The impact of early life unpredictability on reward processing, learning, and memory

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PROJECT SUMMARY Adverse early life experiences can have remarkably enduring negative consequences on mental health, with numerous, varied psychiatric conditions sharing this developmental origin. Yet, the mechanisms linking adverse experiences to these conditions remain poorly understood. One complication that impedes progress in this area is that prior work has often aggregated over many distinct aspects of adversity, potentially creating a barrier to identifying specific mechanisms for therapeutic intervention. The proposed research addresses this gap by focusing on one particular dimension of early life adversity – caregiver unpredictability — aiming to understand how neural systems may rationally adapt in response to this adversity, and the neuro- computational consequences of this adaptation. We have proposed a computational model that demonstrates how neural systems that follow statistically-optimal adaptation principles can, when faced with an unpredictable early life environment, produce impaired reward learning, diminished expectation of reward, and memory deficits – all of which are previously identified outcomes of early-life unpredictability, and are also common symptoms of psychiatric conditions associated with early-life unpredictability. Translating the model into its hypothesized neurobiological underpinnings generates novel predictions regarding how early-life unpredictability should alter interactions between reward and memory systems. Namely, we predict that early- life unpredictability will alter reward’s effect on core mnemonic computations (pattern completion and separation), and that this will in turn affect how memory guides decisions for reward. We will directly test these predictions across two experiments using a multi-pronged approach integrating computational modeling of behavior with high-resolution functional neuroimaging of medial temporal lobe substructures and their coactivation with reward regions. In doing so, we aim to precisely identify how early-life unpredictability alters reciprocal interactions between reward and memory. In Aim 1, we will determine how early-life unpredictability shapes the influence of reward on memory. In Aim 2, we will determine the impact of early-life unpredictability on memory-guided decisions for reward. Findings from the proposed studies will determine whether behavioral deficits in reward processing and memory following early-life unpredictability can be understood as the consequence of rational adaptation to the structure and statistics of the early life environment.