed behaviour. Computational modelling and other kinds of evidence suggest that this intimacy reflects control processes that are common to all three domains. These observations compel a reconsideration of the dorsal cingulate's contribution to negative affect and pain.

Contains fulltext : 99756.pdf (Publisher’s version ) (Open Access) Performance monitoring is an essential prerequisite of successful goal-directed behavior. Research of the last two decades implicates the anterior midcingulate cortex (aMCC) in the human medial frontal cortex and frontostriatal basal ganglia circuits in this function. Here, we addressed the function of the thalamus in detecting errors and adjusting behavior accordingly. Using diffusion-based tractography, we found that, among the thalamic nuclei, the ventral anterior (VA) and ventral lateral anterior (VLa) nuclei have the relatively strongest connectivity with the aMCC. Patients with focal thalamic lesions showed diminished error-related negativity, behavioral error detection, and posterror adjustments. When the lesions specifically affected the thalamic VA/VLa nuclei, these effects were significantly pronounced, which was reflected by the complete absence of the error-related negativity. These results reveal that the thalamus, particularly its VA/VLa region, is a necessary constituent of the performance-monitoring network, anatomically well connected and functionally closely interacting with the aMCC. 9 p.

Objective: Waiting longer to receive pain increases its perceived unpleasantness by inducing 'dread'. However, it is not clear how unpredictability in the timing of the impending pain stimulus interacts with dread and whether the two factors show differential effects on the neural generators of the pain-evoked response. Methods: We manipulated the duration of anticipation of laser-induced pain independently of unpredictability of stimulus delivery timing, to observe the relative effect on P2 amplitudes of the laser-evoked potential (LEP) response and its estimated sources. Results: Subjects (n = 12) reported increased pain ratings after longer pain anticipation, irrespective of unpredictability in the timing of stimulus delivery. By contrast, unpredictability in stimulus timing increased the amplitude of the P2 irrespective of anticipation duration. The modulation of P2 amplitude by unpredictability was localized to midcingulate cortex (MCC) and ipsilateral secondary somatosensory (S2) areas. Greater anticipation duration increased activity in a hippocampal-insula-prefrontal network but not in MCC areas. Conclusions: Distinct neural networks contribute to the P2 and are differentially affected by pain anticipation duration and unpredictability in stimulus timing. Significance: ERP research into dread should be careful to appreciate the neural generators of pain-evoked responses and their potential modulation by unpredictability. © 2008 International Federation of Clinical Neurophysiology.

International audience; 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 anterior cingulate cortex, which is involved in cognitive and affective functioning, is important in investigating disorders in which individuals exhibit impairments in higher-order functions. In this study, we examined the anterior midcingulate cortex (aMCC) at the cellular level in patients with autism and in controls. We focused our analysis on layer V of the aMCC because it contains von Economo neurons, specialized cells thought to be involved in emotional expression and focused attention. Using a stereologic approach, we determined whether there were neuropathologic changes in von Economo neuron number, pyramidal neuron number, or pyramidal neuron size between diagnostic groups. When the groups were subdivided into young children and adolescents, pyramidal neuron and von Economo neuron numbers positively correlated with autism severity in young children, as measured by the Autism Diagnostic Interview-Revised. Young children with autism also had significantly smaller pyramidal neurons than their matched controls. Because the aMCC is involved in decision-making during uncertain situations, decreased pyramidal neuron size may reflect a potential reduction in the functional connectivity of the aMCC.