Correlates of economic decisions in the dorsal and subgenual anterior cingulate cortices.
ABSTRACT: The anterior cingulate cortex can be divided into distinct ventral (subgenual, sgACC) and dorsal (dACC), portions. The role of dACC in value-based decision-making is hotly debated, while the role of sgACC is poorly understood. We recorded neuronal activity in both regions in rhesus macaques performing a token-gambling task. We find that both encode many of the same variables; including integrated offered values of gambles, primary as well as secondary reward outcomes, number of current tokens and anticipated rewards. Both regions exhibit memory traces for offer values and putative value comparison signals. Both regions use a consistent scheme to encode the value of the attended option. This result suggests that neurones do not appear to be specialized for specific offers (that is, neurones use an attentional as opposed to labelled line coding scheme). We also observed some differences between the two regions: (i) coding strengths in dACC were consistently greater than those in sgACC, (ii) neurones in sgACC responded especially to losses and in anticipation of primary rewards, while those in dACC showed more balanced responding and (iii) responses to the first offer were slightly faster in sgACC. These results indicate that sgACC and dACC have some functional overlap in economic choice, and are consistent with the idea, inspired by neuroanatomy, which sgACC may serve as input to dACC.
Project description:Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown.Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD.Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture.We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called "warm glow" of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.
Project description:The dorsal anterior cingulate cortex (dACC) is thought to play a critical role in forming associations between rewards and actions. Currently available physiological data, however, remain inconclusive regarding the question of whether dACC neurons carry information linking particular actions to reward or, instead, encode abstract reward information independent of specific actions. Here we show that firing rates of a majority of dACC neurons in a population studied in an eight-option variably rewarded choice task were sensitive to both saccade direction and reward value. Furthermore, the influences of reward and saccade direction on neuronal activity were approximately equal in magnitude over the range of rewards tested and were statistically independent. Our results indicate that dACC neurons multiplex information about both reward and action, endorsing the idea that this area links motivational outcomes to behavior and undermining the notion that its neurons solely contribute to reward processing in the abstract.
Project description:BACKGROUND:The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting-state functional magnetic resonance imaging (RS-fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region. However, a recent meta-analysis on RS-fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity. METHODS:We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS-fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS-fMRI data from 88 heathy participants. RESULTS:(a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC-DLPFC and pgACC-DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC-sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC. CONCLUSIONS:Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC-DLPFC FC-based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions.
Project description:Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.
Project description:BACKGROUND:Major Depressive Disorder (MDD) is characterized by aberrant resting-state functional connectivity (FC) in anterior cingulate regions (e.g., subgenual anterior cingulate [sgACC]) and by negative emotional functioning that is inflexible or resistant to change. METHODS:MDD (N?=?33) and control (CTL; N?=?31) adults completed a resting-state scan, followed by a smartphone-based Experience Sampling Methodology (ESM) protocol surveying 10 positive and negative emotions 5 times per day for 21 days. We used multilevel modeling to assess moment-to-moment emotional inflexibility (i.e., strong temporal connections between emotions). We examined group differences in whole-brain FC analysis of bilateral sgACC, and then examined associations between emotional experiences and the extracted FC values within each group. RESULTS:As predicted, MDDs had inflexibility in sadness and avoidance (p < .001, FDR-corrected p < .05), indicating that these emotional experiences persist in depression. MDDs showed weaker FC between the right sgACC and pregenual/dorsal anterior cingulate (pg/dACC) than did CTLs (FWE-corrected, voxelwise p = .01). Importantly, sgACC-pg/dACC FC predicted sadness inflexibility in both MDDs (p?=?.046) and CTLs (p?=?.033), suggesting that sgACC FC is associated with day-to-day negative emotions. LIMITATIONS:Other maladaptive behaviors likely also affect the flexibility of negative emotions. We cannot generalize our finding of a positive relation between sgACC FC and inflexibility of sadness to individuals with more chronic depression or who have recovered from depression. CONCLUSIONS:Our preliminary findings suggest that connections between portions of the ACC contribute to the persistence of negative emotions and are important in identifying a brain mechanism that may underlie the maintenance of sadness in daily life.
Project description:Neurobiologists have studied decisions by offering successive, independent choices between goods or gambles. However, choices often have lasting consequences, as when investing in a house or choosing a partner. Here, humans decided whether to commit (by acceptance or rejection) to prospects that provided sustained financial return. BOLD signals in the rostral medial prefrontal cortex (rmPFC) encoded stimulus value only when acceptance or rejection was deferred into the future, suggesting a role in integrating value signals over time. By contrast, the dorsal anterior cingulate cortex (dACC) encoded stimulus value only when participants rejected (or deferred accepting) a prospect. dACC BOLD signals reflected two decision biases-to defer commitments to later, and to weight potential losses more heavily than gains-that (paradoxically) maximised reward in this task. These findings offer fresh insights into the pressures that shape economic decisions, and the computation of value in the medial prefrontal cortex.
Project description:Emotion perception deficits could be due to disrupted connectivity of key nodes in the salience and emotion network (SEN), including the amygdala, subgenual anterior cingulate cortex (sgACC), and insula. We examined SEN resting-state (rs-)fMRI connectivity in rMDD in relation to Facial Emotion Perception Test (FEPT) performance. Fifty-two medication-free people ages 18 to 23 years participated. Twenty-seven had major depressive disorder (MDD) in remission (rMDD, 10 males), as MDD is associated with emotion perception deficits and alterations in rsfMRI. Twenty-five healthy controls (10 males) also participated. Participants completed the FEPT during fMRI, in addition to an 8-minute eyes-open resting-state scan. Seed regions of interest were defined in the amygdala, anterior insula and sgACC. Multiple regression analyses co-varied diagnostic group, sex and movement parameters. Emotion perception accuracy was positively associated with connectivity between amygdala seeds and regions primarily in the SEN and cognitive control network (CCN), and also the default mode network (DMN). Accuracy was also positively associated with connectivity between the sgACC seeds and other SEN regions, and the DMN, particularly for the right sgACC. Connectivity negatively associated with emotion perception was mostly with regions outside of these three networks, other than the left insula and part of the DMN. This study is the first to our knowledge to demonstrate relationships between facial emotion processing and resting-state connectivity with SEN nodes and between SEN nodes and regions located within other neural networks.
Project description:Very few studies have been performed to understand the underlying neural substrates of adolescent major depressive disorder (MDD). Studies in depressed adults have demonstrated that the subgenual anterior cingulate cortex (sgACC) plays a pivotal role in depression and have revealed aberrant patterns of resting-state functional connectivity (RSFC). Here, we examine the RSFC of the sgACC in medication-naïve first-episode adolescents with MDD.Twenty-three adolescents with MDD and 36 well-matched control subjects underwent functional magnetic resonance imaging to assess the RSFC of the sgACC.We observed elevated connectivity between the sgACC and the insula and between the sgACC and the amygdala in the MDD group compared with the control subjects. Decreased connectivity between the sgACC and the precuneus was also found in the MDD group relative to the control subjects. Within the MDD group, higher levels of depression significantly correlated with decreased connectivity between the sgACC and left precuneus. Increased rumination was significantly associated with reduced connectivity between sgACC and the middle and inferior frontal gyri in the MDD group.Our study is the first to examine sgACC connectivity in medication-naïve first-episode adolescents with MDD compared with well-matched control participants. Our results suggest aberrant functional connectivity among the brain networks responsible for salience attribution, executive control, and the resting-state in the MDD group compared with the control participants. Our findings raise the possibility that therapeutic interventions that can restore the functional connectivity among these networks to that typical of healthy adolescents might be a fruitful avenue for future research.
Project description:BACKGROUND: Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC). METHODS: Resting brain glucose metabolism (GM) was measured using [(18)F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively. RESULTS: Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA ??=?-0.248, p?=?0.003; ST: ??=?0.250, p?=?0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x?=?-8, y?=?32, z?=?-8, k?=?423, Z?=?4.41, corrected p (FDR)?=?0.030). CONCLUSION: The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.
Project description:Rodent fear-learning models posit that amygdala-infralimbic connections facilitate extinction while amygdala-prelimbic prefrontal connections mediate fear expression. Analogous amygdala-prefrontal circuitry between rodents and primates is not established. Using paired small volumes of neural tracers injected into the perigenual anterior cingulate cortex (pgACC; areas 24b and 32; a potential homologue to rodent prelimbic cortex) and subgenual anterior cingulate cortex (sgACC, areas 25 and 14c; a potential homologue to rodent infralimbic cortex) in a single hemisphere, we mapped amygdala projections to the pgACC and sgACC within single subjects. All injections resulted in dense retrograde labeling specifically within the intermediate division of the basal nucleus (Bi) and the magnocellular division of the accessory basal nucleus (ABmc). Areal analysis revealed a bias for connectivity with the sgACC, with the ABmc showing a greater bias than the Bi. Double fluorescence analysis revealed that sgACC and pgACC projections were intermingled within the Bi and ABmc, where a proportion were double labeled. We conclude that amygdala inputs to the ACC largely originate from the Bi and ABmc, preferentially connect to the sgACC, and that a subset collaterally project to both sgACC and pgACC. These findings advance our understanding of fear extinction and fear expression circuitry across species.