Cognitive Fluctuations in a Rare Disease Population: Leveraging Cognitive and Speech Ecological Momentary Assessment in Individuals with Phenylketonuria.

Background: Phenylketonuria (PKU) is a rare, hereditary disease that causes disruption in phenylalanine (Phe) metabolism. Despite early intervention, individuals with PKU may have difficulty in several different cognitive domains, including verbal fluency, processing speed, and executive functioning.

Objective: The overarching goal of the Evaluating Fluctuations in Cognitive and Speech Characteristics in Phenylketonuria study (CSP Study) is to characterize the relationships among cognition, speech, mood, and blood-based biomarkers (Phe, Tyr) in individuals with early treated PKU.

Dorsolateral Prefrontal Cortex Enables Updating of Established Memories.

Updating established memories in light of new information is fundamental for memory to guide future behavior. However, little is known about the brain mechanisms by which existing memories can be updated. Here, we combined functional magnetic resonance imaging and multivariate representational similarity analysis to elucidate the neural mechanisms underlying the updating of consolidated memories.

Stress affects the neural ensemble for integrating new information and prior knowledge.

Prior knowledge, represented as a schema, facilitates memory encoding. This schema-related learning is assumed to rely on the medial prefrontal cortex (mPFC) that rapidly integrates new information into the schema, whereas schema-incongruent or novel information is encoded by the hippocampus. Stress is a powerful modulator of prefrontal and hippocampal functioning and first studies suggest a stress-induced deficit of schema-related learning.

Stress leads to aberrant hippocampal involvement when processing schema-related information.

Prior knowledge, represented as a mental schema, has critical impact on how we organize, interpret, and process incoming information. Recent findings indicate that the use of an existing schema is coordinated by the medial prefrontal cortex (mPFC), communicating with parietal areas. The hippocampus, however, is crucial for encoding schema-unrelated information but not for schema-related information.

Cortisol boosts risky decision-making behavior in men but not in women.

Acute stress may escalate risky decision-making in men, while there is no such effect in women. Although first evidence links these gender-specific effects of stress to stress-induced changes in cortisol, whether elevated cortisol is indeed sufficient to boost risk-taking, whether a potential cortisol effect depends on simultaneous noradrenergic activation, and whether cortisol and noradrenergic activation exert distinct effects on risk-taking in men and women is unknown. In this experiment, we therefore set out to elucidate the impact of cortisol and noradrenergic stimulation on risky decision-making in men and women.

Noradrenergic Stimulation Impairs Memory Generalization in Women.

Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization.

Impact of Stress and Glucocorticoids on Schema-Based Learning.

Pre-existing knowledge, a 'schema', facilitates the encoding, consolidation, and retrieval of schema-relevant information. Such schema-based memory is key to every form of education and provides intriguing insights into the integration of new information and prior knowledge. Stress is known to have a critical impact on memory processes, mainly through the action of glucocorticoids and catecholamines.