Biology subjects

Hurley, S. A.

Publications and source records attributed to Hurley, S. A..

6 recordsLinked to original sources

bioRxiv2026

Levodopa induced dyskinesia severity is linked to distinct microstructural alterations in nigrostriatal and brainwide neural circuits

Dopaminergic replacement therapy via L-DOPA is the major medical therapy for Parkinsons Disease. Long-term L-DOPA administration is known to cause dyskinetic movements, L-DOPA Induced Dyskinesia (LID). It remains unclear if the LID related, maladaptive changes in brain structure/function are localized to neural circuits within the nigrostriatal DA system or have brainwide impact. We employed multi-shell diffusion magnetic resonance imaging and correlational tractography to investigate structural brain networks associated with daily administration of L-DOPA and the development of LID in the unilateral 6-hydroxydopamine rat model. 53% of rats receiving L-DOPA therapy developed severe LID. Tractography found brainwide statistical maps positively and negatively associated with LID severity highlighted by bilateral neural circuits contained in the lesioned nigrostriatal system as well as others including the cerebellum and prefrontal cortex. These results suggest that systemic dysfuntion in brainwide neural circuits forms the mechanistic basis the maladaptive changes underlying LID.

neuroscience↗

bioRxiv2025

Cellular deconvolution of the brain with topological magnetic resonance image analysis

Magnetic resonance imaging (MRI) is foundational tool in neuroscience, enabling characterization of neuroanatomical markers of disease, behavior, and cognition. However, the precise cellular processes driving the structural and functional readouts provided by MRI remain opaque. Non-invasively assessing cell type, abundance, and location using MRI has the potential to revolutionize both basic science and clinical practice. To this end, we developed SpaTial Representation and Analysis using Topological Architecture (STRATA), an image-based gradient-boosted machine learning framework, which quantifies cell type proportions of neurons, astrocytes, oligodendrocytes, and microglia from MR images. Here we demonstrate and validate STRATA on diverse disease models, species, and regions of interest that together highlight the generalizability of the STRATA framework.

neuroscience↗

bioRxiv2025

Towards Optimizing Target Engagement in Non-Invasive Trigeminal Nerve Stimulation: Anatomical Characterization and Computational Modeling of the Human Trigeminal Nerve

ObjectiveCranial nerve stimulation (CNS) uses electric current to modulate higher-order brain activity and organ function via nerves, including the vagus and trigeminal, with applications in migraine, epilepsy, and pediatric ADHD. The trigeminal nerve is an emerging target for non-invasive neuromodulation due to the superficial trajectory of its branches, the supraorbital (SON), infraorbital (ION), and mental nerves (MN), and the predominantly sensory composition of the SON and ION. However, the parameters and outcomes of trigeminal nerve stimulation (TNS) remain varied. ApproachThis study characterizes the anatomical course, tissue composition, and activation profiles of the SON, ION, and MN using five human donors. CT imaging was utilized to localize each nerves exit foramen and distance to midline. Microdissections quantified nerve circumference and depth relative to the skin surface. Histological analysis described the number of fascicles and fascicular tissue area. Nerve depths were incorporated into computational models to illustrate the activation function across tissue layers, comparing expected nociceptor and nerve trunk activation functions as a measure of neural engagement. Main ResultsThe SON was found to be significantly more superficial than the ION and MN and had a higher nerve-to-connective tissue ratio relative to the MN. Computational modeling demonstrated that the activation function at the depths of nociceptors was orders of magnitude greater than within the main nerve trunks, suggesting preferential recruitment of cutaneous nociceptors, dependent on nociceptor density. SignificanceThe SON presents the most accessible and anatomically favorable target for transcutaneous trigeminal nerve stimulation among the branches examined due to its superficial location. However, preferential activation of low-threshold nociceptors compared to nerve trunks may lead to treatment-limiting off-target side effects, favoring strategies that target fibers of interest within the skin. These findings offer an anatomically informed framework to guide further computational modeling and electrode design for targeted trigeminal neuromodulation.

neuroscience↗

bioRxiv2024

Assessing changes in whole-brain structural connectivity in the unilateral 6-hydroxydopamine rat model of Parkinson's Disease using diffusion imaging and tractography

I.Parkinsons disease (PD) is a multifactorial, progressive neurodegenerative disease that has a profound impact on those it afflicts. Its hallmark pathophysiology is characterized by degeneration of dopaminergic neurons in the midbrain which trigger a host of motor and non- motor symptoms. Many preclinical research efforts utilize unilateral lesion models to assess the neural mechanisms of PD and explore new therapeutic approaches because these models produce similar motor symptoms to those of PD patients. The goal of this work is to examine changes in brain structure resulting from a unilateral lesion both within the nigrostriatal system, where dopaminergic neurons are lost, and throughout the brain. Using multi-shell diffusion magnetic resonance imaging and correlational tractography, we assessed microstructural changes throughout the brain resulting from unilateral injection of 6-hydroxydopamine (6-OHDA) in the median forebrain bundle (MFB). Following lesioning, the PD phenotype was confirmed using behavioral and histological assessment. Correlational tractography found networks of fiber tracts that were either positively or negatively correlated with lesion status throughout the brain. Analyzing patterns of intra- and inter-hemispheric connectivity between the positively and negatively correlated fiber tracts revealed two separate neural networks. The first contained only negatively correlated fibers in the lesioned hemisphere consistent with the local effects of the lesion (i.e. dopaminergic depletion in the nigrostriatal system). The second contained systematically overlapping fiber tracts in the lesioned and non-lesioned hemispheres including the olfactory system and cerebellum, which we suggest are indicative of adaptive mechanisms to compensate for the lesion. Taken together, these results suggest that correlational tractography is a reasonable tool to examine whole brain structural changes in rodent models of neurodegenerative disease, and may have future translational value as a diagnostic tool for patients with PD.

neuroscience↗

bioRxiv2021

Human primary visual cortex shows larger population receptive fields for binocular disparity-defined stimuli

1The visual perception of 3D depth is underpinned by the brains ability to combine signals from the left and right eyes to produce a neural representation of binocular disparity for perception and behavior. Electrophysiological studies of binocular disparity over the past two decades have investigated the computational role of neurons in area V1 for binocular combination, while more recent neuroimaging investigations have focused on identifying specific roles for different extrastriate visual areas in depth perception. Here we investigate the population receptive field properties of neural responses to binocular information in striate and extrastriate cortical visual areas using ultra-high field fMRI. We measured BOLD fMRI responses while participants viewed retinotopic-mapping stimuli defined by different visual properties: contrast, luminance, motion, correlated and anti-correlated stereoscopic disparity. By fitting each condition with a population receptive field model, we compared quantitatively the size of the population receptive field for disparity-specific stimulation. We found larger population receptive fields for disparity compared with contrast and luminance in area V1, the first stage of binocular combination, which likely reflects the binocular integration zone, an interpretation supported by modelling of the binocular energy model. A similar pattern was found in region LOC, where it may reflect the role of disparity as a cue for 3D shape. These findings provide insight into the binocular receptive field properties underlying processing for human stereoscopic vision.

neuroscience↗

bioRxiv2020

A method to remove the influence of fixative concentration on post-mortem T2 maps using a Kinetic Tensor model

Formalin fixation has been shown to substantially reduce T2 estimates when performing post-mortem imaging, primarily driven by the presence of bulk fixative in tissue. Prior to scanning, post-mortem tissue samples are often placed into a fluid that has more favourable imaging properties, such as matched magnetic susceptibility. This study investigates whether there is any evidence for a change in T2 in regions close to the tissue surface in post-mortem T2 maps due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T2 inhomogeneity. To achieve this, T2 maps and diffusion tensor estimates were obtained in 14 whole, formalin fixed post-mortem brains placed in fluorinert approximately 48 hours prior to scanning. This consisted of 7 brains fixed with 10% formalin and 7 brains fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a Kinetic Tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T2 pattern consistent with the modelled fixative outflux. Confound regression of fixative concentration reduced T2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model vs simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations with ferritin and myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between T2 and PLP for the two fixative types after KT correction. Only small correlations were identified between T2 and ferritin before and after KT correction.

neuroscience↗