Dominic S. Fareri

Reward-related processing in the human brain: Developmental considerations

The pursuit of rewarding experiences motivates everyday human behavior, and can prove beneficial when pleasurable, positive consequences result (e.g., satisfying hunger, earning a paycheck). However, reward seeking may also be maladaptive and lead to risky decisions with potentially negative long-term consequences (e.g., unprotected sex, drug use). Such risky decision making is often observed during adolescence, a time in which important structural and functional refinements occur in the brains reward circuitry. Although much of the brain develops before adolescence, critical centers for goal-directed behavior, such as frontal corticobasal ganglia networks, continue to mature. These ongoing changes may underlie the increases in risk-taking behavior often observed during adolescence. Further, typical development of these circuits is vital to our ability to make well-informed decisions; atypical development of the human reward circuitry can have severe implications, as is the case in certain clinical and developmental conditions (e.g., attention-deficit/hyperactivity disorder). This review focuses on current research probing the neural correlates of reward-related processing across human development supporting the current research hypothesis that immature or atypical corticostriatal circuitry may underlie maladaptive behaviors observed in adolescence.

Maternal Buffering of Human Amygdala-Prefrontal Circuitry During Childhood but Not During Adolescence

Mature amygdala-prefrontal circuitry regulates affect in adulthood but shows protracted development. In altricial and semialtricial species, caregivers provide potent affect regulation when mature neurocircuitry is absent. The present investigation examined a potential mechanism through which caregivers provide regulatory influences in childhood. Children, but not adolescents, showed evidence of maternal buffering, such that maternal stimuli suppressed amygdala reactivity. In the absence of maternal stimuli, children exhibited immature amygdala-prefrontal connectivity. However, in the presence of maternal stimuli, children’s connectivity was more mature, resembling adolescents’ connectivity. Children showed improved affect-related regulation in the presence of their mothers. Individual differences emerged, with greater maternal influence on amygdala-prefrontal circuitry associated with stronger mother-child relationships and maternal modulation of behavioral regulation. These findings suggest a neural mechanism through which caregivers modulate children’s regulatory behavior by inducing more mature connectivity and buffering against heightened reactivity. Maternal buffering in childhood, but not adolescence, suggests that childhood may be a sensitive period for amygdala-prefrontal development.

Effects of Direct Social Experience on Trust Decisions and Neural Reward Circuitry

The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball-tossing game with three fictional partners manipulated to be perceived as good, bad, or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball-tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction error learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning mechanisms.

Computational Substrates of Social Value in Interpersonal Collaboration

Decisions to engage in collaborative interactions require enduring considerable risk, yet provide the foundation for building and maintaining relationships. Here, we investigate the mechanisms underlying this process and test a computational model of social value to predict collaborative decision making. Twenty-six participants played an iterated trust game and chose to invest more frequently with their friends compared with a confederate or computer despite equal reinforcement rates. This behavior was predicted by our model, which posits that people receive a social value reward signal from reciprocation of collaborative decisions conditional on the closeness of the relationship. This social value signal was associated with increased activity in the ventral striatum and medial prefrontal cortex, which significantly predicted the reward parameters from the social value model. Therefore, we demonstrate that the computation of social value drives collaborative behavior in repeated interactions and provide a mechanistic account of reward circuit function instantiating this process.

Effects of early life stress on amygdala and striatal development

Highlights • Evaluating stimuli in terms of threat/reward is critical to survival.• The amygdala and striatum support affective valuation throughout life.• Absence of stable caregiving early in life disrupts normative affective development.• Such early life stress may alter the development of amygdala-striatal interactions.• Altered amygdala-striatal function may mediate onset of internalizing illness.

Social Rewards and Social Networks in the Human Brain

The rapid development of social media and social networking sites in human society within the past decade has brought about an increased focus on the value of social relationships and being connected with others. Research suggests that we pursue socially valued or rewarding outcomes—approval, acceptance, reciprocity—as a means toward learning about others and fulfilling social needs of forming meaningful relationships. Focusing largely on recent advances in the human neuroimaging literature, we review findings highlighting the neural circuitry and processes that underlie pursuit of valued rewarding outcomes across non-social and social domains. We additionally discuss emerging human neuroimaging evidence supporting the idea that social rewards provide a gateway to establishing relationships and forming social networks. Characterizing the link between social network, brain, and behavior can potentially identify contributing factors to maladaptive influences on decision making within social situations.

Normative development of ventral striatal resting state connectivity in humans

Incentives play a crucial role in guiding behavior throughout our lives, but perhaps no more so than during the early years of life. The ventral striatum is a critical piece of an incentive-based learning circuit, sharing robust anatomical connections with subcortical (e.g., amygdala, hippocampus) and cortical structures (e.g., medial prefrontal cortex (mPFC), insula) that collectively support incentive valuation and learning. Resting-state functional connectivity (rsFC) is a powerful method that provides insight into the development of the functional architecture of these connections involved in incentive-based learning. We employed a seed-based correlation approach to investigate ventral striatal rsFC in a cross-sectional sample of typically developing individuals between the ages of 4.5 and 23-years old (n=66). Ventral striatal rsFC with the mPFC showed regionally specific linear age-related changes in connectivity that were associated with age-related increases in circulating testosterone levels. Further, ventral striatal connectivity with the posterior hippocampus and posterior insula demonstrated quadratic age-related changes characterized by negative connectivity in adolescence. Finally, across this age range, the ventral striatum demonstrated positive coupling with the amygdala beginning during childhood and remaining consistently positive across age. In sum, our findings suggest that normative ventral striatal rsFC development is dynamic and characterized by early establishment of connectivity with medial prefrontal and limbic structures supporting incentive-based learning, as well as substantial functional reorganization with later developing regions during transitions into and out of adolescence.

Differential reward responses during competition against in- and out-of-network others

Social interactions occur within a variety of different contexts--cooperative/competitive--and often involve members of our social network. Here, we investigated whether social network modulated the value placed on positive outcomes during a competitive context. Eighteen human participants played a simple card-guessing game with three different competitors: a close friend (in-network), a confederate (out-of-network) and a random number generator (non-social condition) while undergoing functional magnetic resonance imaging. Neuroimaging results at the time of outcome receipt demonstrated a significant main effect of competitor across multiple regions of medial prefrontal cortex, with Blood Oxygen Level Dependent (BOLD) responses strongest when competing against ones friend compared with all other conditions. Striatal BOLD responses demonstrated a more general sensitivity to positive compared with negative monetary outcomes, which an exploratory analysis revealed to be stronger when interacting with social, compared with non-social, competitors. Interestingly, a Granger causality analysis indicated directed influences sent from an medial prefrontal cortex (mPFC) region, which shows social network differentiation of outcomes, and the ventral striatum bilaterally. Our results suggest that when competing against others of varying degrees of social network, mPFC differentially values these outcomes, perhaps treating in-network outcomes as more informative, leaving the striatum to more general value computations.

Previous Institutionalization Is Followed by Broader Amygdala-Hippocampal-PFC Network Connectivity during Aversive Learning in Human Development

Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala–hippocampal–prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7–16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7–16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS−). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS− trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal–subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience. SIGNIFICANCE STATEMENT Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function.

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this networks protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individuals stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development.