25 : Adversity Fix
Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.
25 : Adversity
Children who have experienced environmental adversity-such as abuse, neglect, or poverty-are more likely to develop physical and mental health problems, perform poorly at school, and have difficulties in social relationships than children who have not encountered adversity. What is less clear is how and why adverse early experiences exert such a profound influence on children's development. Identifying developmental processes that are disrupted by adverse early environments is the key to developing better intervention strategies for children who have experienced adversity. Yet, much existing research relies on a cumulative risk approach that is unlikely to reveal these mechanisms. This approach tallies the number of distinct adversities experienced to create a risk score. This risk score fails to distinguish between distinct types of environmental experience, implicitly assuming that very different experiences influence development through the same underlying mechanisms. We advance an alternative model. This novel approach conceptualizes adversity along distinct dimensions, emphasizes the central role of learning mechanisms, and distinguishes between different forms of adversity that might influence learning in distinct ways. A key advantage of this approach is that learning mechanisms provide clear targets for interventions aimed at preventing negative developmental outcomes in children who have experienced adversity.
A dimensional model of childhood adversity involving two central dimensions of threat and deprivation. Examples of commonly studied forms of adversity are placed along these dimensions based on the degree to which the experience typically involves threat and deprivation. Larger circles indicate greater variance in the degree to which the experience reflects the underlying dimension.
Increasing evidence has implicated the neural circuitry of reward in altered brain function resulting from exposure to early life adversity. At the behavioral level, impaired responding to rewarding stimuli in maltreated individuals was reported . These individuals exhibited faster reactions for risky options in a decision-making task than controls, but lacked the typical increase in response speed with the chance of winning. Further evidence for a reduced sensitivity to reward was provided in an fMRI study . Young adults maltreated during childhood showed a blunted basal ganglia response (left putamen, left globus pallidus) and less positive ratings of reward cues during reward anticipation. Another study underscored these results by demonstrating a decreased activation in the VS to reward-predicting cues in Romanian adoptees who had experienced global early deprivation . In these studies, no effect of early adversity on reward delivery was observed, suggesting that adversity might specifically affect responses to reward-predicting cues. However, a recent study by Kumar et al.  investigating the impact of acute stress found differential effects on phases of reward processing, with increased neuronal activation in the caudate and the amygdala during reward anticipation and decreased activation in the caudate and the putamen while receiving a reward. Hence, acute and early chronic stress seem to impact on the anticipatory and delivery stage of reward processing in specific ways, most likely mediated by alterations of the hypothalamus-pituitary-adrenal (HPA) axis .
In the present study, the impact of early adversity on reward processing was examined in a large sample of young adults from an epidemiological cohort study followed since birth. Using a monetary incentive delay (MID) task offering either money or verbal feedback, simultaneous EEG-fMRI was recorded in order to detect alterations at different stages of reward processing. Given the fact that the verbal feedback (control condition) of the MID represents a special reward characteristic, such as if receiving a social reward , , modality-specific differences in rewarding quality will be examined. The use of EEG and fMRI provides both high spatial and temporal resolution of neuronal alterations during reward processing. Especially, the EEG enables a cue related analysis of time-resolved neurophysiological signatures within the anticipation phase as recently demonstrated by Plichta et al. . First, we hypothesized that activation of reward-related areas induced by the anticipation of a monetary reward, especially the VS, would decrease with the level of early adversity. Second, we expected the same effect for the EEG, i.e. that the CNV, reflecting the motivational signature of reward anticipation, would decrease with increasing adversity. Third, in line with previous research, no adversity-specific alterations of the neuronal response to monetary reward outcome were predicted , . Fourth, we hypothesized that reward-related neuronal activation was related to lifetime ADHD symptoms, showing decreasing neuronal activity during reward anticipation and increasing activation during reward delivery with the level of ADHD , , .
The current simultaneous EEG-fMRI study investigated the long-term impact of early life adversity on neuronal alterations of the reward system into adulthood. Using data of an epidemiological cohort study from birth onwards, the results presented above provided evidence of altered reward processing later in life following exposure to early adversity. Specifically, our findings demonstrated a differential impact of adversity on neural responding to distinct phases of reward processing, indicating that the activation of specific reward-related brain areas (VS, putamen, thalamus) decreased with the level of adversity during reward anticipation, while there was an increase in activity of other reward-related areas (pallidum, insula, substantia nigra, right posterior hippocampus) with the level of adversity during reward delivery. The fMRI finding during reward anticipation converged with EEG results showing a negative association between the CNV and adversity, matching the negative correlation of CNV with fMRI activation. Further analysis of the single reward conditions revealed striking effects of early adversity on the processing of verbal reward, which accounted for major parts of the total reward-related activity during the delivery phase.
The results of the present study replicate recent findings with regard to reward anticipation , , highlighting deficits in the reward processing circuitry associated with exposure to early adversity. While in these studies, small samples of individuals exposed to severe childhood adversity (maltreatment, deprivation) were investigated, the present study extends these findings to a substantially larger number of individuals from an epidemiological cohort study who experienced low to moderate levels of adversity. Moreover, in contrast to these studies, which included maltreated individuals with a current psychiatric disorder, the present analysis focused on currently healthy individuals only. The observed activation of the VS, the putamen and the thalamus is in accordance with previous research, supporting the assumption of a specific reward circuitry affected by stress in early life , . Interestingly, while Dillon et al.  reported less activation for maltreated individuals in the left pallidum and putamen, we replicated this effect for the putamen and, additionally, for the thalamus and the VS, the latter serving as the core region of reward processing. The prominent role of the thalamus in the reward circuit has recently been established by the demonstration of a strong direct link to the nucleus accumbens in studies measuring effective connectivity using dynamic causal modeling , .
The finding that neural activity in reward-related areas increased with the level of early adversity during reward delivery is in contrast to previous studies , , which were unable to establish an effect of adversity on the processing of reward outcomes. Several reasons may account for this inconsistency: First, given our substantially larger sample, the present study had a considerably higher power to uncover effects of adversity. Second, a continuous, prospective measure of adversity such as applied in this study may enable the detection of subtle adversity-modulated reward activation in contrast to a case-control design. Third, differences in the MID tasks used to assess reward processing may contribute to the discrepant findings. While in our study, monetary reward was contrasted with verbal reward as a control condition, others included a loss condition or used different intensities of monetary reward as contrasts , . This reduces the number of trials per condition and, in combination with small sample sizes, may lead to reduced effect sizes and less sensitivity to reward outcome. 041b061a72