Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood.

Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.

Exploration versus exploitation decisions in the human brain: A systematic review of functional neuroimaging and neuropsychological studies.

Thoughts and actions are often driven by a decision to either explore new avenues with unknown outcomes, or to exploit known options with predictable outcomes. Yet, the neural mechanisms underlying this exploration-exploitation trade-off in humans remain poorly understood. This is attributable to variability in the operationalization of exploration and exploitation as psychological constructs, as well as the heterogeneity of experimental protocols and paradigms used to study these choice behaviours. To address this gap, here we present a comprehensive review of the literature to investigate the neural basis of explore-exploit decision-making in humans. We first conducted a systematic review of functional magnetic resonance imaging (fMRI) studies of exploration-versus exploitation-based decision-making in healthy adult humans during foraging, reinforcement learning, and information search. Eleven fMRI studies met inclusion criterion for this review. Adopting a network neuroscience framework, synthesis of the findings across these studies revealed that exploration-based choice was associated with the engagement of attentional, control, and salience networks. In contrast, exploitation-based choice was associated with engagement of default network brain regions. We interpret these results in the context of a network architecture that supports the flexible switching between externally and internally directed cognitive processes, necessary for adaptive, goal-directed behaviour. To further investigate potential neural mechanisms underlying the exploration-exploitation trade-off we next surveyed studies involving neurodevelopmental, neuropsychological, and neuropsychiatric disorders, as well as lifespan development, and neurodegenerative diseases. We observed striking differences in patterns of explore-exploit decision-making across these populations, again suggesting that these two decision-making modes are supported by independent neural circuits. Taken together, our review highlights the need for precision-mapping of the neural circuitry and behavioural correlates associated with exploration and exploitation in humans. Characterizing exploration versus exploitation decision-making biases may offer a novel, trans-diagnostic approach to assessment, surveillance, and intervention for cognitive decline and dysfunction in normal development and clinical populations.

The neural bases of familiar music listening in healthy individuals: An activation likelihood estimation meta-analysis.

Accumulating evidence suggests that the neural activations during music listening differs as a function of familiarity with the excerpts. However, the implicated brain areas are unclear. After an extensive literature search, we conducted an Activation Likelihood Estimation analysis on 23 neuroimaging studies (232 foci, 364 participants) to identify consistently activated brain regions when healthy adults listen to familiar music, compared to unfamiliar music or an equivalent condition. The results revealed a left cortical-subcortical co-activation pattern comprising three significant clusters localized to the supplementary motor areas (BA 6), inferior frontal gyrus (IFG, BA 44), and the claustrum/insula. Our results are discussed in a predictive coding framework, whereby temporal expectancies and familiarity may drive motor activations, despite any overt movement. Though conventionally associated with syntactic violation, our observed activation in the IFG may support a recent proposal of its involvement in a network that subserves both violation and prediction. Finally, the claustrum/insula plays an integral role in auditory processing, functioning as a hub that integrates sensory and limbic information to (sub)cortical structures.