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.     

Effects of choice on neuronal activity in anterior cingulate,prelimbic, and infralimbic cortices in the rat: Comparison of serial lever pressing with delayed nonmatching to position

The ability to choose between response alternatives based on their likely consequences depends on distributed neural circuits that involve rodent medial prefrontal cortex (mPFC). To understand the effects of choice on mPFC function, we compared the activity of mPFC neurons in rats performing two tasks: dynamic delayed nonmatching to position (dDNMTP), a task with a prefrontal‐dependent conditional choice, and serial lever pressing (SLP), a task lacking a choice but trained in the same apparatus with sequences of actions and reinforcements matched to dDNMTP. More neurons exhibited event‐related responses during dDNMTP than SLP. Average firing rate during recording sessions was higher during dDNMTP for neurons with event‐related responses, but lower for neurons with activity unrelated to behavioural events. Thus, compared to SLP, dDNMTP appears to enhance the activity of neurons that represent behaviourally relevant information and to suppress the activity of neurons that do not. dDNMTP was associated with responses related to preparation and memory delay that were not observed during SLP as well as enhanced responses related to movement and reinforcement. These results provide evidence that choice in the dDNMTP task is associated with adaptive changes in background firing rates and coding properties of mPFC neurons.     

Neurons in the pigeon nidopallium caudolaterale signal the selection and execution of perceptual decisions

Sensory systems provide organisms with information on the current status of the environment, thus enabling adaptive behavior. The neural mechanisms by which sensory information is exploited for action selection are typically studied with mammalian subjects performing perceptual decision‐making tasks, and most of what is known about these mechanisms at the single‐neuron level is derived from cortical recordings in behaving monkeys. To explore the generality of neural mechanisms underlying perceptual decision making across species, we recorded single‐neuron activity in the pigeon nidopallium caudolaterale (NCL), a non‐laminated associative forebrain structure thought to be functionally equivalent to mammalian prefrontal cortex, while subjects performed a visual categorisation task. We found that, whereas the majority of NCL neurons unspecifically upregulated or downregulated activity during stimulus presentation, ~20% of neurons exhibited differential activity for the sample stimuli and predicted upcoming choices. Moreover, neural activity in these neurons was ramping up during stimulus presentation and remained elevated until a choice was initiated, a response pattern similar to that found in monkey prefrontal and parietal cortices in saccadic choice tasks. In addition, many NCL neurons coded for movement direction during choice execution and differentiated between choice outcomes (reward and punishment). Taken together, our results implicate the NCL in the selection and execution of operant responses, an interpretation resonating well with the results of previous lesion studies. The resemblance of the response patterns of NCL neurons to those observed in mammalian cortex suggests that, despite differing neural architectures, mechanisms for perceptual decision making are similar across classes of vertebrates.     

Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder

Singh MK, Chang KD, Chen MC, Kelley RG, Garrett A, Mitsunaga MM, Bararpour L, Howe M, Reiss AL, Gotlib IH. Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder.
Bipolar Disord 2012: 14: 585–596. © 2012 The Authors.
Journal compilation © 2012 John Wiley & Sons A/S. Objectives: A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities. Methods: Anatomical images from magnetic resonance imaging of 26 13‐ to 18‐year‐old adolescents with bipolar I disorder and 24 age‐comparable healthy controls with no personal or family history of psychopathology were analyzed using whole‐brain voxel‐based morphometry (VBM). Results: Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p < 0.05, family‐wise error (FWE)‐corrected]. Conclusions: Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.     

Cross-modal sensory processing in the anterior cingulate and medial prefrontal cortices

One of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross-modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross-modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated.     

The anterior insular and anterior cingulate cortices in emotional processing for self-face recognition

Individuals can experience embarrassment when exposed to self-feedback images, depending on the extent of the divergence from the internal representation of the standard self. Our previous work implicated the anterior insular cortex (AI) and the anterior cingulate cortex (ACC) in the processing of embarrassment; however, their exact functional contributions have remained uncertain. Here, we explored the effects of being observed by others while viewing self-face images on the extent of embarrassment, and the activation and connectivity patterns in the AI and ACC. We conducted functional magnetic resonance imaging hyperscanning in pairs of healthy participants using an interaction system that allowed an individual to be observed by a partner in real time. Being observed increased the extent of embarrassment reported when viewing self-face images; a corresponding increase in self-related activity in the right AI suggested that this region played a direct role in the subjective experience. Being observed also increased the functional connectivity between the caudal ACC and prefrontal regions, which are involved in processing the reflective self. The ACC might therefore serve as a hub, integrating information about the reflective self that is used in evaluating perceptual self-face images.     

Characterization of serial order encoding in the monkey anterior cingulate sulcus

In a previous report we showed that neurons in the anterior cingulate cortex might encode the serial order of the three components (first, second and third) of motor sequences, irrespective of which component is performed, and irrespective of the component that precedes or follows. Here we further explore these data by comparing the magnitude of cell activity at the different ranks. We also compare the activity recorded in the motor sequences and in tasks with only one motor component. We finally discuss functional hypotheses, which may account for the serial order encoding.     

Opiate addicts lack error-dependent activation of rostral anterior cingulate.

BACKGROUND: Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets. Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and, given generally poorer performance on such tasks by addicts, whether this signal is disrupted in addiction. METHODS: We used rapid, event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task. RESULTS: Compared with controls, opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance. In controls, the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance, particularly sensitivity in discriminating targets from nontargets. CONCLUSIONS: The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior.     

Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition.

BACKGROUND: Choosing between actions associated with uncertain rewards and punishments is mediated by neural circuitry encompassing the orbitofrontal cortex, anterior cingulate cortex (ACC), and striatum; however, the precise conditions under which these different components are activated during decision-making cognition remain uncertain. METHODS: Fourteen healthy volunteers completed an event-based functional magnetic resonance imaging protocol to investigate blood-oxygenation-level-dependent (BOLD) responses during independently modeled phases of choice cognition. In the "decision phase," participants decided which of two simultaneous visually presented gambles they wished to play for monetary reward. The gambles differed in their magnitude of gains, magnitude of losses, and the probabilities with which these outcomes were delivered. In the "outcome phase," the result of each choice was indicated on the visual display. RESULTS: In the decision phase, choices involving large gains were associated with increased BOLD responses in the pregenual ACC, paracingulate, and right posterior orbitolateral cortex compared with choices involving small gains. In the outcome phase, good outcomes were associated with increased BOLD responses in the posterior orbitomedial cortex, subcallosal ACC, and ventral striatum compared with negative outcomes. There was only limited overlap between reward-related activity in ACC and orbitofrontal cortex during the decision and outcome phases. CONCLUSIONS: Neural activity within the medial and lateral orbitofrontal cortex, pregenual ACC, and striatum mediate distinct representations of reward-related information that are deployed at different stages during a decision-making episode.     

The origin of projections from the posterior cingulate and retrosplenial cortices to the anterior,medial dorsal and laterodorsal thalamic nuclei of macaque monkeys

Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition.     

The anterior cingulate cortex: Monitoring the outcomes of others' decisions

The implicit positive association (IPA) theory attributed self-face advantage to the IPA with self-concept. Previous behavioral study has found that self-concept threat (SCT) could eliminate the self-advantage in face recognition over familiar-face, without taking levels of facial familiarity into account. The current event-related potential study aimed to investigate whether SCT could eliminate the self-face advantage over stranger-face. Fifteen participants completed a “self-friend” comparison task in which participants identified the face orientation of self-face and friend-face after SCT and non-self-concept threat (NSCT) priming, and a “self-stranger” comparison task was also completed in which participants identified the face orientation of self-face and stranger-face after SCT and NSCT priming. The results showed that the N2 amplitudes were more negative for processing friend-face than self-face after NSCT priming, but there was no significant difference between them after SCT priming. Moreover, the N2 amplitudes were more negative for processing stranger-face than self-face both after SCT priming and after NSCT priming. Furthermore, SCT manipulated the N2 amplitudes of friend-face rather than self-face. Overall, the present study made a supplementary to the current IPA theory and further indicated that SCT would only eliminate this self-face recognition advantage when comparing with important others.     

The effects of ethanol on diverse components of choice in the rat: reward discrimination,preference and relative valuation

Alcohol consumption impairs judgment and choice. How alcohol alters these crucial processes is primarily unknown. Choice can be fractionated into different components including reward discrimination, preference and relative valuation that can function together or in isolation depending upon diverse factors including choice context. We examined the diverse components and contextual effects by analyzing the effects of alcohol drinking on choice behavior in a task with a reduced level of temporal and spatial constraints. Rats were trained to drink 10% ethanol during 6 weeks of behavior testing using a combined sucrose‐fade and two‐bottle free‐choice procedure. Two different sucrose pellet outcomes (e.g., constant vs. variable) were presented each week to examine the impact of voluntary drinking on reward‐based decision‐making. Behavioral contexts of single option, free choice and extinction were examined for each outcome set. Comparisons were made between alcohol and control groups and within the alcohol group over time to inspect choice profiles. Between‐group results showed alcohol drinking animals expressed altered place preference and modified sucrose reward approach latencies. The within‐group profile showed that alcohol drinking animals can express adequate reward discrimination, preference and incentive contrast during free choice. All of these components were significantly reduced during the context of extinction. Control animals were also impacted by extinction but not as severely. The findings point to a need for a greater focus on the context and the diverse components of choice when examining external and internal factors influencing decision‐making during alcohol or other substance of abuse exposure.     

Hippocampal interplay with the nucleus accumbens is critical for decisions about time

Human cognition depends upon the capacity to make decisions in the present that bear upon outcomes in the future. The nucleus accumbens, a recipient of direct projections from both the hippocampus and orbitofrontal cortex, is known to contribute to these aspects of decision‐making. Here we demonstrate that interaction of the nucleus accumbens with the hippocampus, but not the orbitofrontal cortex, is critical in shaping decisions that involve time trade‐offs. Compared with controls, rats with a disrupted hippocampal–accumbens interaction were strongly biased toward choosing stimuli that led to small and immediate food rewards over large and delayed ones. We show that this pattern of behavior cannot be ascribed to the impaired representation of stimulus value, the incapacity to wait, or a general disruption of decision‐making. These results identify a hippocampal–accumbens circuit that may underlie a range of problems in which daily decisions are marked by a shift toward immediate gratification.     

Role of the right temporoparietal junction in intergroup bias in trust decisions

Intergroup bias, which is the tendency to behave more positively toward an in‐group member than toward an out‐group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in‐group or out‐group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in‐group members were significantly higher than those with out‐group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.     

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.     

Evidence that the anterior cingulate and supplementary somatosensory cortices generate the pain-related negative difference potential.

OBJECTIVE: The pain-related negative difference potential (NDP) is derived by subtracting sural nerve-evoked somatosensory evoked potentials elicited at the pain threshold level from those elicited at supra-pain threshold levels. This experiment evaluated a hypothesis derived from our earlier work, namely that the NDP is generated by pain-related activity in the primary somatosensory (SI) cortex. METHODS: The dipole source localization method was applied to NDPs evoked by electrical stimulation of the finger and of the sural nerve in 20 subjects. RESULTS: Comparison of several one-, two- and three-source configurations demonstrated that both the finger-evoked NDP and the sural nerve-evoked NDP are best-fit by two sources, with one located in or near the anterior cingulate cortex and the other in or near the supplementary somatosensory area. CONCLUSIONS: Both the anterior cingulate cortex and the supplementary somatosensory area receive afferent projections from medial thalamic nuclei that receive nociceptive inputs, and both have been shown to respond to noxious stimulation. Hence, although the results of this experiment did not confirm our hypothesis that the NDP is generated in SI, they are consistent with the hypothesis that the NDP is generated in the supraspinal pain pathways.     

The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal–amygdala neural circuitry during positive‐social emotion regulation

Positive‐social emotions mediate one's cognitive performance, mood, well‐being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top‐down signals that stem from the prefrontal cortices (PFC) which modulate bottom‐up emotional responses in the amygdala. However, it remains unclear if positive‐social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive‐social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive‐social emotion upregulation was associated with an increase in top‐down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.     

Alterations in reward-related decision making in boys with recent and future depression.

BACKGROUND: Altered reward processing is postulated to be a feature of depression. Reward processing may be valuable to understanding early-onset depressive disorders, which tend to be chronic and recurrent. METHODS: Reward-related decision making was examined within a longitudinal study of 221 11-year-old boys, 25 of whom had a depressive disorder at age 10 or 11. Participants completed a behavioral decision-making task involving varying probability and magnitude of obtaining reward. RESULTS: Under conditions involving a high probability of winning, boys with depression failed to distinguish between options involving small or large possible reward. Boys with anxiety or externalizing disorders at age 10 or 11 did not differ from others in their reward-related decisions. Low frequency of choosing the high-probability, large reward option at age 11 predicted depressive disorders, anxiety disorders, and depressive symptoms 1 year later. Furthermore, reward-related decisions predicted later depressive or anxiety disorders even when adjusting for the continuity of such disorders and the presence of concurrent externalizing disorders. CONCLUSIONS: Findings are consistent with affective neuroscience models of altered reward processing and diminished positive affect in depression. This study represents a step toward elucidating the motivational and emotional aspects of early-onset depression.     

Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients

Background

Obsessive Compulsive Disorder (OCD) is a chronic and disabling disorder with poor response to pharmacological treatments. Converging evidences suggest that OCD patients suffer from dysfunction of the cortico-striato-thalamo-cortical (CSTC) circuit, including in the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC).