Dorothea Hämmerer

Neuromodulation of reward-based learning and decision making in human aging.

In this paper, we review the current literature to highlight relations between age‐associated declines in dopaminergic and serotonergic neuromodulation and adult age differences in adaptive goal‐directed behavior. Specifically, we focus on evidence suggesting that deficits in neuromodulation contribute to older adults’ behavioral disadvantages in learning and decision making. These deficits are particularly pronounced when reward information is uncertain or the task context requires flexible adaptations to changing stimulus–reward contingencies. Moreover, emerging evidence points to age‐related differences in the sensitivity to rewarding and aversive outcomes during learning and decision making if the acquisition of behavior critically depends on outcome processing. These age‐related asymmetries in outcome valuation may be explained by age differences in the interplay of dopaminergic and serotonergic neuromodulation. This hypothesis is based on recent neurocomputational and psychopharmacological approaches, which suggest that dopamine and serotonin serve opponent roles in regulating the balance between approach behavior and inhibitory control. Studying adaptive regulation of behavior across the adult life span may shed new light on how the aging brain changes functionally in response to its diminishing resources.

Life span differences in electrophysiological correlates of monitoring gains and losses during probabilistic reinforcement learning

By recording the feedback-related negativity (FRN) in response to gains and losses, we investigated the contribution of outcome monitoring mechanisms to age-associated differences in probabilistic reinforcement learning. Specifically, we assessed the difference of the monitoring reactions to gains and losses to investigate the monitoring of outcomes according to task-specific goals across the life span. The FRN and the behavioral indicators of learning were measured in a sample of 44 children, 45 adolescents, 46 younger adults, and 44 older adults. The amplitude of the FRN after gains and losses was found to decrease monotonically from childhood to old age. Furthermore, relative to adolescents and younger adults, both children and older adults (a) showed smaller differences between the FRN after losses and the FRN after gains, indicating a less differentiated classification of outcomes on the basis of task-specific goals; (b) needed more trials to learn from choice outcomes, particularly when differences in reward likelihood between the choices were small; and (c) learned less from gains than from losses. We suggest that the relatively greater loss sensitivity among children and older adults may reflect ontogenetic changes in dopaminergic neuromodulation.

An electrophysiological study of response conflict processing across the lifespan: assessing the roles of conflict monitoring, cue utilization, response anticipation, and response suppression.

We recorded Electroencephalograms (EEGs) during a cued Continuous Performance Task (CPT) to investigate lifespan differences in the efficiency of response conflict processing under conditions that put high demands on the ability to suppress a prepotent response. Previous evidence indicates that children and adolescents commit more errors under such conditions than younger adults, whereas older adults are disproportionately slow in responding. We measured event-related potentials (ERPs) in a sample of 45 children, 44 adolescents, 46 younger adults, and 47 older adults to investigate response conflict monitoring (Nogo-N2), cue utilization (Cue-P3), response anticipation (contingent negative variation, CNV), and response suppression (Nogo-P3). In comparison to adolescents and adults, children showed larger ERPs associated with cue utilization. At the same time, children committed more errors and their ERPs reflecting response anticipation and response suppression were smaller and uncorrelated. In contrast, older adults showed ERP indices of attentional distraction (P3a elicited by the infrequent Non-Cue stimuli), reduced conflict monitoring signals (Nogo-N2), and took more time to respond than the other age groups. The present findings reveal marked lifespan differences in processes related to response conflict monitoring. In middle childhood, the readiness to utilize cues for guiding actions is not yet fully matched by the ability to suppress prepotent responses, leading to a relatively large number of commission errors. In older adults, higher indices of attentional distraction as well as lower conflict monitoring signals were observed. This might reflect a dampened build-up of response tendencies, thereby leading to slower responding and relatively low error rates.

Dopaminergic and Prefrontal Contributions to Reward-Based Learning and Outcome Monitoring during Child Development and Aging.

In many instances, children and older adults show similar difficulties in reward-based learning and outcome monitoring. These impairments are most pronounced in situations in which reward is uncertain (e.g., probabilistic reward schedules) and if outcome information is ambiguous (e.g., the relative value of outcomes has to be learned). Furthermore, whereas children show a greater sensitivity to external outcome information, older adults focus less on a rapid differentiation of rewarding outcomes. In this article, we review evidence for the idea that these phenomenologically similar impairments in learning and outcome monitoring in children and older adults can be attributed to deficits in different underlying neurophysiological mechanisms. We propose that in older adults learning impairments are the result of reduced dopaminergic projections to the ventromedial prefrontal cortex, which lead to less differentiated representations of reward value. In contrast, in children, impairments in learning can be primarily attributed to deficits in executive control, which may be due to a protracted development of the dorsal medial and lateral prefrontal cortices. We think that this framework maps well onto recent neurophysiological models of reward processing and is plausible from a broader developmental perspective.

Lower theta inter-trial phase coherence during performance monitoring is related to higher reaction time variability : A lifespan study

Trial-to-trial reaction time (RT) variability is consistently higher in children and older adults than in younger adults. Converging evidence also indicates that higher RT variability is (a) associated with lower behavioral performance on complex cognitive tasks, (b) distinguishes patients with neurological deficits from healthy individuals, and also (c) predicts longitudinal cognitive decline in older adults. However, so far the processes underlying increased RT variability are poorly understood. Previous evidence suggests that control signals in the medial frontal cortex (MFC) are reflected in theta band activity and may implicate the coordination of distinct brain areas during performance monitoring. We hypothesized that greater trial-to-trial variability in theta power during performance monitoring may be associated with greater behavioral variability in response latencies. We analyzed event-related theta oscillations assessed during a cued-Go/NoGo task in a lifespan sample covering the age range from middle childhood to old age. Our results show that theta inter-trial coherence during NoGo trials increases from childhood to early adulthood, and decreases from early adulthood to old age. Moreover, in all age groups, individuals with higher variability in medial frontal stimulus-locked theta oscillations showed higher trial-to-trial RT variability behaviorally. Importantly, this effect was strongest at high performance monitoring demands and independent of motor response execution as well as theta power. Taken together, our findings reveal that lower theta inter-trial coherence is related to greater behavioral variability within and across age groups. These results hint at the possibility that more variable MFC control may be associated with greater performance fluctuations.

A lifespan comparison of the reliability, test-retest stability and signal-to-noise ratio of event-related potentials assessed during performance monitoring

The reliability, stability, and signal-to-noise ratio (SNR) of event-related potentials (ERPs) were investigated in children, adolescents, younger adults, and older adults in performance monitoring tasks. P2, N2, P3, and P2-N2 peak-to-peak amplitude showed high odd-even split reliabilities in all age groups, ranging from.70 to.90. Multigroup analyses showed that test-retest stabilities (across 2 weeks) of ERP amplitudes did not differ among the four age groups. In contrast, relative to adolescents and younger adults, SNRs were lower in children and older adults, with higher noise levels in children and lower signal power in older adults. We conclude that age differences in the SNR of stimulus-locked ERPs can be successfully compensated by the averaging procedure with about 40 trials in the average. However, age differences in baseline noise and split-half reliability should be considered when comparing age groups in single trial measures or time-varying processes with ERPs.

Performance monitoring across the lifespan: Still maturing post-conflict regulation in children and declining task-set monitoring in older adults

Conditions that render the selection of correct actions difficult require the monitoring of the execution and outcomes of ones own actions. Such performance monitoring abilities undergo maturational and aging-related changes across the lifespan. This review highlights evidence for qualitative differences in behavior and physiological correlates of performance monitoring across the lifespan. Few developmental studies examine both stimulus-locked as well as response-locked components. Here, we examine a lifespan pattern of stimulus- as well as response-locked ERPs during performance monitoring to inform age differences in subprocesses of performance monitoring. Findings from functional magnetic resonance imaging (fMRI) studies that lend further support for the observed age differences in performance monitoring are also reviewed. Together, the evidence suggest that suboptimal performance monitoring during maturation is characterized by a reduced ability to flexibly translate experienced conflicts into top-down control, whereas declined performance monitoring in aging is characterized by difficulties in maintaining task set representations. Such age specific deficits are apparent in performance monitoring related to response conflicts as well as in performance monitoring during reinforcement learning and value-based decision making.

Effects of PPP1R1B (DARPP-32) Polymorphism on Feedback-Related Brain Potentials Across the Life Span

Maximizing gains during probabilistic reinforcement learning requires the updating of choice – outcome expectations at the time when the feedback about a specific choice or action is given. Extant theories and evidence suggest that dopaminergic modulation plays a crucial role in reinforcement learning and the updating of choice – outcome expectations. Furthermore, recently a positive component of the event-related potential about 200 ms (P2) after feedback has been suggested to reflect such updating. The efficacy of dopaminergic modulation changes across the life span. However, to date investigations of age-related differences in feedback-related P2 during reinforcement learning are still scarce. The present study thus aims to investigate whether individual differences in the feedback-related P2 would be associated with polymorphic variations in a dopamine relevant gene PPP1R1B (also known as DARPP-32) and whether the genetic effect may differ between age groups. We observed larger P2 amplitudes in individuals carrying the genotype associated with higher dopamine receptor efficacy, i.e., a allele homozygotes of a single nucleotide polymorphism (rs907094) of the PPP1R1B gene. Moreover, this effect was more pronounced in children and older adults in comparison to adolescents and younger adults. Together, our findings indicate that polymorphic variations in a dopamine relevant gene are associated with individual differences in brain-evoked potentials of outcome updating and hint at the possibility that genotype effects on neurocognitive phenotypes may vary as a function of brain maturation and aging.

Selective alteration of human value decisions with medial frontal tDCS is predicted by changes in attractor dynamics

During value-based decision making, ventromedial prefrontal cortex (vmPFC) is thought to support choices by tracking the expected gain from different outcomes via a competition-based process. Using a computational neurostimulation approach we asked how perturbing this region might alter this competition and resulting value decisions. We simulated a perturbation of neural dynamics in a biophysically informed model of decision-making through in silico depolarization at the level of neuronal ensembles. Simulated depolarization increased baseline firing rates of pyramidal neurons, which altered their susceptibility to background noise, and thereby increased choice stochasticity. These behavioural predictions were compared to choice behaviour in healthy participants performing similar value decisions during transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique. We placed the soma depolarizing electrode over medial frontal PFC. In line with model predictions, this intervention resulted in more random choices. By contrast, no such effect was observed when placing the depolarizing electrode over lateral PFC. Using a causal manipulation of ventromedial and lateral prefrontal function, these results provide support for competition-based choice dynamics in human vmPFC, and introduce computational neurostimulation as a mechanistic assay for neurostimulation studies of cognition.