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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.

The way the brain controls voluntary movements for normal and pathological subject remains puzzling. In this selective review, we provide unreported harmonies between the anterior midcingulate cortex (aMCC) activities and the ideomotor mechanism postulating that voluntary movements are controlled by the anticipation of the expected perceptual consequences of an action, critically involving bidirectional interplay of a given motor activity and corresponding sensory feedback. Among other evidence, we found that the required asymmetry in the bidirectional interplay between a given motor command and its expected sensory effect could rely on the specific activity of aMCC neurons when observing errors and successes. We confirm this hypothesis by presenting a pathological perspective, studying obsessive-compulsive and other related disorders in which hyperactivated and uniform aMCC activities should lead to a circular-reflex process that results in persistent ideas and repeated actions. By evaluating normal and pathological data, we propose considering the aMCC at a central position within the cerebral network involved in the ideomotor mechanism.

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.

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.

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.

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.

In a recent study we have demonstrated that the feedback-related negativity (FRN) reflects the integrated value of instantaneous and delayed decision consequences (Osinsky et al. 2017). In the present work, we extend this research by using a novel choice task in which instant and delayed consequence values of a single decision outcome can be manipulated independently of each other in a trial-wise manner. Fifty-nine healthy participants completed this task while EEG was recorded. Twenty-two of them returned one week later for a retesting, allowing for investigating temporal stability of individual FRN indices. Our results show that the FRN mainly reflects the additively integrated value of instant and delayed outcome consequences. Individual differences in the FRN sensitivity to the two consequence dimensions were specifically predictive for consequence-driven adjustments in choice behavior and moderately stable over time. Altogether, our findings are inconsistent with the idea that the FRN reflects a simple binary distinction between favorable and unfavorable action outcomes. Rather, the FRN appears to mirror a fine-grained scaling of action outcomes, which results from stable personal reward preferences and which is used for adjusting choice behavior. Given that the FRN is generated in the anterior midcingulate cortex, our study adds to recent literature according to which this structure uses multiple information to learn complex action-outcome values.

Background While the facilitatory and inhibitory effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) protocols have been well documented on motor physiology, the action of TBS protocols on prefrontal functioning remain unclear. Here we asked whether iTBS or cTBS can differentially modulate reward-related signaling in the anterior midcingulate cortex (aMCC). Methods Across 2 experiments, we used a robot-assisted transcranial magnetic stimulation system, combined with electroencephalogram recordings, to investigate the aftereffects of prefrontal iTBS and cTBS on the reward positivity, an electrophysiological signal believed to index sensitivity of the aMCC to rewards. Twenty adults (age, 18–28 years) participated in experiment 1 in which we used a scalp landmark for TBS targeting, and 14 adults (age, 18–28 years) participated in experiment 2, in which we aimed to increase TBS effectiveness by utilizing cortical thickness maps to select individualized dorsal lateral prefrontal cortex targets. Results We demonstrated that prefrontal iTBS suppressed reward-related signaling in the aMCC (reduction in reward positivity) and caused a decrease in postfeedback switch choices. cTBS displayed no effect. We replicated and strengthened this effect on the reward positivity by targeting dorsal lateral prefrontal cortex regions displaying maximal cortical thickness. Conclusions While these results are inconsistent with reported TBS effects on motor cortex, the present findings offer a novel transcranial magnetic stimulation targeting approach and normative insights into the magnitude and time course of TBS-induced changes in aMCC excitability. By modulating how the aMCC links value to goal-directed behavior, this research opens an exciting new era of investigative possibilities in the understanding of aMCC function and treatment of aMCC dysfunction.

Significance Across primates, a set of ventrolateral frontal (VLF) and dorsomedial frontal (DMF) brain areas are critical for voluntary vocalizations. Determining their individual roles in vocal control and how they might have changed is crucial to understanding how the complex vocal control in human speech emerged during primate brain evolution. The present work demonstrated key functional dissociations in Broca’s region of the VLF (i.e., between dorsal and ventral area 44, and area 45) and in the DMF (i.e., between the presupplementary motor area [pre-SMA] and the midcingulate cortex [MCC]) during the cognitive control of orofacial, nonspeech, and speech vocal responses., In the primate brain, a set of areas in the ventrolateral frontal (VLF) cortex and the dorsomedial frontal (DMF) cortex appear to control vocalizations. The basic role of this network in the human brain and how it may have evolved to enable complex speech remain unknown. In the present functional neuroimaging study of the human brain, a multidomain protocol was utilized to investigate the roles of the various areas that comprise the VLF–DMF network in learning rule-based cognitive selections between different types of motor actions: manual, orofacial, nonspeech vocal, and speech vocal actions. Ventrolateral area 44 (a key component of the Broca’s language production region in the human brain) is involved in the cognitive selection of orofacial, as well as, speech and nonspeech vocal responses; and the midcingulate cortex is involved in the analysis of speech and nonspeech vocal feedback driving adaptation of these responses. By contrast, the cognitive selection of speech vocal information requires this former network and the additional recruitment of area 45 and the presupplementary motor area. We propose that the basic function expressed by the VLF–DMF network is to exert cognitive control of orofacial and vocal acts and, in the language dominant hemisphere of the human brain, has been adapted to serve higher speech function. These results pave the way to understand the potential changes that could have occurred in this network across primate evolution to enable speech production.

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.

Background The ultra-high risk (UHR) paradigm allows the investigation of individuals at increased risk of developing psychotic or other mental disorders with the aim of making prevention and early intervention as specific as possible in terms of the individual outcome. Methods Single-session 1H-/31P-Chemical Shift Imaging of thalamus, prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices was applied to 69 UHR patients for psychosis and 61 matched healthy controls. N-acetylaspartate (NAA), glutamate/glutamine complex (Glx), energy (PCr, ATP) and phospholipid metabolites were assessed, analysed by ANOVA (or ANCOVA [with covariates]) and correlated with symptomatology (SCL-90R). Results The thalamus showed decreased NAA, inversely correlated with self-rated aggressiveness, as well as increased PCr, and altered phospholipid breakdown. While the aMCC showed a pattern of NAA decrease and PCr increase, the DLPFC showed PCr increase only in the close-to-psychosis patient subgroup. There were no specific findings in transition patients. Conclusion The results do not support the notion of a specific pre-psychotic neurometabolic pattern, but likely reflect correlates of an “at risk for mental disorders syndrome”. This includes disturbed neuronal (mitochondrial) metabolism in the thalamus and aMCC, with emphasis on left-sided structures, and altered PL remodeling across structures.

The discovery of a circuit from the midcingulate cortex to the posterior insula that is essential for cortical sensitization sheds light on the plasticity mechanisms responsible for the transition from acute to chronic pain.

The rabbit midcingulate cortex that enclosed four cortical areas was immunohistochemically studied using a calcium-binding protein, parvalbumin, as a neurochemical marker. The distribution of parvalbumin-immunopositive somata and fibres was similar across all four areas, where they were present mainly in layers 2/3 and 5. However, there were a slightly greater number of the immunopositive structures in the two ventral areas than the two dorsal areas. Similarity in the distribution of parvalbumin-immunopositive structures across the four areas suggests that neurons expressing parvalbumin may be involved in similar functions across the constituent areas of the rabbit midcingulate cortex.

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.

Situated medially and centrally in the brain, the anterior midcingulate cortex (aMCC) is a nexus of control. This specialized neocortical brain region participates in large-scale brain networks underlying attention, motor, and limbic processes. The functional diversity and proximity of cognitive and affective subdivisions within this region are its distinguishing features, rendering it an effective site for integration across domains. Here we review comparative neuroanatomic, meta-analytic, and connectomic analyses contributing to the emerging picture of the aMCC as comprising functionally diverse, flexible network nodes involved in multiple regulatory behaviors. We further present data providing evidence for an organizing gradient along the anterior and midcingulate cortex and explore the implications of these findings for understanding the functional role of the anterior midcingulate within this spectrum. We conclude by highlighting open questions and proposing future directions for investigations into the functional role of this important network convergence zone.

Spatial neglect is asymmetric attention, orienting, and action causing functional disability. It is linked to higher-order cortical sensory processing; however, spatial motor “Aiming” processing is critical to fundamental, adaptive environmental movement and daily life function. The cingulate cortex, in particular the anterior cingulate and anterior midcingulate cortex, is strongly linked to spatial Aiming deficits and likely to predict daily life disability in spatial neglect. The authors review the impact and mechanisms of spatial neglect and then describe specific symptoms associated with spatial neglect that are theoretically linked to cingulate cortical functions or associated with lesions extending to cingulate regions in a well-characterized spatial neglect cohort. The treatment implications for a link between cingulate cortex spatial Aiming neglect and therapies that improve spatial action, arousal, and persistence are discussed. Clinicians may want to consider theoretically motivated treatments targeted at specific symptoms as well as use treatments supported for spatial neglect based on unselected and uncharacterized groups.

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.

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.

The function of midcingulate cortex (MCC) remains elusive despite decades of investigation and debate. Complicating matters, individual MCC neurons respond to highly diverse task-related events, and MCC activation is reported in most human neuroimaging studies employing a wide variety of task manipulations. Here we investigate this issue by applying a model-based cognitive neuroscience approach involving neural network simulations, functional magnetic resonance imaging, and representational similarity analysis. We demonstrate that human MCC encodes distributed, dynamically evolving representations of extended, goal-directed action sequences. These representations are uniquely sensitive to the stage and identity of each sequence, indicating that MCC sustains contextual information necessary for discriminating between task states. These results suggest that standard univariate approaches for analyzing MCC function overlook the major portion of task-related information encoded by this brain area and point to promising new avenues for investigation.

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.

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.

BackgroundSocial anxiety disorder (SAD) is characterized by fear of social and performance situations. The consequence of scrutiny by others for the neural processing of performance feedback in SAD is unknown.MethodsWe used event-related functional magnetic resonance imaging to investigate brain activation to positive, negative, and uninformative performance feedback in patients diagnosed with SAD and age-, gender-, and education-matched healthy control subjects who performed a time estimation task during a social observation condition and a non-social control condition: while either being monitored or unmonitored by a body camera, subjects received performance feedback after performing a time estimation that they could not fully evaluate without external feedback.ResultsWe found that brain activation in ventral striatum (VS) and midcingulate cortex was modulated by an interaction of social context and feedback type. SAD patients showed a lack of social-context-dependent variation of feedback processing, while control participants showed an enhancement of brain responses specifically to positive feedback in VS during observation.ConclusionsThe present findings emphasize the importance of social-context processing in SAD by showing that scrutiny prevents appropriate reward-processing-related signatures in response to positive performances in SAD.

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

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.

A balanced integration of emotional and cognitive information is essential for flexible behaviour, which involves the anterior cingulate cortex (ACC) and the midcingulate cortex (MCC) [1]. Both clinical and preclinical researchers have been interested in studying the role of ACC and MCC in health and disease but preclinical rodent studies so far have suffered from a severe misconception: The definition of ACC/MCC used for rodents is not homologous to the human definition of ACC/MCC. Due to this, numerous findings of rodent studies are not directly translatable to the human situation, an issue that has been addressed in the past [2]. However, the majority of researchers still use the non-homologous definition of rodent ACC/MCC and awareness of the homologous nomenclature needs to be raised. Here, we demonstrate in a series of experiments the value of the homologous rodent ACC/MCC definition for translational research. We conducted a literature review, showing that the non-homologous definition of rodent ACC/MCC does not match human ACC/MCC anatomy and connectivity, while the homologous definition does. We then determined volumes of ACC and MCC in the BALB/cJ mouse, a model demonstrating characteristic symptoms of CD and ADHD (increased aggression and inattention). BALB/cJ mice were tested in the resident-intruder paradigm, demonstrating increased aggression (reduced attack latency: p 0.55 and all p 0.05), highlighting the importance of using the homologous ACC/MCC definition. Last, we aimed to validate our histological findings by using voxel-based morphometry (VBM) of structural magnetic resonance imaging (MRI) data to measure ACC/MCC volumes. BALB/cJ and BALB/cByJ mice were tested in the 5-choice serial reaction time task, a task probing attention. BALB/cJ mice showed a global attention deficit, indicated by an increased percentage of omissions compared to BALB/cByJ mice (p 0.25 and p

Fear of pain (FOP) can increase risk for chronic pain and disability but little is known about corresponding neural responses in anticipation of potential pain. In this study, more (10 women, 6 men) and less (7 women, 6 men) pain-fearful groups underwent whole-brain functional magnetic resonance imaging (fMRI) during anticipation of near pain-threshold stimulation. Groups did not differ in the proportion of stimuli judged to be painful but pain-fearful participants reported significantly more state fear prior to stimulus exposure. Within the entire sample, stronger activation was found in several pain perception regions (e.g., bilateral insula, midcingulate cortex (MCC), thalamus, superior frontal gyrus) and visual areas linked to decoding stimulus valences (inferior orbital cortex) during anticipation of "painful" stimuli. Between groups and correlation analyses indicated pain-fearful participants experienced comparatively more activity in regions implicated in evaluating potential threats and processing negative emotions during anticipation (i.e., MCC, mid occipital cortex, superior temporal pole), though group differences were not apparent in most so-called "pain matrix" regions. In sum, trait- and task-based FOP is associated with enhanced responsiveness in regions involved in threat processing and negative affect during anticipation of potentially painful stimulation.

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.

To describe the novel finding of epileptic spasms arising from a cingulate lesion.We describe two children presenting with epileptic spasms who had lesions of the cingulate gyrus on MRI.In both patients, the lesions involved the midcingulate cortex. Seizures were characterized by prominent motor manifestations and resembled spasms. Both patients had a complete resolution of seizures after resection of their cingulate lesions.Cingulate seizures can present with a variety of behaviors including complex motor manifestations, vocalizations, and autonomic changes. Lesions in the midcingulate cortex can also produce epileptic spasms.

Many structural brain asymmetries accompany left hemisphere language dominance. For example, the cingulate sulcus is larger in the medial cortex of the right hemisphere, while the more dorsal paracingulate sulcus is larger on the left. The functional significance of these asymmetries is unknown because fMRI studies rarely attempt to localize activation to specific sulci, possibly due to difficulties in consistent sulcal identification. In medial cortex, for example, there are many regions of partial sulcal overlap where MRI images do not provide sufficient information to unambiguously distinguish a paracingulate sulcus from a displaced anterior cingulate segment. As large samples of postmortem material are rarely available for cytoarchitectural studies of sulcal variation, we have investigated the effect of variation in boundary and sulcal definition on paracingulate asymmetry in the MRI scans of 200 healthy adults (100 men, 100 women). Although women displayed a reliable asymmetry in the size of the paracingulate sulcus, regardless of boundary definition or technique, asymmetry was greatest when (1) the measurement was limited to the midcingulate region between the genu and the anterior commissure; and (2) the more dorsal of two overlapping sulci was always classified as a paracingulate sulcus (rather than as a displaced cingulate segment). The fact that paracingulate asymmetry is maximal in the midcingulate region suggests that this region may play a particular role in hemispheric specialization for language. Future work should investigate the structural and functional correlates of sulcal variation in this region.

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.

This article presents a selective review of recent developments in research on hypnotic pain reduction. A profusion of well-controlled studies of hypnotic analgesia in children suggests that hypnosis ranks among the more effective psychological tools for managing the distress experienced by youngsters undergoing invasive medical procedures. This literature also draws attention to the importance of matching interventions to natural pain coping strategies. Virtual reality hypnosis shows much promise as a treatment and may offer hope to people who might otherwise be unable to experience hypnotic analgesia. Response expectancies appear to be a key psychological mechanism of hypnotic pain reduction. Neuroimaging studies point to activity in the midcingulate cortex as a possible biological mechanism of hypnotic analgesia. More generally, based upon the findings of a sound empirical literature, important meta-analytic and qualitative reviews have concluded that hypnosis is effective for reducing both experimental and clinical pain. Indeed, the study of hypnotic pain reduction is vigorous, innovative, and may well have entered a golden era of research. Copyright © 2008 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.

This chapter assesses cingulate cortex from four perspectives: (1) Regional, areal and cellular organization with special emphasis given to midcingulate cortex (MCC) as it is a relatively new entrant to rodent research; (2) Autonomic, thalamic and cortical connections of anterior cingulate cortex (ACC); (3) Anterior cingulate pain architecture in terms of thalamic afferents, intracortical processing and regulation by μ-opioid receptors, and output systems including descending inhibitory and facilatory control mechanisms; and (4) Comparative organization of rat and human cingulate cortices. Throughout the chapter there are a number of overarching themes such as differentiation of ACC and MCC with cytological, connection and ligand binding methods. Although MCC has never been studied behaviorally, a new theory of its functions is presented to guide future research efforts. Finally, the cumulative outcome of this review is a new rat flat map that includes dorsal and ventral area 32, MCC areas 24a′ and 24b′, and anterior and posterior divisions of retrosplenial areas 29 and 30. This comprehensive map provides the basis for explicit comparative neuroanatomical studies and will be of particular value in devising rodent models of human cingulate diseases.

Twenty-five youth with attention-deficit/hyperactivity disorder (ADHD) were scanned with functional magnetic resonance imaging (fMRI) while performing a Go/No-go task before and after 6–8 weeks of randomized once-daily treatment with either the α2A-adrenergic receptor agonist guanfacine or placebo. Clinical improvement was greater for guanfacine than placebo and was differentially associated with reduced activation for guanfacine compared with placebo in the right midcingulate cortex/supplementary motor area and the left posterior cingulate cortex.

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.

SummaryAnterior cingulate cortex (ACC) is known to be involved in functions such as emotion, pain, and cognitive control. While studies in humans and nonhuman mammals have advanced our understanding of ACC function, the subjective correlates of ACC activity have remained largely unexplored. In the current study, we show that electrical charge delivery in the anterior midcingulate cortex (aMCC) elicits autonomic changes and the expectation of an imminent challenge coupled with a determined attitude to overcome it. Seed-based, resting-state connectivity analysis revealed that the site of stimulation in both patients was at the core of a large-scale distributed network linking aMCC to the frontoinsular and frontopolar as well as some subcortical regions. This report provides compelling, first-person accounts of electrical stimulation of this brain network and suggests its possible involvement in psychopathological conditions that are characterized by a reduced capacity to endure psychological or physical distress.

Information processing in the medial frontal cortex is often said to be modulated in pathological conditions or by individual traits. This has been observed in neuroimaging and event-related potential studies centered in particular on midcingulate cortex (MCC) functions. This region of the brain is characterized by considerable intersubject morphological variability. Whereas in a subset of hemispheres only a single cingulate sulcus (cgs) is present, a majority of hemispheres exhibit an additional sulcus referred to as the paracingulate sulcus (pcgs). The present functional magnetic resonance imaging study defined the relationship between the local morphology of the cingulate/paracingulate sulcal complex and feedback-related activity. Human subjects performed a trial-and-error learning task in which they had to discover which one of a set of abstract stimuli was the best option. Feedback was provided by means of fruit juice, as in studies with monkeys. A subject-by-subject analysis revealed that the feedback-related activity during exploration was systematically located in the cgs when no pcgs was observed, but in the pcgs when the latter sulcus was present. The activations had the same functional signature when located in either the cgs or in the pcgs, confirming that both regions were homologues. Together, the results show that the location of feedback-related MCC activity can be predicted from morphological features of the cingulate/paracingulate complex.

Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well-understood. Here, it is asked whether neurofeedback success of frontal-midline (fm) theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior, and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one's own brain activity.

Neurobiological models of obsessive-compulsive disorder (OCD) assume abnormalities in corticostriatal networks involving cingulate and orbitofrontal cortices, but the connectivity within these systems is rarely addressed in experimental imaging studies in this patient group. Using an established monetary reinforcement paradigm known to involve the cingulate cortex and the ventral striatum, the present study sought to test for altered corticostriatal coupling in OCD patients anticipating potential punishment. The anterior midcingulate cortex (aMCC), a region integrating negative emotion, pain, and cognitive control, was chosen as a seed region due to its particular relevance in OCD, representing the neurosurgical target for cingulotomy, and showing increased responses to errors in OCD patients. Results from psychophysiological interaction analyses revealed that significantly altered, inverse coupling occurs between the aMCC and the ventral striatum when OCD patients anticipate potential punishment. This abnormality links the two major contemporary neurosurgical OCD target sites, and provides direct experimental evidence of altered corticostriatal connectivity in OCD. Noteworthy, an abnormal aMCC coupling with cortical areas outside of traditional corticostriatal circuitry was identified besides the alteration in the cingulostriatal pathway. In conclusion, these findings support the importance of applying connectivity methods to study corticostriatal networks in OCD, and favor the application of effective connectivity methods to study corticostriatal abnormalities in OCD patients performing tasks that involve symptom provocation and reinforcement learning.

Contains fulltext : 102927.pdf (Publisher’s version ) (Open Access) According to recent accounts, the processing of errors and generally infrequent, surprising (novel) events share a common neuroanatomical substrate. Direct empirical evidence for this common processing network in humans is, however, scarce. To test this hypothesis, we administered a hybrid error-monitoring/novelty-oddball task in which the frequency of novel, surprising trials was dynamically matched to the frequency of errors. Using scalp electroencephalographic recordings and event-related functional magnetic resonance imaging (fMRI), we compared neural responses to errors with neural responses to novel events. In Experiment 1, independent component analysis of scalp ERP data revealed a common neural generator implicated in the generation of both the error-related negativity (ERN) and the novelty-related frontocentral N2. In Experiment 2, this pattern was confirmed by a conjunction analysis of event-related fMRI, which showed significantly elevated BOLD activity following both types of trials in the posterior medial frontal cortex, including the anterior midcingulate cortex (aMCC), the neuronal generator of the ERN. Together, these findings provide direct evidence of a common neural system underlying the processing of errors and novel events. This appears to be at odds with prominent theories of the ERN and aMCC. In particular, the reinforcement learning theory of the ERN may need to be modified because it may not suffice as a fully integrative model of aMCC function. Whenever course and outcome of an action violates expectancies (not necessarily related to reward), the aMCC seems to be engaged in evaluating the necessity of behavioral adaptation. 10 p.

The midcingulate cortex and therefore the underlying midcingulum bundle (MCB) as well play a major role in attention. Although a specific structure's function does strongly depend on its neuroanatomical characteristics, research assessing the morphological variability of the midcingulate region is rather sparse. The present study examined the micro‐ and macrostructure of the MCB in both hemispheres by means of diffusion‐tensor imaging. Besides, effects of gender (Female = 40, Male = 39) and handedness (Lefthanders = 45, Righthanders = 34) were assessed as well. Measures of fractional anisotropy, mean diffusion, as well as the white matter volumes of the MCBs were assessed. By integration of multi‐modal images, the MCB was isolated and confounding with callosal fibers was avoided. Evidence was found indicating differences between hemispheres and gender regarding both volume and microstructural characteristics of the MCB. Interestingly, gender‐related effects seem to be substantially associated with variations in individual brain volumes. Handedness did not emerge as relevant factor in the analyses. These findings might indicate a higher functional connectivity of the left MCB and in males as compared to females. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.

Human dorsal midcingulate cortex (MCC) is activated during many cognitive tasks and its role in skeletomotor functions is reflected in the size, density, and neurofilament proteins (NFP) expressed by neurons in this region. The present study used antibodies for neuron-specific nuclear binding protein and NFP in three postmortem cases to assess the cytology of the dorsal midcingulate areas 24c′, 24d, and 32′ and supplementary motor cortex. Area 24c′ has a thin layer Va and a Vb with large and NFP+ neurons not present on the gyral surface. Area 24d has two divisions; area 24dv on the ventral bank has layer Vb neurons that form aggregates, while area 24dd on the dorsal bank has large and solitary layer Vb pyramids. Co-registration of each case to standardized coordinates showed that the rostral area 24d border is at the vertical plane of the anterior commissure and its caudal border with area 23c is −2±0.21 cm in the y-axis. The transition to supplementary motor areas is characterized by significant increases in the density of large, NFP expressing neurons in layer IIIc and a substantial reduction in the size and density of such neurons in layer V. Since many acute pain studies activate dorsal MCC, understanding the architecture of this region will help explain its selective vulnerability to chronic pain and stress syndromes.

Cognitive control is needed when mistakes have consequences, especially when such consequences are potentially harmful. However, little is known about how the aversive consequences of deficient control affect behavior. To address this issue, participants performed a two-choice response time task where error commissions were expected to be punished by electric shocks during certain blocks. By manipulating (1) the perceived punishment risk (no, low, high) associated with error commissions, and (2) response conflict (low, high), we showed that motivation to avoid punishment enhanced performance during high response conflict. As a novel index of the processes enabling successful cognitive control under threat, we explored electromyographic activity in the corrugator supercilii (cEMG) muscle of the upper face. The corrugator supercilii is partially controlled by the anterior midcingulate cortex (aMCC) which is sensitive to negative affect, pain and cognitive control. As hypothesized, the cEMG exhibited several key similarities with the core temporal and functional characteristics of the Error-Related Negativity (ERN) ERP component, the hallmark index of cognitive control elicited by performance errors, and which has been linked to the aMCC. The cEMG was amplified within 100 ms of error commissions (the same time-window as the ERN), particularly during the high punishment risk condition where errors would be most aversive. Furthermore, similar to the ERN, the magnitude of error cEMG predicted post-error response time slowing. Our results suggest that cEMG activity can serve as an index of avoidance motivated control, which is instrumental to adaptive cognitive control when consequences are potentially harmful.