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Anterior cingulate cortex

The anterior cingulate cortex (ACC) is a subdivision of the cingulate gyrus, a fold of cortical tissue located on the medial surface of the frontal lobe that encircles the corpus callosum, serving as a critical hub in the limbic system for integrating emotional, cognitive, and motor processes.^[1] It comprises Brodmann areas 24, 25, 32, and 33, and is anatomically bounded by the cingulate sulcus superiorly and the callosal sulcus inferiorly, connecting to regions such as the prefrontal cortex, orbitofrontal cortex, amygdala, thalamus, and motor areas to facilitate adaptive behavior.^[1] Embryologically derived from the telencephalon around the sixth week of gestation, the ACC matures functionally in stages, with motor and cognitive aspects developing in early childhood and social-emotional functions extending into adolescence.^[1] The ACC is functionally heterogeneous, often subdivided into the perigenual ACC (pACC), which primarily handles emotional processing and autonomic responses; the dorsal ACC (dACC), involved in cognitive control, reward-based decision-making, and conflict monitoring; and the midcingulate motor areas, which translate intentions into actions.^[1] In emotion regulation, the ACC receives inputs from the orbitofrontal cortex and amygdala regarding rewards and punishments, enabling the evaluation of emotional salience and guiding responses to stimuli like pleasure or pain.^[2] For instance, functional imaging studies show activation in the pregenual ACC during exposure to pleasant stimuli and in supracallosal regions for unpleasant ones, underscoring its role in affective awareness.^[2] Cognitively, the ACC supports motivation, goal-directed behavior, error detection, and inhibitory control by linking reward values to action outcomes, as evidenced by neuronal recordings in primates that encode effort and value during decision-making tasks.^[3] It also contributes to social cognition, including theory of mind and empathy, through connections with the prefrontal cortex and hippocampus, which aid in processing social cues and episodic memory relevant to interpersonal interactions.^[4] Lesions or dysfunction in the ACC, as seen in conditions like depression or schizophrenia, impair these functions, leading to deficits in initiation, volition, and adaptive responding.^[3] Overall, the ACC's evolutionary adaptations, such as the presence of spindle-shaped von Economo neurons found in humans, great apes, and other socially complex mammals such as cetaceans and elephants, highlight its expanded role in complex, flexible behaviors.^[5]

Anatomy

Location and Gross Structure

The anterior cingulate cortex (ACC) is located on the medial aspect of the frontal lobe, forming the anterior portion of the cingulate gyrus that arches over the genu and body of the corpus callosum. It resides on the medial surface of each cerebral hemisphere, superior to the corpus callosum and separated from it by the callosal sulcus. The cingulate sulcus runs parallel and superior to the callosal sulcus, demarcating the ACC from the superior frontal gyrus.^[1]^[6] The ACC spans Brodmann areas 24 (dorsal portion), 25 (subcallosal portion), 32 (rostral portion), and 33 (subgenual portion). Its gross boundaries are defined by the cingulate sulcus superiorly and the paracingulate sulcus, when present, which parallels the cingulate sulcus dorsally and contributes to individual variability in surface morphology. The paracingulate sulcus appears in approximately 50% of individuals, more prominently on the left hemisphere, influencing the overall contour and prominence of the region. In adults, the bilateral volume of the ACC is approximately 5-7 cm³, reflecting its compact yet pivotal positioning within the limbic system.^[1]^[6]^[7]^[8] Evolutionarily, the ACC has expanded in humans relative to other primates, correlating with increased encephalization and the emergence of specialized spindle-shaped von Economo neurons in layer Vb, which are found in humans, great apes, cetaceans, and elephants, but are absent in most other primate species and linked to heightened cognitive processing demands. This expansion underscores the region's adaptation for complex integration in human brain architecture.^[9]^[5]

Subregions and Cytoarchitecture

The anterior cingulate cortex (ACC) is parcellated into distinct subregions based on cytoarchitectonic criteria, with the dorsal ACC (dACC) primarily encompassing Brodmann area 24 and the rostral/ventral ACC (rACC/vACC) including areas 25, 32, and 33. The dACC features a more differentiated laminar organization suited to cognitive demands, while the rACC/vACC shows variations that align with affective processing, such as in the subgenual zone (areas 25 and s32).^[10] These divisions arise from differences in cell packing, layer widths, and neuronal morphology along the dorsoventral axis.^[11] Cytoarchitecturally, the ACC belongs to the limbic cortex, exhibiting predominantly agranular (e.g., area 25, lacking a distinct layer IV) and dysgranular (e.g., area 32, with a rudimentary layer IV) patterns that distinguish it from isocortical regions.^[12] Layers II and III are often broad and neuron-dense in ventral portions, with layer V containing large pyramidal projection neurons critical for output signaling.^[10] In the rACC, layer Vb is particularly notable for hosting von Economo neurons (VENs), which are large, spindle-shaped bipolar cells found in humans, great apes, cetaceans, and elephants, enabling rapid interregional communication.^[13]^[5] These VENs comprise approximately 1-2% of neurons in layer V of the ACC, with densities averaging around 56 VENs per mm³ in healthy adults.^[14]^[15] Histological variations further delineate subregions: the dACC displays denser packing and more neurofilament-rich neurons in layer Va, supporting complex processing, whereas the subgenual vACC has thinner layer III, broader layer II, and smaller neurons with shorter dendrites, adaptations linked to emotional roles.^[10] The pregenual dACC (pd24c) shows aggregates of neurons in layer Vb and broader layer II compared to its ventral counterpart (pv24c), highlighting gradient-like transitions in cellular architecture.^[10]

Connectivity

The anterior cingulate cortex (ACC) receives a variety of afferent inputs that integrate sensory, emotional, and cognitive information. Prominent inputs arise from the mediodorsal nucleus of the thalamus, which provides relays for cognitive and executive signals, particularly influencing the dorsal ACC (dACC). The amygdala sends projections conveying emotional and fear-related information, with stronger connections to the rostral ACC (rACC) and subgenual ACC (sACC).^[16] Additionally, the insula contributes interoceptive signals related to visceral sensations and pain, linking primarily to the rACC for affective processing. Efferent outputs from the ACC project to regions involved in executive control, reward evaluation, and pain modulation. The ACC sends projections to the lateral prefrontal cortex (PFC), facilitating cognitive control and decision-making, with dACC outputs being particularly prominent to dorsolateral PFC areas. Outputs to the orbitofrontal cortex (OFC) support reward processing and valuation, originating mainly from rACC subregions.^[16] For pain regulation, ACC efferents contribute to descending pathways that modulate nociceptive transmission in the spinal cord dorsal horn, often via intermediate structures like the periaqueductal gray and rostral ventromedial medulla. Key white matter tracts underpin ACC interconnectivity. The cingulum bundle serves as a major pathway for intra-cingulate communication, linking ACC subregions with posterior cingulate areas and facilitating exchanges with prefrontal and parietal cortices, as well as thalamic nuclei. The uncinate fasciculus connects the ACC to the temporal lobe, including the amygdala and hippocampus, supporting emotional and memory-related integrations. Subregional differences in connectivity reflect functional specialization. The dACC exhibits stronger links to executive networks, such as the frontoparietal control system, via projections to lateral PFC and supplementary motor areas. In contrast, the rACC connects more extensively to limbic structures, including the hypothalamus for autonomic responses and the ventral striatum for motivation.^[16] These patterns, conserved across species, enable the ACC to bridge cognitive and emotional domains.^[17]

Functions

Cognitive Control and Monitoring

The anterior cingulate cortex (ACC), particularly its dorsal subdivision (dACC), plays a central role in cognitive control by detecting and signaling conflicts in information processing, thereby enabling adaptive adjustments in attention and executive function. According to the conflict monitoring theory, the dACC identifies mismatches between competing response options, such as when multiple stimuli evoke incompatible actions, prompting recruitment of prefrontal resources to resolve the interference. This function is evident in tasks requiring selective attention, where the dACC activation scales with the degree of response competition, facilitating top-down control to suppress irrelevant information and prioritize goal-relevant responses.^[18] A key example of this monitoring process occurs in the Stroop task, where incongruent color-word stimuli (e.g., the word "red" printed in blue ink) elicit heightened dACC activity compared to congruent trials, reflecting detection of the conflict between reading the word and naming the color. Functional magnetic resonance imaging (fMRI) studies consistently show dACC hyperactivity during high-conflict trials across various paradigms, correlating with subsequent behavioral adjustments like slower response times to enhance accuracy. In the Eriksen flanker task, where central targets are flanked by compatible or incompatible distractors, dACC engagement signals the need for increased attentional control, particularly on incongruent trials that demand suppression of flanker interference.^[19] Error detection represents another core aspect of ACC-mediated monitoring, manifesting as the error-related negativity (ERN), an event-related potential component observed in electroencephalography (EEG) approximately 50-100 ms after an erroneous response, with a peak negativity at 200-300 ms post-error. The dACC is implicated as a primary generator of the ERN, which reflects rapid evaluation of performance discrepancies and initiates compensatory mechanisms to improve future accuracy.^[20] Lesion studies in humans with anterior cingulate damage demonstrate impaired error awareness and reduced post-error slowing, underscoring the region's necessity for online performance monitoring. The ACC also contributes to task-switching by detecting the need for cognitive set reconfiguration, as seen in paradigms requiring alternation between rules or response mappings.^[21] During switches, dACC activity predicts enhanced prefrontal engagement and behavioral adaptation, such as reduced perseveration on prior tasks.^[22] Patients with ACC lesions exhibit deficits in set-shifting, including prolonged latencies and increased errors on Wisconsin Card Sorting Test-like tasks, confirming the region's role in overcoming inertial biases toward outdated strategies. The rostral anterior cingulate cortex (rACC) is pivotal in emotion regulation, particularly through its capacity to downregulate amygdala responses during cognitive reappraisal. In reappraisal tasks, where individuals reinterpret emotionally evocative stimuli to lessen their impact, rACC activation increases and negatively correlates with amygdala activity, leading to reduced negative affect and enhanced emotional control. This top-down modulation resolves emotional conflicts by inhibiting limbic reactivity, as demonstrated in functional neuroimaging studies. In social evaluation, the anterior cingulate cortex (ACC) facilitates empathy and the processing of social exclusion. Activation in the ACC occurs when individuals observe pain in others, engaging the affective components of empathy without necessarily recruiting sensory pain networks, thereby enabling vicarious emotional sharing.^[23] Likewise, during the Cyberball paradigm—a virtual ball-tossing game simulating social rejection—ACC engagement correlates with self-reported distress, highlighting its role in detecting and responding to interpersonal ostracism.^[24] Dysfunction in the rACC contributes to impaired maternal bonding in postpartum depression (PPD). In PPD, increased functional connectivity involving the subgenual ACC—a subregion of the rACC—reflects aberrant hyperactivity that sustains negative rumination and blunts reward responses to infant cues, thereby disrupting attachment formation and maternal sensitivity.^[25] The ACC also underpins interpersonal conflict resolution by signaling inequity aversion in social exchanges. In the ultimatum game, where participants decide whether to accept or reject resource divisions, unfair offers provoke ACC activation, which predicts rejection behavior and underscores the region's involvement in fairness judgments and social norm enforcement.

Reward Learning and Decision-Making

The anterior cingulate cortex (ACC) plays a pivotal role in reward-based learning by implementing prediction error signaling through interactions with dopaminergic systems, which facilitate the updating of value representations for actions and outcomes. Dopaminergic neurons in the midbrain project to the ACC, conveying reward prediction errors (RPEs) that highlight discrepancies between expected and actual rewards, thereby driving associative learning and behavioral adaptation.^[26] This interaction enables the ACC to integrate sensory cues with reward history, refining internal models of environmental contingencies to optimize future choices. Seminal electrophysiological studies in primates have demonstrated that ACC neurons respond to these dopaminergic signals, encoding errors that promote learning from both rewarding and non-rewarding experiences without strictly mirroring the signed nature of midbrain dopamine responses.^[27] In decision-making processes, the ACC integrates costs and benefits, particularly in foraging tasks where individuals must evaluate resource patches under uncertainty. For instance, in patch-foraging paradigms, ACC activity signals the relative value of continuing exploitation versus switching to exploration, balancing immediate gains against potential future rewards. Recent human intracranial recordings have revealed that beta oscillations (12-30 Hz) in the ACC predict reward biases, with increased beta power preceding choices toward higher-value options and correlating with the magnitude of behavioral preference shifts.^[28] These oscillations also track actual reward receipt, underscoring the ACC's role in dynamically adjusting decision thresholds based on integrated cost-benefit evaluations.^[29] The ACC supports the exploration-exploitation trade-off in adaptive reinforcement learning, particularly through loops with the striatum that optimize behavior in uncertain environments. In tasks requiring flexibility between persistent exploitation of known rewards and exploratory sampling of alternatives, ACC-striatal circuits causally modulate the balance, enhancing exploration during periods of low certainty to maximize long-term gains.^[30] During feedback processing, the ACC encodes signed prediction errors in probabilistic tasks, differentiating between positive and negative deviations from expectations to guide value updates. For example, in reversal learning paradigms with variable reward probabilities, ACC neurons signal positive errors (e.g., +0.5 for an unexpected gain when expecting a 50% chance) by increasing activity to reinforce successful actions, while negative errors prompt strategy adjustments. This signed encoding, observed via single-unit recordings, distinguishes the ACC from regions like the ventral striatum, which may prioritize unsigned surprise, and contributes to precise error-driven learning without overgeneralizing to mere novelty detection.^[31]

Pain and Sensory Integration

The anterior cingulate cortex (ACC), particularly its rostral subdivision (rACC), plays a central role in processing the affective dimension of pain, encoding the unpleasantness and emotional distress associated with nociceptive stimuli rather than the sensory-discriminative aspects such as intensity or location, which are primarily handled by the insula and somatosensory cortices.^[32]^[33] Functional neuroimaging studies have demonstrated that rACC activation correlates specifically with subjective ratings of pain unpleasantness during acute noxious stimulation, supporting its involvement in the motivational and emotional evaluation of pain.^[34] This affective processing facilitates adaptive behavioral responses, such as avoidance or seeking relief, by integrating nociceptive inputs with cognitive and emotional contexts.^[35] In chronic pain conditions, the ACC exhibits sustained hyperactivity that contributes to central sensitization, a state of heightened neural responsiveness amplifying pain perception.^[36] Recent studies have identified synaptic potentiation mechanisms in the ACC, including long-term potentiation (LTP) of glutamatergic synapses, as key drivers of this hypersensitivity; for instance, 2024 research using rodent models of neuropathic and visceral pain showed that LTP in ACC pyramidal neurons sustains hyperalgesia by enhancing excitatory transmission and behavioral pain responses.^[37] This potentiation is mediated by calcium-permeable AMPA receptors and involves signaling pathways like ERK and CaMKIV, leading to persistent amplification of pain signals even after the initial injury resolves.^[38] Such changes underscore the ACC's role in the transition from acute to chronic pain states, where maladaptive plasticity perpetuates emotional suffering and functional impairment.^[39] The ACC integrates diverse pain signals, combining visceral nociception—such as from gastrointestinal or cardiac sources—with other aversive experiences through shared neural pathways.^[40] For example, visceral pain activates ACC circuits that overlap with those processing social pain, like rejection or exclusion, enabling a unified affective response to both physical and interpersonal threats; this convergence is evident in meta-analyses showing consistent ACC engagement across these domains.^[41] These integrative functions allow the ACC to contextualize pain within broader emotional and social frameworks, influencing empathy and interpersonal behaviors.^[33] Furthermore, the ACC contributes to descending pain modulation by projecting to the periaqueductal gray (PAG), a midbrain structure that gates nociceptive transmission at the spinal level.^[42] These projections, primarily from the dorsal ACC, release neurotransmitters like glutamate to activate PAG neurons, thereby inhibiting ascending pain signals and dampening spinal nociception during adaptive antinociceptive responses.^[43] In chronic pain, however, dysregulated ACC-PAG signaling can shift toward facilitation, exacerbating hyperalgesia and fear-avoidance behaviors.^[44]

Development and Plasticity

Prenatal and Postnatal Development

The anterior cingulate cortex (ACC) originates early in human gestation as part of the limbic system's foundational structures. The cingulate cortex begins to form around the 8th week of gestation, coinciding with the initial differentiation of neuroblasts in the telencephalon.^[45] Around gestational weeks 24 to 28, the cingulate sulcus emerges as one of the primary sulci, delineating the region's gross morphology.^[46] Brodmann area 24 (BA24), the primary cytoarchitectonic subdivision of the ACC, differentiates during the second trimester, as neuronal migration and layering establish its distinct granular and dysgranular characteristics.^[47] Initial thalamocortical projections to the ACC arrive by the late second trimester, around week 26, initiating basic sensory-relay pathways that support emerging thalamo-cingulate interactions.^[47] Postnatally, the ACC exhibits rapid structural refinement, with myelination accelerating in the first two years of life to enhance signal efficiency across its connections. White matter tracts in the cingulate region, including those linking to prefrontal and limbic areas, show substantial increases in myelin density during this period, aligning with rapid overall brain growth rates of up to 1% per day in early infancy.^[47] The dorsal ACC (dACC), involved in cognitive monitoring, shows enhanced error-related activation patterns by age 10, though full functional maturity continues into adolescence, as evidenced by stabilized cortical thickness. In contrast, the rostral ACC (rACC), associated with emotional processing, undergoes prolonged maturation extending into early adulthood, peaking around ages 25 to 30, with continued thinning and connectivity refinements observed through the third decade.^[48] Adolescence represents a critical period for ACC development, characterized by changes in regional volume driven by pubertal hormones such as testosterone and estradiol that influence gray matter expansion and synaptic reorganization. This hormonal modulation heightens the ACC's vulnerability to early life stress, which can disrupt volumetric trajectories and long-term adaptability. Functional connectivity within ACC networks strengthens progressively from infancy, with postnatal refinements enabling the emergence of basic cognitive control mechanisms by age 7, as task-related activations in error monitoring and attention shift become more robust.^[49]

Synaptic Plasticity and Adaptability

The anterior cingulate cortex (ACC) exhibits robust synaptic plasticity, particularly through long-term potentiation (LTP), a process critical for encoding persistent neural changes underlying behaviors such as pain memory. LTP in the ACC is primarily mediated by N-methyl-D-aspartate (NMDA) receptors, where activation leads to calcium influx and subsequent enhancement of synaptic efficacy, contributing to the strengthening of pain-related signals even after the initial stimulus subsides.^[36]^[50] This NMDA-dependent LTP involves correlated pre- and postsynaptic activity driving synaptic strengthening.^[36] Adult neurogenesis in the ACC is limited but supports hippocampal-like processes, facilitating neural adaptability in response to environmental demands. A 2023 review highlights that the ACC orchestrates adult neurogenesis through connections to subventricular and subgranular zones, promoting neuron generation that aids memory consolidation under stress conditions, such as chronic emotional or cognitive strain.^[51] This neurogenesis enhances circuit flexibility, allowing the ACC to integrate stress-induced changes into long-term adaptive responses. Experience-dependent remodeling in the ACC enables dynamic neural adaptability, exemplified by mechanisms sustaining chronic pain. Recent 2024 studies demonstrate that synchronized oscillating electromagnetic fields generated in the ACC's layer 2/3 pyramidal neurons contribute to pain chronicity by amplifying synaptic sensitization and integrating inputs from thalamic and limbic regions, thus perpetuating aversive states through experience-driven plasticity.^[37] At the molecular level, brain-derived neurotrophic factor (BDNF) upregulation in the ACC drives dendritic spine growth, supporting learning-induced structural changes. BDNF signaling enhances spine density and maturation on pyramidal neurons, promoting synaptic connectivity and plasticity in response to behavioral experiences like reward or aversive learning.^[52]^[53]

Research Methods

Neuroimaging Techniques

Neuroimaging techniques have revolutionized the study of the anterior cingulate cortex (ACC) by providing non-invasive methods to map its structure, connectivity, and functional activity in vivo. These approaches, including functional magnetic resonance imaging (fMRI), structural MRI, and diffusion tensor imaging (DTI), offer complementary insights into ACC involvement in cognitive and emotional processes, with spatial resolutions enabling subregional differentiation between dorsal (dACC) and rostral (rACC) areas.^[54] Functional MRI, particularly through blood-oxygen-level-dependent (BOLD) contrast, is a primary tool for detecting ACC activation during tasks requiring cognitive control, such as conflict monitoring. With typical spatial resolutions of 2-3 mm, fMRI localizes BOLD signals to the dACC in paradigms like the Stroop task, where incongruent stimuli elicit significant activation reflecting response conflict detection.^[55] Seminal studies demonstrate robust dACC engagement in these tasks, with BOLD responses scaling to conflict intensity and predicting subsequent behavioral adjustments.^[56] Structural MRI facilitates volumetric assessment of the ACC, quantifying gray matter integrity and revealing atrophy in neuropsychiatric conditions. In major depressive disorder, volumetric analyses show significant ACC volume reductions, particularly in the subgenual region, correlating with symptom severity and treatment response.^[57] These findings highlight structural MRI's role in identifying morphological changes that underlie ACC dysfunction.^[58] Diffusion tensor imaging (DTI) evaluates white matter integrity connecting the ACC via tracts like the cingulum bundle, using metrics such as fractional anisotropy (FA) to assess fiber coherence. In healthy adults, higher FA values indicate robust directional connectivity between the ACC and prefrontal or temporal regions.^[59] Deviations in FA signal potential disruptions in ACC-related networks.^[60] Recent advances in resting-state fMRI have elucidated intrinsic functional connectivity patterns involving the ACC, linking stronger rACC-dorsolateral prefrontal cortex (dlPFC) coupling to psychological resilience in 2024 studies.^[61] These connectivity analyses, often using seed-based approaches, complement task-based methods by revealing baseline network dynamics associated with adaptive cognition.^[62]

Electrophysiological Approaches

Electroencephalography (EEG) and event-related potentials (ERPs) provide high temporal resolution for capturing real-time activity in the anterior cingulate cortex (ACC), particularly in relation to error processing and feedback evaluation. The error-related negativity (ERN), a prominent ERP component, manifests as a negative deflection peaking approximately 50 ms after an erroneous response, with typical amplitudes ranging from -5 to -10 μV, and is maximal at the frontocentral FCz electrode, reflecting ACC involvement in performance monitoring.^[63] Similarly, the feedback-related negativity (FRN), observed around 250-300 ms post-feedback, is larger for negative outcomes and also peaks at FCz, indicating ACC sensitivity to outcome valence in decision contexts.^[64] These components offer millisecond-precision insights into conflict signals, such as those arising during cognitive control tasks.^[65] Intracranial recordings enable direct measurement of ACC neural activity with superior spatial specificity compared to scalp methods. In primate studies, single-unit recordings reveal that ACC neurons exhibit increased firing rates 100-200 ms prior to error commission, signaling anticipatory error processing during tasks requiring response selection.^[66] Recent human intracranial EEG (iEEG) findings from 2024 demonstrate beta-band (12-30 Hz) desynchronization in the ACC during value-based decision-making, where reduced beta power correlates with reward prediction and choice biases, highlighting the region's role in integrating motivational signals.^[67] Magnetoencephalography (MEG) complements EEG by detecting magnetic fields from ACC dipoles, particularly during conflict resolution, with evoked amplitudes typically in the 50-100 fT range. MEG source modeling localizes conflict-related activity to the ACC, capturing oscillatory dynamics such as theta-band increases around 200-300 ms post-stimulus in tasks involving response competition.^[68] In animal models, optogenetic techniques have established the ACC's causal contributions to exploratory behavior in rodents. A 2024 study using optogenetic inhibition of ACC neurons in rats during decision tasks showed impaired initiation and flexibility in exploration-exploitation trade-offs, confirming the region's necessity for adaptive behavioral adjustments under uncertainty.^[69]

Pathology

Psychiatric Disorders

In obsessive-compulsive disorder (OCD), the dorsal anterior cingulate cortex (dACC) exhibits hyperactivation during error monitoring tasks, as evidenced by functional magnetic resonance imaging (fMRI) studies showing increased blood-oxygen-level-dependent (BOLD) signals in response to conflict and errors.^[70] This hyperactivity, often quantified as elevated BOLD responses compared to healthy controls, reflects impaired cognitive control and excessive error signaling in OCD pathophysiology.^[71] Surgical interventions like cingulotomy, which target the ACC, have demonstrated symptom reduction in 35-70% of treatment-refractory cases, with Yale-Brown Obsessive Compulsive Scale scores decreasing by at least 35% in responders.^[72] In major depressive disorder, hypoactivity in the rostral anterior cingulate cortex (rACC) correlates with anhedonia, a core symptom involving diminished reward responsiveness and emotional blunting.^[73] This reduced rACC engagement during emotional processing tasks underscores its role in affective regulation deficits. A 2023 study of deep brain stimulation (DBS) targeting the subgenual ACC in 10 patients with treatment-resistant depression reported response rates of 90% and remission rates of 70% over 24 weeks.^[74] Schizophrenia involves reduced connectivity between the ACC and prefrontal cortex, as measured by diffusion tensor imaging (DTI) showing reduced fractional anisotropy in affected white matter tracts, indicating disrupted structural integrity and impaired executive function.^[75] Auditory hallucinations in schizophrenia are associated with abnormal gamma-band oscillations (40-80 Hz) involving the ACC and auditory cortices, where diminished phase synchronization correlates with hallucination severity.^[76] In anxiety disorders, decoupling between the amygdala and ACC contributes to heightened worry, with reduced functional connectivity predicting perseverative cognition and autonomic dysregulation over time.^[77] Recent studies highlight rACC involvement in feedback learning deficits, where enhanced theta oscillations during prediction error processing bias anxious individuals toward negative outcomes.^[78]

Neurodevelopmental and Toxicological Conditions

In autism spectrum disorder (ASD), structural abnormalities in the anterior cingulate cortex (ACC) include reduced gray matter volume, which contributes to impairments in social processing and cognitive control.^[79] Compared to neurotypical individuals, those with ASD exhibit smaller ACC volumes, alongside decreased glucose metabolism in this region, potentially disrupting error monitoring and response inhibition essential for social interactions. Additionally, some studies suggest alterations in von Economo neurons (also known as spindle cells), specialized projection neurons located in layer V of the ACC and frontoinsular cortex, potentially contributing to social deficits, though findings are inconsistent.^[80] Such structural and cellular alterations in the ACC are associated with core ASD symptoms like reduced social awareness and repetitive behaviors.^[81] Post-traumatic stress disorder (PTSD), particularly when arising from early-life trauma, involves ACC hyperresponsivity to threat-related stimuli, as evidenced by functional magnetic resonance imaging (fMRI) studies showing exaggerated activation in the dorsal ACC during cognitive control of emotional responses.^[82] This hyperactivation, observed in both affected individuals and those at familial risk, may heighten vigilance to potential dangers and contribute to persistent fear responses. Furthermore, during trauma recall tasks, PTSD is characterized by hyperactivity in the ACC-amygdala circuit, with increased BOLD signals in the amygdala and dorsal ACC to trauma-associated cues, leading to enhanced emotional reactivity and memory distortions for aversive events.^[83] This circuitry imbalance underscores the ACC's role in failed fear extinction following early adverse experiences. Chronic low-level lead exposure, defined as blood lead concentrations of 5-10 μg/dL, induces neurotoxic effects on the ACC, including cortical thinning and reduced gray matter volume in frontal regions encompassing the ACC, as documented in longitudinal studies of adults with childhood exposure.^[84] These changes correlate with cognitive deficits such as impairments in executive function, attention, and learning, persisting into adulthood despite cessation of exposure; pre-2020 cohort studies confirm that even subclinical levels below 10 μg/dL are sufficient to cause these outcomes, with no significant mechanistic updates in recent literature. Early hypo-connectivity in the ACC, particularly with default mode and salience networks, serves as a biomarker for increased risk of psychopathology across multiple disorders, including anxiety, depression, and schizophrenia. In children and adolescents, reduced ACC functional connectivity predicts transdiagnostic vulnerability, with studies indicating increased risk of developing mental health issues compared to those with typical connectivity. This hypo-connectivity, often linked to early adversity, reflects impaired integration of cognitive and emotional processing, heightening susceptibility to environmental stressors in neurodevelopment.^[85]

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Pain Affect Encoded in Human Anterior Cingulate But Not ... - Science
Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived ...
[31]
The anterior cingulate cortex and pain processing - Frontiers
Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize ...
[32]
A new perspective on the anterior cingulate cortex and affective pain
Apr 24, 2018 · Anterior cingulate cortex (ACC), which is activated by noxious and contextual stimuli, is involved in pain processing, especially affective pain.
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Role of the Anterior Cingulate Cortex in Translational Pain Research
Once the ACC activated by receiving nociceptive signals, it sends descending signals to other regions such as the nucleus accumbens and RVM [102, 103], and ...
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Long-term potentiation in the anterior cingulate cortex and chronic ...
Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex.
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Synaptic sensitization in the anterior cingulate cortex sustains the ...
Sep 10, 2024 · The latter induces a long-term potentiation (LTP) in the pyramidal dendrites that is necessary to experience both neuropathic and visceral pain.
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Synaptic potentiation of anterior cingulate cortex contributes to ...
Nov 6, 2021 · Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain ...
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A synaptic model for pain: long-term potentiation in the anterior ...
Jun 30, 2007 · I propose that ACC LTP may serve as a cellular model for studying central sensitization that related to chronic pain, as well as pain-related cognitive ...
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Neural circuits regulating visceral pain | Communications Biology
Apr 13, 2024 · In this review, we focus on the anterior cingulate cortex and paraventricular nucleus of the hypothalamus to highlight the progress in identifying the neural ...
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A meta-analysis of the anterior cingulate contribution to social pain
The first fMRI study assessing the neural correlates of social pain with the cyberball task (Eisenberger et al., 2003), which strongly impacted the scientific ...
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Role of anterior cingulate cortex inputs to periaqueductal gray for ...
Jul 11, 2022 · Our results indicate that increased signals from the ACC to the dl/lPAG might be critical for excessive fear avoidance in chronic pain disability.
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The contribution of periaqueductal gray in the regulation ... - Frontiers
Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance. ... cortex are involved in nociceptive modulation: A novel pain modulation ...
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Intrinsic functional connectivity of the periaqueductal gray, a resting ...
The periaqueductal gray (PAG) is known to play a crucial role in pain modulation and has shown a strong interaction with anterior cingulate cortex in previous ...
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[PDF] Normal Development of Brain Circuits - ACNP
Sep 30, 2009 · By GA week 8, neuroblasts begin to differentiate into either specific ... PCC, posterior cingulate cortex; ACC, anterior cingulate cortex ...
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Longitudinal stability of the folding pattern of the anterior cingulate ...
However, available data suggest that cortical shape within the anterior cingulate region is most-likely stable during the first years after birth, as evidenced ...
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The Basics of Brain Development - PMC - PubMed Central
Human brain development is a protracted process that begins in the third gestational week (GW) with the differentiation of the neural progenitor cells and ...
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Maturational Changes in Anterior Cingulate and Frontoparietal ...
dACC showed significantly greater modulation during error versus correct trials, with adults showing greater differential activity than adolescents or children.
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Puberty and structural brain development in humans - PMC
In summary, the adolescent brain continues to develop with volumetric, shape, and microstructural changes seen in both grey and white matter. Below, we review ...
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NMDA receptors and synaptic plasticity in the anterior cingulate cortex
Oct 1, 2021 · In the anterior cingulate cortex (ACC), NMDAR-dependent LTP plays an important role in injury-triggered cortical excitation and plastic changes.
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Significance of the anterior cingulate cortex in neurogenesis ...
Dec 22, 2023 · This review sheds light on the promising significance of the ACC in orchestrating postnatal and adult neurogenesis in conditions related to memory, cognitive ...
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The Formation of Recent and Remote Memory Is Associated with ...
Jun 24, 2009 · We present evidence that neuronal structural changes, ie, dendritic spine growth, develop sequentially in the hippocampus and anterior cingulate cortex (aCC)
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Treadmill Exercise Reverses Depression Model-Induced Alteration ...
Dendritic spines of the pyramidal neurons in the anterior cingulate cortex ... Mature BDNF increases spine formation and its level is upregulated by ...
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Anterior cingulate cortex: An fMRI analysis of conflict specificity ... - NIH
In this event‐related functional magnetic resonance imaging (fMRI) study, we provide evidence that the role of the anterior cingulate cortex (ACC) in ...
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fMRI at High Spatial Resolution: Implications for BOLD-Models
A typical voxel size in human fMRI is 3 × 3 × 3 mm3, which spans multiple ... fMRI studies in humans use an isotropic resolution of 0.75–0.8 mm. For ...
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Anterior cingulate cortex activity can be independent of response ...
Previous neuroimaging studies have shown that the presence of conflicting response alternatives in Stroop-like tasks increases activity in dorsal anterior ...
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Structural brain characteristics in treatment-resistant depression
Sep 2, 2019 · Patients showed significant volume reductions in frontal regions, in particular in the anterior cingulate cortex (ACC) and the prefrontal cortex ...Grey Matter Studies · Whole-Brain Vbm Studies · White Matter: Dti Studies...Missing: percentage | Show results with:percentage
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Brain structure alterations in depression: Psychoradiological evidence
MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment.Missing: percentage | Show results with:percentage
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The cingulum bundle: Anatomy, function, and dysfunction
The cingulum bundle is a prominent white matter tract that interconnects frontal, parietal, and medial temporal sites, while also linking subcortical nuclei ...
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Hippocampal volume and cingulum bundle fractional anisotropy are ...
The objective of this study was to investigate the relationship of medial temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as ...Missing: typical connectivity
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The interaction effect of high social support and resilience ... - Frontiers
May 19, 2024 · Our study employed ultra-high field rs-fMRI to explore how social support moderates the relationship between psychological resilience and functional ...
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Conceptualizing psychological resilience through resting-state ...
Jul 19, 2023 · This systematic review summarized resting-state fMRI findings in different modalities from various operationally defined resilience in a mentally healthy ...Missing: 2024 | Show results with:2024
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The error-related negativity (ERN) and psychopathology
The ERN is a negative deflection in event-related potential, peaking about 50 ms after an error, reflecting early error-processing activity.Missing: seminal | Show results with:seminal
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Feedback-related negativity (FRN) and theta oscillations
Difference waveforms (incorrect minus correct) showing the FRN at FCz electrode. FRN is more sensitive to the incorrect than correct outcome when the final ...
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Is Your Error My Concern? An Event-Related Potential ... - Frontiers
Electroencephalogram studies have identified an error-related event-related potential (ERP) component known as the error-related negativity or ERN, ...
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Anterior cingulate error-related activity is modulated by predicted ...
Our results also support the idea of a link between anterior cingulate activity and midbrain dopaminergic activity that encodes 'reward prediction errors', and ...
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Beta activity in human anterior cingulate cortex mediates reward ...
Jul 15, 2024 · We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward ...Missing: desynchronization | Show results with:desynchronization
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Neural dynamics of reward probability coding - Frontiers
Nov 17, 2013 · Here, we report a new MEG study investigating the spatio-temporal neural dynamics of prediction and reward prediction errors computations by ...
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Optogenetic Inhibition of Rat Anterior Cingulate Cortex Impairs the ...
May 15, 2024 · We found that ACC inactivation slowed and reduced the number of trials rats initiated and impaired both their accuracy and their ability to complete sessions.
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A study with fMRI and dynamic causal modeling - PubMed Central
We also hypothesized that dorsal ACC activity interferes with the Stroop task performance in OCD patients.Missing: percentage | Show results with:percentage
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[PDF] Error-Related Hyperactivity of the Anterior Cingulate Cortex in ...
Obsessive-compulsive disorder patients and healthy compar- ison subjects performed a simple cognitive task in which fMRI. BOLD signal localized neural responses ...Missing: hyperactivation | Show results with:hyperactivation
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Lesion location and outcome following cingulotomy for obsessive ...
Jul 9, 2021 · Long-term response rates following cingulotomy in patients with severe refractory OCD are reported at 35%–70%. The mechanism by which ...
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Anterior Cingulate Activity as a Predictor of Degree of Treatment ...
Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is ...
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Cingulate dynamics track depression recovery with deep brain ...
Sep 20, 2023 · Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD).
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Anterior cingulate cortex-related connectivity in first-episode ...
Concerning structural connectivity, major diffusion tensor imaging (DTI) findings highlighted a decreased fractional anisotropy (FA) value in the cingulate ...
[74]
Long-range synchrony of gamma oscillations and auditory ... - NIH
A significant positive correlation was found between auditory hallucination symptom scores and phase synchronization between the primary auditory cortices (p< ...
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Amygdala functional connectivity as a longitudinal biomarker ... - NIH
Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder.
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Anterior cingulate and medial prefrontal cortex oscillations underlie ...
Mar 15, 2023 · We show that oscillatory activity in the medial prefrontal, anterior cingulate and orbitofrontal cortex (mPFC, ACC, OFC) explains anxiety-related learning ...