Biology subjects

Wahlin, A.

Publications and source records attributed to Wahlin, A..

3 recordsLinked to original sources

bioRxiv2025

fMRI-Based CSF Flow Quantification Identifies Cardiac Pulsatility as the Dominant Driver Over Respiratory and Slow Vasomotion Cycles

PurposeCerebrospinal fluid (CSF) flow oscillations have emerged as a potentially important marker related to brain clearance, but their acquisition often relies on specialized imaging MRI sequences. The purpose of this work was to enable quantitative assessment of CSF flow associated with cardiac, respiratory, and slow-vasomotion cycles using widely available functional magnetic resonance imaging (fMRI) acquisitions. MethodsA method was developed to translate fMRI-derived CSF inflow signals into quantitative flow rates. This approach modelled the spin-history of an oscillating ensemble of molecules. Validation was performed using phantom experiments with oscillatory flow at cardiac-, respiratory-, and slow-vasomotion-like frequencies. The method was further applied to resting-state data from 48 older adults (68-82 years; 19 women) to characterize CSF flow at the foramen magnum. ResultsPhantom experiments demonstrated excellent correlations between estimated and true velocities for cardiac- and respiratory-like frequencies (r = 0.94 and 0.97, respectively) and moderate correlation for a slow-vasomotion-like frequency (r = 0.58). In the population cohort, median CSF stroke volumes were 0.86 [0.61, 1.17] mL for the cardiac cycle, 0.44 [0.25, 0.94] mL for the respiratory cycle, and 0.28 [0.14, 0.45] mL for the slow-vasomotion cycle. ConclusionThe proposed spin-history modeling method enabled quantitative estimation of CSF flow components using a conventional fMRI dataset and showed that the cardiac cycle dominates CSF motion at the foramen magnum.

neuroscience↗

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↗

bioRxiv2022

Dynamic regulation of neural variability during working memory reflects dopamine, functional integration, and decision-making

The regulation of moment-to-moment neural variability may permit effective responses to changing cognitive demands. However, the mechanisms that support variability regulation are unknown. In the context of working memory, we leverage the largest available PET and fMRI dataset to jointly consider three lenses through which neural variability regulation could be understood: dopamine capacity, network-level functional integration, and flexible decision processes. We show that with greater working memory load, upregulation of variability was associated with elevated dopamine capacity and heightened functional integration, effects dominantly expressed in the striato-thalamic system rather than cortex. Strikingly, behavioral modeling revealed that working memory load evoked substantial decision biases during evidence accumulation, and those who jointly expressed a more optimal decision bias and higher dopamine capacity were most likely to upregulate striato-thalamic variability under load. We argue that the ability to align striato-thalamic variability to level of demand may be a hallmark of a well-functioning brain.

neuroscience↗