Biology subjects

Pedersen, R.

Publications and source records attributed to Pedersen, R..

7 recordsLinked to original sources

bioRxiv2025

Compression of functional gradients from rest to naturalistic processing: Moderation effect of age

The functional cortical hierarchy of the human brain, a fundamental principle of brain organization, has been extensively characterized during resting state for healthy younger adults. However, functional re-organization during naturalistic settings, such as movie-watching, and its alterations across the adult lifespan remains poorly understood. Using resting-state and movie fMRI data from two large datasets, Cam-CAN (N=416) and DyNAMiC (N=156), this study conducted a comprehensive comparison of brain organization across two states. We identified a robust reorganization with compression of functional gradients from rest to movie-watching states, which is mediated by changes in functional integration and segregation of brain networks. The extent of compression from rest to movie was significantly greater in older adults and predicted worse cognitive performance among the elderly population. Our findings provide novel insights into how macroscale brain hierarchy is reorganized during naturalistic processing, and how this reorganization during aging impacts cognitive processes, offering a deeper understanding of the neural basis of aging and cognition.

neuroscience↗

bioRxiv2024

Brain-Cognitive Gaps in relation to Dopamine and Health-related Factors: Insights from AI-Driven Functional Connectome Predictions

A key question in human neuroscience is to understand how individual differences in brain function relate to cognitive differences. However, the optimal condition of brain function to study between-person differences in cognition remains unclear. While many studies have developed objective biomarkers to accurately predict intelligence and general cognition, consensus on domain-specific markers has not yet emerged. Brain age has been proposed as a potential candidate, but recent research suggests that brain age offers minimal additional information on cognitive decline beyond what chronological age provides, prompting a shift toward approaches focused directly on cognitive prediction. Using a deep learning approach, we evaluated the predictive power of the functional connectome during various states (resting state, movie-watching, and n-back) on episodic memory and working memory performance. Our findings show that while connectomes during task, especially during movie watching, better predict both episodic and working memory, resting state connectomes are equally effective in predicting episodic memory. Furthermore, individuals with a negative brain-cognition gap (where brain predictions underestimate actual performance) exhibited lower physical activity and higher cardiovascular risk compared to those with a positive gap. This shows that knowledge of the brain-cognition gap provides insights into factors contributing to cognitive resilience. Further lower PET-derived measures of dopamine binding were linked to a greater brain-cognition gap, mediated by regional functional variability. Together, our findings highlight the importance of brain state in connectome-based cognitive prediction and introduce the brain cognitive gap as a potentially informative, dopamine-modulated marker of vulnerability to compromise brain function.

neuroscience↗

bioRxiv2024

Dedifferentiation of caudate-cortical connectivity is linked to reduced D1 dopamine receptor availability and poorer memory function in aging

Age-related alterations in cortico-striatal function have been highlighted as an important determinant of declines in flexible, higher-order, cognition in older age. However, the mechanisms underlying such alterations remain poorly understood. Computational accounts propose age-related dopaminergic decreases to impoverish neural gain control, possibly contributing to reduced specificity of cortico-striatal circuits, that are modulated by dopamine, in older age. Using multi-modal neuroimaging data (fMRI, PET) from a large lifespan cohort (n = 180), we assessed the relationship between dopamine D1-like receptors (D1DRs) and cortico-striatal function during rest and an n-back working memory task. The results revealed gradual age-related decreases in the specificity of functional coupling between the centrolateral caudate and cortical association networks during both rest and working memory, which in turn was associated with poorer short and long-term memory performance with older age. Critically, reduced D1DR availability in the caudate and the prefrontal cortex predicted less differentiated caudate-cortical coupling across the lifespan, in part accounting for the age-related declines observed on this metric. These findings provide novel empirical evidence for a key role of dopamine in maintaining functional specialization of cortico-striatal circuits as individuals age, aligning with computational models that propose deficient catecholaminergic neuromodulation to underpin age-related dedifferentiation of brain function.

neuroscience↗

bioRxiv2023

Megafauna diversity and functional declines in Europe from the Last Interglacial (LIG) to the present

Aim: to estimate European megafauna diversity and functional declines in the present compared to the nearest in time modern-analogue climate period prior to the worldwide diffusion of Homo sapiens. Location: Europe. Time period: Last Interglacial (LIG; ca. 127,000 years ago) to present. Major taxa studied: wild, large ([≥]10 kg) terrestrial mammals. Methods: we assessed the distribution of 48 European megafauna species during the LIG using hindcasting modelling and fossil records. Then, we estimated the decline in megafauna community diversity and potential trait-based functional effects from the LIG to the present, accounting for climate differences between the two periods. Results: from the LIG to the present, species richness and community biomass across Europe dropped by 74.3% ({+/-} 9.9% SD) and 96.7% ({+/-} 4.1% SD), respectively. Functional diversity dropped by 59.1% ({+/-} 11.8% SD) for herbivores and by 48.2% ({+/-} 25.0% SD) for carnivores, while trait-informed potential vegetation and meat consumptions dropped by 91.1% ({+/-} 7.4% SD) and 61.2% ({+/-} 17.2% SD), respectively. The loss in megafauna diversity and associated ecological processes were high everywhere, but particularly in western Europe for carnivores and in the East European Plain for herbivores. We found that potential megafauna richness and functional patterns in the two periods were near identical if only climate-driven differences were considered. Main conclusions: severe, size-biased defaunation has degraded megafauna assemblages and megafauna-mediated ecological processes across Europe from the LIG to the present. These patterns cannot be explained by climate differences between the two periods, thus were likely driven by the impact of prehistoric Homo sapiens. The results suggest that the structure of wild ecosystems of the present strongly deviates from the evolutionary norm, notably with decreased functional heterogeneity and decreased fluxes of biogeochemical compounds across the trophic networks, highlighting the importance of ambitious policies of megafauna community restoration to support ecosystems functioning.

ecology↗

bioRxiv2023

Dopamine D1-receptor Organization Contributes to Functional Brain Architecture

Decades of research on functional brain mapping have highlighted the importance of understanding the functional organization of the cerebral cortex. Recent advances have revealed a gradient of functional organization spanning from primary sensory to transmodal cortices. This gradient-like axis of connectivity has been hypothesized to be aligned with regional differences in the density of neuromodulatory receptors. Recent work in non-human primates supports this notion, revealing a gradient of dopamine D1-like receptor (D1DR) density along the cortical hierarchy. Given the importance of dopaminergic modulation for synaptic activity and neural gain, we tested whether D1DRs shares the same organizational principles as brain function in humans, and whether inter-regional relationships in D1 expression modulate functional crosstalk. Using the worlds largest combined dopamine D1DR-PET and MRI database, we provided empirical support for the first time in humans that the landscape of D1DR availability follows a unimodal-transmodal cortical hierarchy, with greater D1DR expression in associative cortical regions. We found an organization of inter-regional D1DR co-expression spanning unimodal to transmodal brain regions, expressing a high spatial correspondence to the principal macroscale gradient of functional connectivity. Critically, we found that individual differences in D1DR density between unimodal and transmodal regions was associated with greater differentiation of default-mode and somatosensory networks. Finally, inter-regional D1DR co-expression was found to modulate couplings within, but not between, functional networks. Together, our results show that D1DR co-expression provides a biomolecular layer to the functional organization of the brain. Significance StatementWe found a high correspondence between the organization of the most abundantly expressed dopamine receptor subtype and a macroscale unimodal-to-transmodal functional gradient. Differences in D1 density between unimodal and transmodal regions were related to the shape of the functional gradient, contributing to greater differentiation of somatomotor and default mode networks. Finally, we observed that the covariance structure of dopamine D1 receptors is associated with the strength of connectivity within functional networks. The discovery of a dopaminergic layer of brain organization represents a crucial first step towards an understanding of how dopamine, with close ties to behavior and neuropsychiatric conditions, potentially contribute to the emergence of functional brain organization.

neuroscience↗

bioRxiv2023

Two long-axis dimensions of hippocampal cortical integration support memory function across the adult lifespan

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e., gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e., increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory - emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.

neuroscience↗

bioRxiv2022

Bi-phasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan

The dopamine (DA) system, particularly D1-like DA receptors (D1DR), declines across the adult life. The functional consequences of reduced D1DR has been hypothesized to vary across life periods, but the precise timing of these periods is unknown. To examine distinct phases in age-related D1DR reductions, we studied 180 healthy adults (90 females, 20-80 years), who underwent D1DR PET assessment using [11C]SCH23390. A bi-phasic pattern of age-related D1DR differences was revealed, with an inflection point at approximately 40 years of age. Notably, D1DR levels before and after the inflection showed opposing relations to neurocognitive functions, in concordance with distinct consequences of D1DR differences during development and in old age. Furthermore, D1DR reductions in later life were linked to age-related cerebrovascular consequences. These results support a distinction between D1DR reductions in early adulthood from those later in life, and suggest less dramatic and more malleable DA losses in aging than previously suggested.

neuroscience↗