Role Of Anterior Cingulate Cortex Research Articles

A special role for anterior cingulate cortex, but not orbitofrontal cortex or basolateral amygdala, in choices involving information.

Subjects are often willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No Info) vs. a leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%) and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the anterior cingulate cortex, orbitofrontal cortex, basolateral amygdala, or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of the anterior cingulate cortex destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that previous choice predicted current choice in all conditions, however previously rewarded Info trials strongly predicted preference in all conditions except in female rats following anterior cingulate cortex inhibition. The results reveal a causal, sex-dependent role for the anterior cingulate cortex in decisions involving information.

Photic sensitization is mediated by cortico-accumbens pathway in rats with trigeminal neuropathic pain

Exposure to light stimuli may trigger or exacerbate perception of pain, also known as a common yet debilitating symptom of photophobia in patient with chronic orofacial pain. Mechanism underlying this phenomenon of photic sensitization in neuropathic condition remains elusive. Here, we found that rats developed hypersensitivity to normal light illumination after establishment of chronic constriction injury of infraorbital nerve (ION-CCI) model, which can be attenuated by blocking the exposure of photic stimulation. Additionally, this behavioral phenotype of light-sensitivity impairment was associated with overexpression of anterior cingulate cortex (ACC) c-fos positive neurons, enhancement of neural excitability in the ACC neurons and its excitatory synaptic transmission between nucleus accumbens (NAc). Optogenetic and chemogenic silencing of ACC-NAc pathway improved trigeminal sensitization in responses to light stimuli by decreasing spontaneous pain-like episodes in ION-CCI animals. In contrast, selective activation of ACC-to-NAc circuits enhanced photic hypersensitivity in dark environment. Thus, our data provided novel role of ACC and its projection to NAc in bidirectional modulation of photic sensation, which may contribute to the understanding of photic allodynia in trigeminal neuropathic pain status.

Dysgranular retrosplenial cortex modulates histaminergic and nonhistaminergic itch processing

Itch is an unpleasant sensation followed by an intense desire to scratch. Previous researches have advanced our understanding about the role of anterior cingulate cortex and prelimbic cortex in itch modulation, whereas little is known about the effects of retrosplenial cortex (RSC) during this process. Here we firstly confirmed that the neuronal activity of dysgranular RSC (RSCd) is significantly elevated during itch-scratching processing through c-Fos immunohistochemistry and fiber photometry recording. Then with designer receptors exclusively activated by designer drugs approaches, we found that pharmacogenetic inhibition of global RSCd neurons attenuated the number of scratching bouts as well as the cumulative duration of scratching bouts elicited by both 5-HT or compound 48/80 injection into rats’ nape or cheek; selective inhibition of the pyramidal neurons in RSCd, or of the excitatory projections from caudal anterior cingulate cortex (cACC) to RSCd, demonstrated the similar effects of decreasing itch-related scratching induced by both 5-HT or compound 48/80. Pharmacogenetic intervention of the neuronal or circuitry activities did not affect rats’ motor ability. This study presents direct evidence that pyramidal neurons in RSCd, and the excitatory projection from cACC to RSCd are critically involved in central regulation of both histaminergic and nonhistaminergic itch.

Interleukin 6 associates with reduced grey matter volume and resting-state connectivity in the anterior cingulate cortex in bipolar patients

High levels of peripheral IL-6, a pro-inflammatory cytokine, have been indicated as a key element of the bipolar disorder (BD), allowing to differentiate BD from major depression with high accuracy and to early detect poor responders to antidepressant treatments. IL-6 may contribute to BD pathophysiology through its effects on the neurobiological underpinnings of the disorder, such as grey matter (GM) volumes and resting state functional connectivity (rs-FC) abnormalities. In this study, we primary investigate the relationship between the peripheral plasmatic level of IL-6 and GM volumes, obtained with Voxel-Based Morphometry, in 84 BD inpatients. As secondary aims, we explored if IL-6 levels may be related to self-reported psychopathological dimensions of depression (i.e. symptoms severity and cognitive biases) and seed based rs-FC of brain regions structurally associated with the cytokine. Results showed that higher level of peripheral IL-6 was associated to lower GM volumes in supragenual anterior cingulate cortex, and reduced rs-FC between this area and medial orbito-frontal cortex in BD. Furthermore, in depressed patients IL-6 positively correlated to cognitive biases typically associated to depressive episodes, such as the perceived uncontrollability of negative events, or their generalization across future and situations. Our data provide additional evidence of detrimental effect of systemic inflammation on brain structure in BD and confirm the crucial role of anterior cingulate cortex as neural underpinning of the disorder. However, future studies are needed to replicate our findings in larger samples.

Covariations between pupil diameter and supplementary eye field activity suggest a role in cognitive effort implementation.

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.

A role of anterior cingulate cortex in the emergence of worker–parasite relationship

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.

A central role for anterior cingulate cortex in the control of pathological aggression

Controlling aggression is a crucial skill in social species like rodents and humans and has been associated with anterior cingulate cortex (ACC). Here, we directly link the failed regulation of aggression in BALB/cJ mice to ACC hypofunction. We first show that ACC in BALB/cJ mice is structurally degraded: neuron density is decreased, with pervasive neuron death and reactive astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then triggers toxic astrogliosis. cFos expression across ACC indicated functional consequences: during aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed pathological aggression but left species-typical aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioral rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the central role of ACC in curbing pathological aggression.

Anterior Cingulate Cortex Lesions Abolish Budget Effects on Effort-Based Decision-Making in Rat Consumers.

Demand theory can be applied to analyze how animal consumers change their selection of commodities in response to changes in commodity prices, given budget constraints. Previous work has shown that demand elasticities in rats differed between uncompensated budget conditions in which the budget available to be spent on the commodities (e.g., the finite number of discrete operants to "purchase" rewards in two-alternative fixed-ratio schedules) was kept constant, and compensated budget conditions in which the budget was adjusted so that consumers could potentially continue to obtain the original reward bundles. Here, we hypothesized that rat anterior cingulate cortex (ACC) was necessary to produce this budget effect on demand elasticities. We applied excitotoxic or sham lesions to ACC in rats performing an effort task in which the prices of liquid vanilla or chocolate rewards (the effort required to obtain rewards) and the budget (the total number of operants) was manipulated. When reward prices changed, and the budget was compensated, all rats adjusted their demand for chocolate and vanilla accordingly. In sham-lesioned rats, changes in demand were even more pronounced when the budget was not compensated for the price changes. By contrast, ACC-lesioned animals did not show this additional budget effect. An in-depth comparison of the rats' choice patterns showed that, unlike sham rats, ACC-lesioned animals failed to maximize session-bundle utility after price/budget changes, revealing deficits in higher-order choice-strategy adaptations. Our results suggest a novel role of ACC in considering purchasing power during complex cost-benefit value computations.SIGNIFICANCE STATEMENT Anterior cingulate cortex (ACC) is important for allocating effort in cost-benefit calculations in animals and humans. Economic theory prescribes that the value of the costs in cost-benefit analyses not only depends on the net nominal costs required to purchase a reward, but also on the available budget resources, i.e., on the budget's "purchasing value." We asked whether ACC, a region implicated in effort-based decision-making and reward comparisons, is required for computing the value of effort relative to a budget constraint. Applying demand theory to describe rat choices in a rodent effort allocation task with varying effort prices and budgets, we show that ACC integrity was necessary for computing purchasing power, a core variable in economic choice theory.

Differential responses to breath-holding, voluntary deep breathing and hypercapnia in left and right dorsal anterior cingulate.

What is the central question of this study? What is the role of dorsal anterior cingulate cortex (ACC) in respiration control in humans? What is the main finding and its importance? Direct evidence is provided for a role of the ACC in respiratory control in humans. The neurophysiological responses in dorsal ACC to different breathing tasks varied and were different between left and right ACC. The role of subcortical structures and cerebral cortex in the maintenance of respiratory homeostasis in humans remains poorly understood. Emerging evidence suggests an important role of the anterior cingulate cortex (ACC) in respiratory control. In this study, local field potentials (LFPs) from dorsal ACC were recorded in humans through implanted deep brain electrodes during several breathing activities, including voluntary activities of breath-holding and deep breathing, and involuntary activities of inspiration of varying concentrations of carbon dioxide (1%, 3%, 5% and 7%). We found that the breath-holding task induced significant unilateral left-sided ACC changes in LFP power, including an increased activity in lower frequency bands (3-5Hz) and decreased activity in higher frequency bands (12-26Hz). The respiratory task involving reflex increase in ventilation due to hypercapnia (raised inspired CO2 ) was associated with bilateral changes in activity of the ACC (again with increased activity in lower frequency bands and reduced activity in higher frequency bands). The voluntary breathing task with associated hypocapnia (deep breathing) induced bilateral changes in activity within low frequency bands. Furthermore, probabilistic diffusion tractography analysis showed left-sided connection of the ACC with the insula and frontal operculum, and bilateral connections within subsections of the cingulate gyrus and the thalamus. This electrophysiological analysis provides direct evidence for a role of the ACC in respiratory control in humans.

The neural basis of predictive pursuit.

It remains unclear whether and, if so, how non-human animals make on-the-fly predictions during pursuit. Here, we used a novel laboratory pursuit task that incentivizes prediction of future prey positions. We trained three macaques to perform a joystick-controlled pursuit task in which prey follow intelligent escape algorithms. Subjects aimed towards the prey’s likely future positions, indicating that they generate internal predictions and use them to guide behavior. We then developed a generative model that explains real-time pursuit trajectories and showed that our subjects use prey position, velocity, and acceleration to make predictions. We identified neurons in the dorsal anterior cingulate cortex (dACC) whose responses track these three variables. These neurons multiplexed prediction-related variables with a distinct and explicit representation of the prey’s future position. Our results provide a clear demonstration that the brain can explicitly represent future predictions and highlight the critical role of anterior cingulate cortex for future-oriented cognition.

Direct neurophysiological evidence for a role of the human anterior cingulate cortex in central command.

The role of the anterior cingulate cortex (ACC) is still controversial. The ACC has been implicated in such diverse functions as cognition, arousal and emotion in addition to motor and autonomic control. Therefore the ACC is the ideal candidate to orchestrate cardiovascular performance in anticipation of perceived skeletal activity. The aim of this experiment was to investigate whether the ACC forms part of the neural network of central command whereby cardiovascular performance is governed by a top-down mechanism. Direct local field potential (LFP) recordings were made using intraparenchymal electrodes in six human ACC's to measure changes in neuronal activity during performance of a motor task in which anticipation of exercise was uncoupled from skeletal activity itself. Parallel cardiovascular arousal was indexed by electrocardiographic changes in heart rate. During anticipation of exercise, ACC LFP power within the 25-60 Hz frequency band increased significantly by 21% compared to rest (from 62.7 μV2/Hz (±SE 4.94) to 76.0μV2/Hz (±SE 7.24); p = 0.004). This 25-60 Hz activity increase correlated with a simultaneous heart rate increase during anticipation (Pearson's r = 0.417, p = 0.016). We provide the first invasive electrophysiological evidence to support the role of the ACC in both motor preparation and the top-down control of cardiovascular function in exercise. This further implicates the ACC in the body's response to the outside world and its possible involvement in such extreme responses as emotional syncope and hyperventilation. In addition we describe the frequency at which the neuronal ACC populations perform these tasks in the human.

Predicting Treatment Response in Depression: The Role of Anterior Cingulate Cortex.

BackgroundIdentification of biomarkers predicting therapeutic outcome of antidepressant treatment is one of the most important tasks in current research because it may transform the lengthy process of finding the right treatment for a given individual with depression. In the current study, we explored the potential of pretreatment pregenual anterior cingulate cortex activity as a putative biomarker of treatment response.MethodsThirty-two medication-free patients with depression were treated for 6 weeks with a selective serotonin reuptake inhibitor, escitalopram. Before treatment began, patients underwent an fMRI scan testing response to brief, masked, presentations of facial expression depicting sadness and happiness.ResultsAfter 6 weeks of treatment, there were 20 selective serotonin reuptake inhibitor responders and 12 nonresponders. Increased pretreatment pregenual anterior cingulate cortex activity to sad vs happy faces was observed in responders relative to nonresponders. A leave-one-out analysis suggested that activity in the anterior cingulate cortex was able to predict response status at the level of the individual participant.ConclusionsThe study supports the notion of pregenual anterior cingulate cortex as a promising predictor of antidepressant response.

Electrophysiological measures reveal the role of anterior cingulate cortex in learning from unreliable feedback.

Although a growing number of studies have investigated the neural mechanisms of reinforcement learning, it remains unclear how the brain responds to feedback that is unreliable. A recent theory proposes that the reward positivity (RewP) component of the event-related brain potential (ERP) and frontal midline theta (FMT) power reflect separate feedback-related processing functions of anterior cingulate cortex (ACC). In the present study, the electroencephalogram (EEG) was recorded from participants as they engaged in a time estimation task in which feedback reliability was manipulated across conditions. After each response, they received a cue that indicated that the following feedback stimulus was 100%, 75%, or 50% reliable. The results showed that participants' time estimates adjusted linearly according to the feedback reliability. Moreover, presentation of the cue indicating 100% reliability elicited a larger RewP-like ERP component than the other cues did, and feedback presentation elicited a RewP of approximately equal amplitude for all of the three reliability conditions. By contrast, FMT power elicited by negative feedback decreased linearly from the 100% condition to 75% and 50% condition, and only FMT power predicted behavioral adjustments on the following trials. In addition, an analysis of Beta power and cross-frequency coupling (CFC) of Beta power with FMT phase suggested that Beta-FMT communication modulated motor areas for the purpose of adjusting behavior. We interpreted these findings in terms of the hierarchical reinforcement learning account of ACC, in which the RewP and FMT are proposed to reflect reward processing and control functions of ACC, respectively.

Pure correlates of exploration and exploitation in the human brain.

Balancing exploration and exploitation is a fundamental problem in reinforcement learning. Previous neuroimaging studies of the exploration-exploitation dilemma could not completely disentangle these two processes, making it difficult to unambiguously identify their neural signatures. We overcome this problem using a task in which subjects can either observe (pure exploration) or bet (pure exploitation). Insula and dorsal anterior cingulate cortex showed significantly greater activity on observe trials compared to bet trials, suggesting that these regions play a role in driving exploration. A model-based analysis of task performance suggested that subjects chose to observe until a critical evidence threshold was reached. We observed a neural signature of this evidence accumulation process in the ventromedial prefrontal cortex. These findings support theories positing an important role for anterior cingulate cortex in exploration, while also providing a new perspective on the roles of insula and ventromedial prefrontal cortex.

Multi-modal imaging investigation of anterior cingulate cortex cytoarchitecture in neurodevelopment

Multi-modal imaging may improve our understanding of the relationship between cortical morphology and cytoarchitecture. To this end we integrated the analyses of several magnetic resonance imaging (MRI) and spectroscopy (MRS) metrics within the anterior cingulate cortex (ACC). Considering the ACCs role in neurodevelopmental disorders, we also investigated the association between neuropsychiatric symptoms and the various metrics. T1 and diffusion-weighted MRI and 1H-MRS (ACC voxel) data along with phenotypic information were acquired from children (8–12 years) with various neurodevelopmental disorders (n=95) and healthy controls (n=50). From within the MRS voxel mean diffusivity (MD) of the grey matter fraction, intrinsic curvature (IC) of the surface and concentrations of creatine, choline, glutamate, N-acetylaspartate and myo-inositol were extracted. Linear models were used to investigate if the neurochemicals predicted MD and IC or if MD predicted IC. Finally, measures of various symptom severities were included to determine the influence of symptoms of neurodevelopmental disorders. All five neurochemicals inversely predicted MD (all puncorrected<0.04, β=0.23–0.36). There was no association between IC and MD or IC and the neurochemicals (all p>0.05). Severity of autism symptoms related positively to MD (puncorrected=0.002, β=0.39). Our findings support the notion that the neurochemicals relate to cytoarchitecture within the cortex. Additionally, we showed that autism symptoms across participants relate to the ACC cytoarchitecture.

The Role of Anterior Cingulate Cortex in the Affective Evaluation of Conflict.

An influential theory of ACC function argues that this brain region plays a crucial role in the affective evaluation of performance monitoring and control demands. Specifically, control-demanding processes such as response conflict are thought to be registered as aversive signals by ACC, which in turn triggers processing adjustments to support avoidance learning. In support of conflict being treated as an aversive event, recent behavioral studies demonstrated that incongruent (i.e., conflict inducing), relative to congruent, stimuli can speed up subsequent negative, relative to positive, affective picture processing. Here, we used fMRI to investigate directly whether ACC activity in response to negative versus positive pictures is modulated by preceding control demands, consisting of conflict and task-switching conditions. The results show that negative, relative to positive, pictures elicited higher ACC activation after congruent, relative to incongruent, trials, suggesting that ACC's response to negative (positive) pictures was indeed affectively primed by incongruent (congruent) trials. Interestingly, this pattern of results was observed on task repetitions but disappeared on task alternations. This study supports the proposal that conflict induces negative affect and is the first to show that this affective signal is reflected in ACC activation.

S.28.02 - Top-down control in ADHD: disorder-specificity relative to CD, autism and OCD

Multi-modal imaging may improve our understanding of the relationship between cortical morphology and cytoarchitecture. To this end we integrated the analyses of several magnetic resonance imaging (MRI) and spectroscopy (MRS) metrics within the anterior cingulate cortex (ACC). Considering the ACCs role in neurodevelopmental disorders, we also investigated the association between neuropsychiatric symptoms and the various metrics. T1 and diffusion-weighted MRI and 1H-MRS (ACC voxel) data along with phenotypic information were acquired from children (8–12 years) with various neurodevelopmental disorders (n=95) and healthy controls (n=50). From within the MRS voxel mean diffusivity (MD) of the grey matter fraction, intrinsic curvature (IC) of the surface and concentrations of creatine, choline, glutamate, N-acetylaspartate and myo-inositol were extracted. Linear models were used to investigate if the neurochemicals predicted MD and IC or if MD predicted IC. Finally, measures of various symptom severities were included to determine the influence of symptoms of neurodevelopmental disorders. All five neurochemicals inversely predicted MD (all puncorrected<0.04, β=0.23–0.36). There was no association between IC and MD or IC and the neurochemicals (all p>0.05). Severity of autism symptoms related positively to MD (puncorrected=0.002, β=0.39). Our findings support the notion that the neurochemicals relate to cytoarchitecture within the cortex. Additionally, we showed that autism symptoms across participants relate to the ACC cytoarchitecture.

Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making.

When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for "continue" choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by "continue" choices was associated with growing activity and connectivity of a cortico-subcortical "braking" network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault "continue" choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making. Using a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision-making: First, we investigated an "inhibitory" network of regions that has so far been investigated with externally cued action inhibition. In this study, we show that the dynamics in this network under increasingly risky decisions are predictive of subjects' risk attitudes. Second, we contribute to a currently ongoing debate about the anterior cingulate cortex's role in sequential foraging decisions by showing that its activity is related to making nondefault choices rather than to choice uncertainty.

Distinct regions of anterior cingulate cortex signal prediction and outcome evaluation

A number of theories have been proposed to account for the role of anterior cingulate cortex (ACC) and the broader medial prefrontal cortex (mPFC) in cognition. The recent Prediction of Response Outcome (PRO) computational model casts the mPFC in part as performing two theoretically distinct functions: learning to predict the various possible outcomes of actions, and then evaluating those predictions against the actual outcomes. Simulations have shown that this new model can account for an unprecedented range of known mPFC effects, but the central theory of distinct prediction and evaluation mechanisms within ACC remains untested. Using combined computational neural modeling and fMRI, we show here that prediction and evaluation signals are indeed each represented in the ACC, and furthermore, they are represented in distinct regions within ACC.Our task independently manipulated both the number of predicted outcomes and the degree to which outcomes violated expectancies, the former providing assessment of regions sensitive to prediction and the latter providing assessment of regions sensitive to evaluation. Using quantitative regressors derived from the PRO computational model, we show that prediction-based model signals load on a network including the posterior and perigenual ACC, but outcome evaluation model signals load on the mid-dorsal ACC. These findings are consistent with distinct prediction and evaluation signals as posited by the PRO model and provide new perspective on a large set of known effects within ACC.

Effet antidépresseur de la kétamine : revue de la littérature sur les mécanismes d’action de la kétamine

In recent years, discovery of ketamine's fast and powerful antidepressant effects for treatment-resistant depression (TRD) has led to rethinking of the pathophysiology of depression. Numerous studies in humans and animals have focused on mechanisms of action underlying this effect, producing a number of explanatory pathways. The aim of this article is to summarize the various hypotheses underlying rapid antidepressant action of ketamine and therefore to better understand the mechanisms underlying depression and antidepressant action. Ketamine unique antidepressant properties have led to many studies on its neurobiological grounds. Intracellular signaling pathways such as mTOR, GSK3 or eEF2 seem to play a key role and are associated with an increased synaptic plasticity. Other hypotheses are discussed such as ketamine effects on neuro-inflammation, the role of anterior cingulate cortex in brain changes induced by ketamine, and the potential benefits of analgesic properties of ketamine in depressive disorders. Our review highlights the potential role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Understanding which pathways underlie the fast antidepressant effect of ketamine paves the way for the development of new antidepressants.