The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are ...supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer 18 Ffallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus and superior insula. These findings identify a link between a direct measure of mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.
Psychopathy is a personality disorder that is strongly linked to criminal behavior. Using 18Ffallypride positron emission tomography and blood oxygen level-dependent functional magnetic resonance ...imaging, we found that impulsive-antisocial psychopathic traits selectively predicted nucleus accumbens dopamine release and reward anticipation-related neural activity in response to pharmacological and monetary reinforcers, respectively. These findings suggest that neurochemical and neurophysiological hyper-reactivity of the dopaminergic reward system may comprise a neural substrate for impulsive-antisocial behavior and substance abuse in psychopathy.
Although research on aging and decision making continues to grow, the majority of studies examine decisions made to maximize monetary earnings or points. It is not clear whether these results ...generalize to other types of rewards. To investigate this, we examined adult age differences in 92 healthy participants aged 22 to 83. Participants completed 9 hypothetical discounting tasks, which included 3 types of discounting factors (time, probability, effort) across 3 reward domains (monetary, social, health). Participants made choices between a smaller magnitude reward with a shorter time delay/higher probability/lower level of physical effort required and a larger magnitude reward with a longer time delay/lower probability/higher level of physical effort required. Older compared with younger individuals were more likely to choose options that involved shorter time delays or higher probabilities of experiencing an interaction with a close social partner or receiving health benefits from a hypothetical drug. These findings suggest that older adults may be more motivated than young adults to obtain social and health rewards immediately and with certainty.
The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small ...samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese.
130 healthy subjects between 18 and 81years old underwent PET with 18Ffallypride, a high affinity DRD2/3 ligand.
As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum.
The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function.
•Age interacted with DRD2 availability in predicting BMI•Among subjects under 30years old, BMI was not associated with DRD2 availability.•Among subjects over 30years old, BMI positively associated with DRD2 availability.•Present results are incompatible with the dopaminergic hypofunction hypothesis.•Results highlight the importance of age in assessing correlates of DRD2 function.
Animal studies implicate the amygdala and its connections in the recognition of aversive stimuli. A recent PET study demonstrated that the human amygdala and left orbitofrontal cortex show ...substantial increases in regional cerebral blood flow (rCBF) during exposure to aversive odourants. To examine if aversive gustatory stimuli similarly activate these regions, nine healthy women tasted an aversive saline solution, pure water and chocolate while rCBF was measured with PET. The aversive saline condition, when contrasted with the water condition, increased activity in the right amygdala, left anterior orbitofrontal cortex, medial thalamus, pregenual and dorsal anterior cingulate, and the right hippocampus. The right amygdala, left orbitofrontal cortex and pregenual cingulate remained significantly activated when saline was compared with chocolate. The present results indicate that the amygdala and orbitofrontal cortex respond to aversive stimuli in both the olfactory and gustatory modalities, and highlight the role of the pregenual cingulate in negative emotional processing.
Mental disorders predict future occurrences of both the same disorder (homotypic continuity) and other disorders (heterotypic continuity). Heterotypic continuity is inconsistent with a view of mental ...disorders as fixed entities. In contrast, hierarchical-dimensional conceptualizations of psychopathology, in which each form of psychopathology is hypothesized to have both unique and broadly shared etiologies and mechanisms, predict both homotypic and heterotypic continuity.
To test predictions derived from a hierarchical-dimensional model of psychopathology that (1) heterotypic continuity is widespread, even controlling for homotypic continuity, and that (2) the relative magnitudes of heterotypic continuities recapitulate the relative magnitudes of cross-sectional correlations among diagnoses at baseline.
Ten prevalent diagnoses were assessed in the same person twice (ie, in 2 waves separated by 3 years). We used a representative sample of adults in the United States (i.e., 28,958 participants 18-64 years of age in the National Epidemiologic Study of Alcohol and Related Conditions who were assessed in both waves).
Diagnoses from reliable and valid structured interviews.
Adjusting for sex and age, we found that bivariate associations of all pairs of diagnoses from wave 1 to wave 2 exceeded chance levels (P < .05) for all homotypic (median tetrachoric correlation of ρ = 0.54 range, 0.41-0.79) and for nearly all heterotypic continuities (median tetrachoric correlation of ρ = 0.28 range, 0.07-0.50). Significant heterotypic continuity was widespread even when all wave 1 diagnoses (including the same diagnosis) were simultaneous predictors of each wave 2 diagnosis. The rank correlation between age- and sex-adjusted tetrachoric correlation for cross-sectional associations among wave 1 diagnoses and for heterotypic associations from wave 1 to wave 2 diagnoses was ρ = 0.86 (P < .001).
For these prevalent mental disorders, heterotypic continuity was nearly universal and not an artifact of failure to control for homotypic continuity. Furthermore, the relative magnitudes of heterotypic continuity closely mirrored the relative magnitudes of cross-sectional associations among these disorders, consistent with the hypothesis that both sets of associations reflect the same factors. Mental disorders are not fixed and independent entities. Rather, each diagnosis is robustly related to other diagnoses in a correlational structure that is manifested both concurrently and in patterns of heterotypic continuity across time.
•Greater activation in rostral anterior cingulate cortex (rACC) for high conflict.•Greater activation in medial superior frontal gyrus (MSFG) for high conflict.•rACC and MSFG had greater activation ...for conflict from nonemotional distracters.•Controls show more activation in right posterior MFG for high conflict emotional distracters.•OCD patients show more activation in right posterior MFG for low conflict emotional distracters.
Obsessive compulsive disorder (OCD) is associated with altered processing in brain regions involved in conflict resolution. However, limited research has examined the extent to which conflict from emotional distracters characterizes OCD such that responsiveness to task-irrelevant emotional stimuli is altered compared to controls. In the present study, 16 patients with OCD and 15 healthy controls underwent functional magnetic resonance imaging (fMRI) during resolution of conflict from emotional or nonemotional distracters. Results in healthy controls demonstrated that rostral anterior cingulate cortex (rACC), middle frontal gyrus (MFG), and medial superior frontal gyrus (MSFG) showed greater activation for high conflict versus low conflict. Responses in these regions differed between the emotional and nonemotional distracter tasks, with rACC and MSFG having greater activation for conflict from nonemotional distracters and anterior MFG showing greater activation for conflict from emotional distracters. Furthermore, between-group differences revealed a region in right posterior MFG in which controls similarly exhibited greater activation during high conflict versus low conflict with emotional distracters; however, OCD patients showed the opposite pattern with greater activation during low conflict compared to high conflict. These findings suggest that activity of right posterior MFG may be relevant in better understanding inefficient responding during emotional conflict in OCD.
Anhedonia is a core feature of major depressive disorder (MDD), but the precise nature of anhedonic symptoms is unknown. Whereas anhedonia has traditionally been viewed as a deficit in the experience ...of pleasure, more recent evidence suggests that reduced anticipation and motivation may also be a core feature of this symptom. Here, we provide data from a study in MDD patients and healthy controls using a translational measure of reward motivation, the Effort Expenditure for Rewards Task (EEfRT or "effort"). This task offers subjects a series of trials where they may choose to expend more or less effort for the opportunity to win varying amounts of monetary rewards. We found that MDD patients were less willing to expend effort for rewards than controls. Additionally, we observed that patients were less able to effectively use information about magnitude and probability of rewards to guide their choice behavior. Finally, within the MDD patient group, duration of the current episode was a significant negative predictor of EEfRT task performance. These findings offer novel support for theoretical models proposing that anhedonia in MDD may reflect specific impairments in motivation and reward-based decision-making.
Electrophysiologic and lesion studies of animals increasingly implicate the amygdala in aspects of emotional processing. Yet, the functions of the human amygdala remain poorly understood. To examine ...the contributions of the amygdala and other limbic and paralimbic regions to emotional processing, we exposed healthy subjects to aversive olfactory stimuli while measuring regional cerebral blood flow (rCBF) with positron emission tomography. Exposure to a highly aversive odorant produced strong rCBF increases in both amygdalae and in the left orbitofrontal cortex. Exposure to less aversive odorants produced rCBF increases in the orbitofrontal cortex but not in the amygdala. Change of rCBF within the left amygdala and the left OFC was highly intercorrelated, indicating a strong functional interaction between these brain regions. Furthermore, the activity within the left amygdala was associated significantly with subjective ratings of perceived aversiveness. These findings provide evidence that the human amygdala participates in the hedonic or emotional processing of olfactory stimuli.
Previous research indicates that the amygdala and hippocampus are sensitive to novelty; however, two types of novelty can be distinguished – stimuli that are ordinary, but novel in the current ...context, and stimuli that are unusual. Using functional magnetic resonance imaging, we examined blood oxygen dependent level (BOLD) response of the human amygdala and hippocampus to novel, commonly seen objects versus novel unusual objects. When presented with the novel common stimuli, the BOLD signal increased significantly in both the amygdala and hippocampus. However, for the novel unusual stimuli, only the amygdala showed an increased response compared to the novel common stimuli. These findings suggest that the amygdala is distinctly responsive to novel unusual stimuli, making a unique contribution to the novelty detection circuit.
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