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Turner, G. R.

Publications and source records attributed to Turner, G. R..

8 recordsLinked to original sources

Novelty-seeking and directed exploration scale with dissociable social network outcomes and brain systems in older adults

Social isolation and loneliness are major determinants of well-being in older adults. Shrinking social networks and age-related shifts in social behavior and decision-making may increase vulnerability to loneliness. These changes in social decision-making strategies can be conceptualized within an exploration-exploitation tradeoff framework, in which social options with known outcomes are prioritized over uncertain ones. Yet, no study has characterized how complementary decision-making strategies, undirected novelty seeking and goal-directed exploration, relate to social network constructs or are supported by distinct neural systems. These strategies capture distinct forms of decision-making: undirected novelty seeking is driven by the intrinsic salience of novel options independent of expected informational gain, whereas goal-directed exploration involves deliberately sampling uncertain options to reduce uncertainty and optimize future choices. Here, we used fMRI and a novel social bandit reinforcement task to identify dissociable social constructs and brain systems linked to undirected novelty seeking and goal-directed exploration in older adults. Undirected novelty seeking was associated with social network size and with activity of temporoparietal and mid-cingulate brain areas. Goal-directed exploration predicted subjective feelings of social connectedness and was associated with activity of anterior cingulate and prefrontal brain areas. Crucially, choice probabilities from a non-social version of the three-arm bandit task were not associated with social decision-making nor with social constructs. Our findings suggest that, in later life, dissociable social decision-making strategies, when faced with unknown options, rely on distinct neural systems supporting social network size as well as subjective feelings of social connectedness.

neuroscience↗

Longitudinal changes in control energy of brain networks in older adults at familial risk for Alzheimers disease

The ability of structural brain networks to control neural dynamics is affected by healthy and pathological aging, including Alzheimers disease (AD). According to network control theory, transitions between functional brain states incur energetic costs. How these costs change longitudinally with aging remains unknown. Here, in 279 older adults at familial risk for AD, control energy increased longitudinally for state maintenance and transitions between sensorimotor and attentional networks, while decreasing for another sensorimotor--attentional transition. Changes in transition costs between higher-order networks were associated with cognitive performance: greater DorsAttn--Executive cost was associated with poorer immediate memory, while lower Executive--Def+Lim cost was associated with poorer attention. Higher plasma p-tau181 was associated with lower DorsAttn--Def+Lim transition cost. These findings reveal transition-specific alterations in the energetic landscape of aging and distinct relationships with cognition and AD pathology. Together, they highlight energetic constraints on brain network reconfiguration as a complementary perspective on neurocognitive aging.

neuroscience↗

Thalamocortical orchestration of human theory of mind

Reasoning about others thoughts or beliefs is central to human social behavior. This ability, known as theory of mind (ToM), has been primarily attributed to cortical regions of the default network (DN). However, whether and how subcortical structures, particularly the thalamus, contribute to this high-level computation remains unknown. Here, we investigated human thalamocortical dynamics during a naturalistic ToM movie watching condition, taking a rare dual-modality approach by combining high-field 7T fMRI and intracranial stereoelectroencephalography (sEEG). Across both modalities, ToM events reliably activated the DN, whereas the thalamus lacked canonical local activation. Despite this absence of local activation, the thalamus shared ToM-related representational structure and exhibited enhanced bidirectional interactions with the DN during mentalizing across methods. Crucially, sEEG revealed that the thalamus coordinated DN activity via cross-frequency phase-amplitude coupling (PAC), whereby thalamic low-frequency phase unidirectionally modulated DN high-frequency activity. Furthermore, the strength of thalamic-DN PAC predicted both the activity magnitude and the representational quality of ToM-related information within the dorsomedial DN subsystem. Together, these findings identify the human thalamus as a regulatory hub that gates DN computations during ToM without exhibiting observable localized activity, revealing a previously unrecognized mechanism by which thalamic dynamics coordinate high-level social cognition in humans.

neuroscience↗

Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease

INTRODUCTIONThe locus coeruleus (LC) is among the first sites of tau pathology in Alzheimers disease (AD) and may seed neocortical tau. METHODSWe used longitudinal neuromelanin-sensitive MRI to assess LC integrity in vivo in a cohort of cognitively unimpaired older adults with familial risk of AD in relation to tau and amyloid PET and long-term cognitive trajectories. RESULTSWe showed that both LC integrity at baseline and its rate of degeneration over time independently predicted a neocortical pattern of tau deposition. In keeping with the known function of the LC, neuropsychological tests showed that LC integrity at baseline predicted changes in attention. Finally, we found that longitudinal LC degeneration correlated with memory decline in people with elevated neocortical amyloid burden. DISCUSSIONOur findings underscore the importance of LC in AD pathogenesis. Longitudinal measurement of LC degeneration may help distinguish trajectories of age-related cognitive decline and early AD.

neuroscience↗

Cholinergic synaptic plasticity shapes resilience and vulnerability to tau

Synaptic dysfunction is a hallmark of Alzheimers disease (AD). Yet due to their plasticity, synapses may also adapt to early AD pathology. Here, we demonstrate that cholinergic neurons mount a presynaptic response to tau pathology in the living human brain. Using multi-tracer positron emission tomography in cognitively normal older adults at risk for AD, we observe that cholinergic neurons increase presynaptic vesicular acetylcholine transporter (VAChT) protein levels when colocalized to tau, but not amyloid. Notably, stronger VAChT responses were associated with cognitive resilience over a decade. Whole-brain single-nucleus RNA sequencing in human and mouse tissue reveal that cholinergic neurons are enriched for a plasticity gene-network anchored to the microtubule-associated protein tau (MAPT) gene. In mice, forebrain-specific deletion of VAChT impairs cortical plasticity and hippocampal structural integrity. Overall, our findings identify cholinergic synaptic plasticity, and its failure, as a fundamental mechanism of resilience and vulnerability to tau in presymptomatic AD.

neuroscience↗

The biological role of local and global fMRI BOLD signal variability in human brain organization

Variability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have yet been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.

neuroscience↗

Taking stock of the past: A psychometric evaluation of the Autobiographical Interview

Autobiographical memory (AM) involves a rich phenomenological re-experiencing of a spatio-temporal event from the past, which is challenging to objectively quantify. The Autobiographical Interview (AI; Levine et al., 2002, Psychology & Aging) is a manualized performance-based assessment designed to quantify episodic (internal) and semantic (external) features of recalled and verbally conveyed prior experiences. The AI has been widely adopted yet has not undergone a comprehensive psychometric validation. We investigated the reliability, validity, association to individual differences measures, and factor structure in healthy younger and older adults (N=352). Evidence for the AIs reliability was strong: the subjective scoring protocol showed high inter-rater reliability and previously identified age effects were replicated. Internal consistency across timepoints was robust, suggesting stability in recollection. Central to our validation, internal AI scores were positively correlated with standard, performance-based measures of episodic memory, demonstrating convergent validity. The two-factor structure for the AI was not well-supported by confirmatory factor analysis. Adjusting internal and external detail scores for the number of words spoken (detail density) improved trait estimation of AM performance. Overall, the AI demonstrated sound psychometric properties for inquiry into the qualities of autobiographical remembering.

neuroscience↗

Functional architecture of the aging brain

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience dependent changes, or both, is uncertain. We employed a multi-method strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n=181) and older (n=120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant, while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multi-scale, multi-method approaches to characterize the architecture of functional brain aging.

neuroscience↗