Biology subjects

Cox, S. M.

Publications and source records attributed to Cox, S. M..

5 recordsLinked to original sources

bioRxiv2025

Inter-individual variability of neurotransmitter receptor and transporter density in the human brain

Neurotransmitter receptors guide the propagation of signals between brain regions. Mapping receptor distributions in the brain is therefore necessary for understanding how neurotransmitter systems mediate the link between brain structure and function. Normative receptor density can be estimated using group averages from Positron Emission Tomography (PET) imaging. However, the generalizability and reliability of group-average receptor maps depends on the inter-individual variability of receptor density, which is currently unknown. Here we collect group standard deviation brain maps of PET-estimated protein abundance for 12 different neurotransmitter receptors and transporters across 7 neurotransmitter systems, including dopamine, serotonin, acetylcholine, glutamate, GABA, cannabinoid, and opioid. We illustrate how cortical and subcortical inter-individual variability of receptor and transporter density varies across brain regions and across neurotransmitter systems. We complement inter-individual variability with inter-regional variability, and show that receptors that vary more across brain regions than across individuals also demonstrate greater out-of-sample spatial consistency. Altogether, this work quantifies how receptor systems vary in healthy individuals, and provides a means of assessing the generalizability of PET-derived receptor density quantification.

neuroscience↗

bioRxiv2022

Multimodal, multiscale connectivity blueprints of the cerebral cortex

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all represent brain connectivity, a comprehensive study of how all these connectivity modes jointly reflect brain structure and function remains missing. Here we systematically integrate seven multimodal, multiscale brain connectivity profiles derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology. We uncover a compact set of universal organizational principles through which brain geometry and neuroanatomy shape emergent connectivity modes. Connectivity modes also exhibit unique and diverse connection patterns, hub profiles, dominant gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes--namely correlated gene expression and receptor similarity--that map well onto multiple phenomena including the rich club and patterns of cortical abnormalities across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, we fuse all seven connectivity modes into a single multimodal network and show that it maps onto major organizational features of the brain including structural conenctivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to next-generation connectomics and the integrative study of inter-regional relationships.

neuroscience↗

bioRxiv2021

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from >1 200 healthy individuals to construct a whole-brain 3-D normative atlas of 19 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

neuroscience↗

bioRxiv2020

Further evidence against a force-velocity trade-off in muscle driven dynamic lever systems

Here we argue that quasi-static analyses are insufficient to predict the speed of an organism from its skeletal mechanics alone (i.e. lever arm mechanics). Using a musculoskeletal numerical model we specifically demonstrate that 1) a single lever morphology can produce a range of output velocities, and 2) a single output velocity can be produced by a drastically different set of lever morphologies. These two sets of simulations quantitatively demonstrate that it is incorrect to assume a one-to-one relationship between lever arm morphology and organism maximum velocity. We then use a statistical analysis to quantify what parameters are determining output velocity, and find that muscle physiology, geometry, and limb mass are all extremely important. Lastly we argue that the functional output of a simple lever is dependent on the dynamic interaction of two opposing factors: those decreasing velocity at low mechanical advantage (low torque and muscle work) and those decreasing velocity at high mechanical advantage (muscle force-velocity effects). These dynamic effects are not accounted for in static analyses and are inconsistent with a force-velocity tradeoff in lever systems. Therefore, we advocate for a dynamic, integrative approach that takes these factors into account when analyzing changes in skeletal levers.

zoology↗

bioRxiv2019

The interaction of compliance and activation on the force-length operating range and force generating capacity of skeletal muscle

Muscle performance is influenced by where it operates on its force-length curve. Here we explore how activation and tendon compliance interact to influence muscle operating lengths and force-generating capacity. To study this, we built a musculoskeletal model of the lower limb of the guinea fowl and simulated the force-length operating range during fixed-end fixed-posture contractions for 39 actuators under thousands of combinations of activation and posture using three different muscle models: Muscles with non-compliant tendons, muscles with compliant tendons but no activation dependent shift in optimal fiber length (L0), and muscles with both compliant tendons and activation-dependent shifts in L0. We found that activation dependent effects altered muscle fiber lengths up to 40% and increased or decreased force capacity by up to 50% during fixed-end contractions. Typically, activation-compliance effects reduce muscle force and are dominated by the effects of tendon compliance at high activations. At low activation, however, activation-dependent shifts in L0 are equally important and can result in relative force changes for low compliance muscles of up to 60%. There are regions of the force-length curve in which muscles are most sensitive to compliance and there are troughs of influence where these factors have little effect. These regions are hard to predict, though, because the magnitude and location of these areas of high and low sensitivity shift with compliance level. Here we provide a map for when these effects will meaningfully influence force capacity and an example of their contributions to force production during a static task, namely standing.

physiology↗