Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.     

Sex specificity of ventral anterior cingulate cortex suppression during a cognitive task

Ventral anterior cingulate cortex (vACC) is a highly interconnected brain region considered to reflect the sometimes competing demands of cognition and emotion. A reciprocal relationship between vACC and dorsal ACC (dACC) may play a role in maintaining this balance between cognitive and emotional processing. Using functional MRI in association with a cognitively-demanding visuospatial task (mental rotation), we found that only women demonstrated vACC suppression and inverse functional connectivity with dACC. Sex differences in vACC functioning--previously described under conditions of negative emotion--are extended here to cognition. Consideration of participant sex is essential to understanding the role of vACC in cognitive and emotional processing.     

Hypoactivation in the precuneus and posterior cingulate cortex during ambiguous decision making in individuals with HIV

Journal of NeuroVirology - People with human immunodeficiency virus (HIV) often have neurocognitive impairment. People with HIV make riskier decisions when the outcome probabilities are known, and...     

Neuronal encoding of subjective value in dorsal and ventral anterior cingulate cortex

We examined the activity of individual cells in the primate anterior cingulate cortex during an economic choice task. In the experiments, monkeys chose between different juices offered in variables amounts and subjective values were inferred from the animals' choices. We analyzed neuronal firing rates in relation to a large number of behaviorally relevant variables. We report three main results. First, there were robust differences between the dorsal bank (ACCd) and the ventral bank (ACCv) of the cingulate sulcus. Specifically, neurons in ACCd but not in ACCv were modulated by the movement direction. Furthermore, neurons in ACCd were most active before movement initiation, whereas neurons in ACCv were most active after juice delivery. Second, neurons in both areas encoded the identity and the subjective value of the juice chosen by the animal. In contrast, neither region encoded the value of individual offers. Third, the population of value-encoding neurons in both ACCd and ACCv underwent range adaptation. With respect to economic choice, it is interesting to compare these areas with the orbitofrontal cortex (OFC), previously examined. While neurons in OFC encoded both pre-decision and post-decision variables, neurons in ACCd and ACCv only encoded post-decision variables. Moreover, the encoding of the choice outcome (chosen value and chosen juice) in ACCd and ACCv trailed that found in OFC. These observations indicate that economic decisions (i.e., value comparisons) take place upstream of ACCd and ACCv. The coexistence of choice outcome and movement signals in ACCd suggests that this area constitutes a gateway through which the choice system informs motor systems.     

Posterior cingulate cortical lesions eliminate learning-related unit activity in the anterior cingulate cortex

The frequency of multi-unit neuronal firing in response to tonal conditional stimuli increases, and the neuronal responses become discriminative in character, in the anterior and posterior subfields of the cingulate cortex (Brodmann's Area 24 and 29, respectively) during the course of discriminative avoidance conditioning in rabbits. Bilateral electrolytic lesions of the dorsal subicular complex eliminated the training-induced excitatory response in both cortical subfields, suggesting that subiculocortical projection fibers are essential for this effect. Yet, available data indicate that the subicular projection reaches only Area 29, not Area 24. Here we test the hypothesis that the subicular influence attains Area 24 via a synaptic relay in Area 29. The results showed in keeping with the hypothesis, that bilateral aspirative or electrolytic lesions in Area 29 eliminated the training-induced neuronal responses in Area 24. As in the case of subicular lesions, the Area 29 lesions increased the amplitude of the macropotentials in Area 24. These results are discussed in relation to a model of the interactions of the cingulate cortex, hippocampus and the limbic thalamic nuclei during learning.     

Comparing the role of the anterior cingulate cortex and 6-hydroxydopamine nucleus accumbens lesions on operant effort-based decision making

Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost–benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post-operatively, excitotoxic ACC lesions caused a significant bias away from HR choices compared with sham-lesioned animals. There was no slowing in the speed of lever pressing and no correlation between time to complete the FR requirement and choice performance. Unexpectedly, no such alteration in choice allocation was observed in animals following 6-hydroxydopamine NAc lesions. However, these rats were consistently slower to initiate responding when cued to commence each trial and also showed a reduction in food hoarding on a species-typical foraging task. Taken together, this implies that only ACC lesions, and not 6-hydroxydopamine NAc lesions as performed here, cause a bias away from investing effort for greater reward when choosing between competing options.     

Neuronal activity during seizures in monkeys

From six monkeys with chronic alumina gel-induced epileptogenic foci a total of 44 neurons was recorded extracellularly before, during, and after spontaneous seizures. In all cases the unit activity was recorded when the monkeys were undrugged and awake. In six experiments two units were recorded simultaneously through the same electrode. Neurons near the periphery of the focus often ceased firing at the initiation of the ictal event, whereas units (both normal and epileptic) within the focus synchronized with both multiunit background activity and local field potential spikes just preceding the onset of clinical seizures. (The epileptic neurons appeared to synchronize before the normal cells.) During the clonic phase and/or generalization of the seizure, units both within and on the periphery of the focus fired in synchrony with local field potential spikes. These data indirectly support two concepts of focal epileptogenesis: (a) that an epileptogenic neuronal aggregate and (b) “pacemaker” epileptic neurons sustain the epileptogenicity of chronic foci.     

Neuronal activity in the monkey dorsolateral prefrontal cortex during a discrimination task with delay

Ninety-nine single neuron activities of the dorsolateral prefrontal cortex of 3 monkeys were recorded during performance of a Konorski task. Green or red lights were presented successively with a separation of fixed delay interval. The monkey responded as soon as the second stimulus was presented. If the two stimuli were color-matched, the ‘YES’ lever press was rewarded; if the two stimuli were not, the ‘NO’ lever press was rewarded. In the second task, after paired color stimuli, a tone pip was presented as the ‘GO’ signal for lever presses. During sample and matching periods 50 neurons increased their discharge rates and 10 decreased. In 86% of increasing type neurons rate increase occurred during both periods. During auditory GO periods, 27 neurons increased their rates and 11 decreased. Discharge peak was before or at the moment of hold key release. In 60% of these neurons were also observed the rate changes to sample and matching stimuli. Differential activations between left and right levers were found in 20%. It was suggested that the prefrontal cortex is related to a sensorial attention mechanism to the visual stimulus which enables correct choice of the behavior to be rewarded.     

Neuronal activity in the postcentral cortex related to force regulation during a precision grip task

Recordings from single neurons in the primary somatosensory cortex of the monkey during force regulation between the fingers showed following characteristics: the existence of classes of discharge patterns similar to those in motor cortex, but with differences in their distribution, a late onset of activity changes in relation to force increase and a linear relation to force, but with shallow mean rate-force slope.     

Modulation of subgenual anterior cingulate cortex activity with real-time neurofeedback

The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use real-time fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback.     

Oscillatory activity and phase-amplitude coupling in the human medial frontal cortex during decision making

Electroencephalogram oscillations recorded both within and over the medial frontal cortex have been linked to a range of cognitive functions, including positive and negative feedback processing. Medial frontal oscillatory characteristics during decision making remain largely unknown. Here, we examined oscillatory activity of the human medial frontal cortex recorded while subjects played a competitive decision-making game. Distinct patterns of power and cross-trial phase coherence in multiple frequency bands were observed during different decision-related processes (e.g., feedback anticipation vs. feedback processing). Decision and feedback processing were accompanied by a broadband increase in cross-trial phase coherence at around 220 msec, and dynamic fluctuations in power. Feedback anticipation was accompanied by a shift in the power spectrum from relatively lower (delta and theta) to higher (alpha and beta) power. Power and cross-trial phase coherence were greater following losses compared to wins in theta, alpha, and beta frequency bands, but were greater following wins compared to losses in the delta band. Finally, we found that oscillation power in alpha and beta frequency bands were synchronized with the phase of delta and theta oscillations ("phase-amplitude coupling"). This synchronization differed between losses and wins, suggesting that phase-amplitude coupling might reflect a mechanism of feedback valence coding in the medial frontal cortex. Our findings link medial frontal oscillations to decision making, with relations among activity in different frequency bands suggesting a phase-utilizing coding of feedback valence information.     

Selective anterior cingulate cortex deficit during conflict solution in schizophrenia: an event-related potential study

BACKGROUND: Schizophrenia research has gained a new focus on identification and further characterization of neurocognitive deficits in the search for behavioural endophenotypes of this disorder. The objective of this study was to explore differential cortical processing during executive control in schizophrenia as assessed with the attention network test (ANT). METHODS: Sixteen schizophrenic patients and sixteen healthy controls matched for gender, age, education, and nicotine consumption were tested with the ANT while recording 29-channel-electroencephalogram (EEG). Visual event-related potentials (ERP) N200 and P300 were topographically analyzed and cortical mapping using low resolution brain electromagnetic tomography (LORETA) was applied to localize neuroelectric generators of ERP. RESULTS: Behaviourally, significant differences between schizophrenic patients and controls were found only for the conflict condition (p<0.05) and for conflict adjusted by mean reaction time (p<0.01). Examining ERP of control subjects, N200 failed to show robust flanker congruency effects. P300 amplitude was reduced at Pz (p<0.05) and P300 latency was increased at Cz (p<0.005) for the conflict condition. Schizophrenic patients differed significantly in P300 latency at Cz during late conflict processing (p<0.005). Source analysis revealed a deficit in anterior cingulate cortex (p<0.05). CONCLUSION: Our results are in line with previous reports about dysfunctional ACC activation in schizophrenia and argue in favour of a selective deficit of cortical conflict resolution. It is further proposed that dysfunctional ACC activation during executive processing may be a neurophysiologic endophenotype candidate of schizophrenia.     

The role of the anterior cingulate cortex in pitch variation during sad affect

We examined neural activity, in the frontal lobes, associated with speech production during affective states. Using functional magnetic resonance imaging (fMRI), the blood oxygen level-dependent (BOLD) response to the overt reading of emotionally neutral sentences was measured before and after a happy or sad mood induction. There was no explicit demand to produce affect-congruent speech and a cover story was used to de-emphasize the significance of the speech task in light of our experimental aims. Each fMRI measurement was acquired 6 s after the onset of sentence presentation so that speech could be recorded while the scanner noise was minimal; speech parameters (e.g. pitch variation) were extracted from the sentences and regressed against fMRI data. In the sad group we found the predicted changes in affect and pitch variation. Further, the fMRI data confirmed our hypothesis in that the 'reading effect' (i.e. the BOLD response to reading minus the BOLD response to baseline stimuli) in the supracallosal anterior cingulate cortex covaried negatively with both pitch variation and affect. Our results suggest that the anterior cingulate cortex modulates paralinguistic features of speech during affective states, thus placing this neural structure at the interface between action and emotions.     

Learning and decision making in monkeys during a rock-paper-scissors game

Game theory provides a solution to the problem of finding a set of optimal decision-making strategies in a group. However, people seldom play such optimal strategies and adjust their strategies based on their experience. Accordingly, many theories postulate a set of variables related to the probabilities of choosing various strategies and describe how such variables are dynamically updated. In reinforcement learning, these value functions are updated based on the outcome of the player's choice, whereas belief learning allows the value functions of all available choices to be updated according to the choices of other players. We investigated the nature of learning process in monkeys playing a competitive game with ternary choices, using a rock-paper-scissors game. During the baseline condition in which the computer selected its targets randomly, each animal displayed biases towards some targets. When the computer exploited the pattern of animal's choice sequence but not its reward history, the animal's choice was still systematically biased by the previous choice of the computer. This bias was reduced when the computer exploited both the choice and reward histories of the animal. Compared to simple models of reinforcement learning or belief learning, these adaptive processes were better described by a model that incorporated the features of both models. These results suggest that stochastic decision-making strategies in primates during social interactions might be adjusted according to both actual and hypothetical payoffs.     

Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

In treatment trials for major depressive disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An analysis of covariance examining week-8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2 HamD percent change, and a significant three-way interaction of week-2 HamD percent change×treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining the mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response.     

Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task

An important function of the prefrontal cortex (PFC) is the control of goal-directed behaviour. This requires information as to whether actions were successful in obtaining desired outcomes such as rewards. While lesion studies implicate a particular PFC region, the orbitofrontal cortex (OFC), in reward processing, neurons encoding reward have been reported in both the OFC and the dorsolateral prefrontal cortex (DLPFC). To compare and contrast their roles, we recorded simultaneously from both areas while two rhesus monkeys (Macaca mulatta) performed a reward preference task. The monkeys had to choose between pictures associated with different amounts of a juice reward. Neuronal activity in both areas reflected the reward amount. However, neurons in the DLPFC encoded both the reward amount and the monkeys' forthcoming response, while neurons in the OFC more often encoded the reward amount alone. Further, reward selectivity arose more rapidly in the OFC than the DLPFC. These results are consistent with reward information entering the PFC via the OFC, where it is passed to the DLPFC and used to control behaviour.     

Changes in the electrical activity of the ventral hippocampus during stimulation of the anterior cingulate gyrus of the cat cortex

The results of anterior cingulate gyrus stimulation and cutting of the main cortical input to hippocampus (the entorhinal cortex) lead to the suggestion that the entorhinal cortex and the limbic thalamic nuclei are involved in the genesis of ventral hippocampus responses to anterior cingulate gyrus stimulation.     

Molecular mechanisms of pain in the anterior cingulate cortex

It is well known that peripheral sensory stimuli, including pain, trigger a series of neuronal activities along the somatosensory pathways as well as the neuronal network in the high brain structures. These neuronal activities not only produce appropriate physiological responses but also induce long-term plastic changes in some of the central synapses. It is believed that long-term synaptic changes help the brain to process and store new information. Such learning is critical for animals and humans to gain new knowledge of changing environment, generate appropriate emotional responses, and avoid dangerous stimuli in the future. In the case of permanent injury, however, the brain fails to distinguish the difference between "useful" and painful stimuli. Long-term synaptic changes work against the system and at least in part contribute to chronic pain. In this short article, the possible molecular mechanisms for long-term plasticity within the anterior cingulate cortex (ACC) will be discussed and reviewed, and it is hypothesized that potentiation of excitatory responses within the ACC contributes to chronic pain and pain-related mental disorders.     

Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia

OBJECTIVE: People with schizophrenia have exhibited reduced functional activity in the anterior cingulate cortex during the performance of many types of cognitive tasks and during the commission of errors. According to conflict theory, the anterior cingulate cortex is involved in the monitoring of response conflict, acting as a signal for a need for greater cognitive control. This study examined whether impaired conflict monitoring in people with schizophrenia could underlie reduced anterior cingulate activity during both correct task performance and error-related activity. METHOD: Functional activity in the anterior cingulate of 13 schizophrenia patients and 13 healthy comparison subjects was investigated by using event-related fMRI and a Stroop task that allowed simultaneous examination of activity during both conflict (incongruent trials) and error (commission of error trials). RESULTS: In the presence of comparable reaction time measures for conflict as well as comparable error rates, the schizophrenia subjects showed both decreased conflict- and error-related activity in the same region of the anterior cingulate cortex. Moreover, those with schizophrenia did not exhibit significant post-conflict or post-error behavioral adjustments. CONCLUSIONS: Concurrently reduced conflict- and error-related activity in the anterior cingulate cortex along with reduced trial-to-trial adjustments in performance has not previously been reported in schizophrenia. The current results suggest that impaired conflict monitoring by the anterior cingulate cortex might play an important role in contributing to cognitive control deficits in patients with schizophrenia.     

Neuronal activity in visual, auditory and polysensory areas in the monkey temporal cortex during visual fixation task

The activity of 252 neurons in the inferotemporal visual area TEO, the superior temporal auditory area (AA), and the superior temporal polysensory area (STP) during the performance of a visual spot-fixation task and two variations, blink and tone tests, was examined in two behaving monkeys. A considerable number of not only TEO cells (45%) but also AA (29%) and STP (34%) cells were activated during the spot-fixation task, but unresponsive to the blanking of the spot during the fixation stage in the blink test. In addition, it was found that the activity of a third of the TEO, AA and STP cells which fired during the task-start stage in the spot-fixation task was modulated by cross-interaction between spot and tone simultaneously presented in the tone test: among these, the spot-induced activity of all TEO cells was enhanced by the tone, whereas the spot-induced activity of all AA and STP cells was suppressed by the tone. These findings are discussed in relation to the process of attending selectively to a fixation-spot.