Biology subjects

Druzgal, T. J.

Publications and source records attributed to Druzgal, T. J..

10 recordsLinked to original sources

bioRxiv2026

Widely Used Calculations of Intracranial Volume Provide Inaccurate Estimates in Developmental Cohorts: Evidence and Solutions for the Neuroimaging Community

Intracranial volume (ICV) is often estimated as part of automated neuroimaging processing pipelines and commonly used to account for and characterize cranial size. FreeSurfer's estimated intracranial volume (eTIV) produces implausible longitudinal estimates in developmental samples when using versions prior to FreeSurfer 8. Across two different adolescent datasets, we document eTIV changes of up to 39% between 1.5 - 2 year sessions for FreeSurfer 7, with errors more pronounced on Siemens scanners and in female participants. These errors are markedly reduced in FreeSurfer 8 and AssemblyNet. However, the widespread use of FreeSurfer 7 raises concern about developmental neuroimaging studies that utilize eTIV without quality control.

neuroscience↗

bioRxiv2025

Structural Determinants of Signal Speed: A Multimodal Investigation of Face Processing in Autism Spectrum Disorder

It has not previously been possible to investigate the fundamental relationship between axonal structure - which dictates action potential transmission - and human neuronal function in vivo. Here, we introduce a novel metric of axonal signal speed, estimated axonal latency (EAL), derived from the relationship between axonal diameter, myelination, and length measured via MRI. We validate EAL along two pathways of the face processing network by relating it to N170 latency, an electrophysiological marker of face processing speed measured via EEG. Our results show that EAL along these pathways predicts N170 latency specifically during face processing. Moreover, we demonstrate that individuals with and without autism rely upon different pathways, potentially providing a structural account for autism-related face processing differences. By establishing this relationship between EEG-based electrical function and MRI-based axonal microstructure, we provide a non-invasive, spatially detailed estimate of neuronal processing speed that can inform our understanding of brain function, development, and disorder. TeaserEstimated axonal latency is a non-invasive, spatially detailed measure of neuronal speed to inform brain function and disorder.

neuroscience↗

bioRxiv2025

The NTU-DSI-122 template as a flexible platform for fiber orientation distribution registration of diffusion microstructure into stereotaxic space

The registration of neuroimaging subjects to a common stereotaxic space allows for comparisons between timepoints, subjects, or with reference atlases of regions of interest. Typically, this has been performed by computing a similarity metric between the voxel-wise intensity values in the subject image and a reference image. Diffusion MRI is a method that provides far more detailed voxel-wise information than a simple scalar intensity value. This allows for the potential to use this additional information to perform registration with added within-tissue contrast. In this study, we present a novel use of the NTU-DSI-122 template as a fiber orientation distribution (FOD) template, for the purpose of registering subject dMRI images to stereotaxic space. The reliability and accuracy of this FOD-based registration method are compared to the intensity-based registration method ANTs by registering cellular microstructure maps from two separate cohorts to the NTU-DSI-122 template. The stochastic FOD-based method significantly outperformed the stochastic intensity-based metric on reliability and was able to more consistently register the same subject multiple times independently. The FOD-based method also significantly outperformed the intensity-based metric on registration accuracy by more completely aligning the microstructure maps to the template as measured by the Sorenson-Dice coefficient at multiple percentile thresholds. The NTU-DSI-122 template has the additional benefit of including multiple b-value shells between a wide range of feasible acquisition schemes, making the platform a flexible option for registering acquisitions of varying quality, including clinically acquired data.

neuroscience↗

bioRxiv2025

Diffusion MRI microstructure markers of changes in the human brain across the lifespan

Understanding how the brain develops, matures, ages, and declines is one of the fundamental questions facing neuroscience. Recent advances in diffusion MRI microstructure analysis have allowed for detailed descriptions of neuronal change in humans. However, it is essential that findings from these studies are appropriately contextualized to general age-related changes in the brain. This study uses 3-tissue constrained spherical deconvolution (3T-CSD) to examine the relationship between brain diffusion microstructure and chronological age. 3T-CSD is able to quantify signal fraction measurements at the voxel-wise level from three different tissue microenvironments found in the brain: extracellular free water, intracellular isotropic, and intracellular anisotropic. This study applies 3T-CSD analysis to the Nathanial Kline Institutes Rockland cohort, a large-scale community sample of brain MRI data across the lifespan. Microstructural measurements were taken in a number of structures throughout the white matter, subcortical gray matter, and lobar cortical regions while additionally evaluating lateral differences in microstructural measurements. The general trajectory of signal fraction measurements was a positive relationship with age and extracellular signal fraction, a negative relationship between age and intracellular isotropic signal fraction, and an inverted U-shaped trajectory for the intracellular anisotropic signal fraction. In individual sub-areas these trends tended to still be present, with some notable exceptions. However there were large differences in 3T-CSD microstructure measurements between individual structures, including significant lateral differences between hemispheres for each of the subcortical gray matter structures and for each of the cortical regions. These results demonstrate that 3T-CSD is able to describe age-related change across the brain and lifespan. By using a healthy population cohort this study can be used as a point of comparison for 3T-CSD analysis of microstructure changes in the presence of pathology. Finally, the detailed analysis of lateralized ROI results can inform diffusion microstructure studies examining cortical and subcortical regions.

neuroscience↗

bioRxiv2024

Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, this study aims to first associate a broad array of behavioral metrics with neuroimaging markers of ASD, and to explore the prevalence of ASD subtypes using a neuroimaging driven perspective. Analyzing 273 participants (148 with ASD) ages 8 to 17 through an NIH-sponsored Autism Centers of Excellence network (MH100028), we observe widespread associations between behavioral and cognitive evaluations of autism and between behavioral and microstructural metrics, alongside different directional correlations between different behavioral metrics. Stronger associations with individual subcategories from each test rather than summary scores suggest that different neuronal profiles may be masked by composite test scores. Machine learning cluster analyses applied to neuroimaging data reinforce the association between neuroimaging and behavioral metrics and suggest that age-related maturation of brain metrics may drive changes in ASD behavior. This suggests that if ASD can be definitively subtyped, these subtypes may show different behavioral trajectories across the developmental period. Clustering identified a pattern of restrictive and repetitive behavior in some participants and a second group that was defined by high sensory sensitivity and language performance.

neuroscience↗

bioRxiv2023

Developmental Ramifications of the Screen Age: Associations between Screen Time and Neural Maturation in a Massive Adolescent Cohort

A growing body of literature associates increases in electronic screen time with a vast array of psychological consequences amongst adolescents, but little is known about the neurological underpinnings of this relationship. This longitudinal study examines structural and diffusion brain MRI scans from the Adolescent Brain Cognitive Development (ABCD)Study: a large multi-site study with thousands of participants. By assessing both gray matter density (GMD) and grey matter measurements of diffusion microstructure in the adolescent brain, we describe how the developmental trajectory of the brain changes with screen-based media consumption at the sub-cellular level. Grey matter microstructure was measured across 13 bilateral regions functionally implicated with screen time use, and associated with either the control or reward system. After controlling for age, sex, total brain volume, scanning site, sibling relationships, physical activity, and socioeconomic status, this study finds significant positive correlations between increased screen time and axonal signal across 6 of the 13 regions while also finding significantly decreased intracellular signal in 8 regions. Comparing these associations to normal developmental trajectories suggests adolescent age-related brain development may be accelerated by increased screen time in brain areas associated with reward processing while age-related brain development may be decelerated in regions of the control system. Highlighting the sensitivity of microstructural analysis, no significant cross-sectional or longitudinal relationship with increased screen time was found using GMD, or fractional anisotropy. This work suggests that increased screen usage during adolescent development has a complex association with brain tissue that cannot be completely described by traditional quantifications of tissue microstructure.

neuroscience↗

bioRxiv2023

Conduction Velocity, G-ratio, and Extracellular Water as Microstructural Characteristics of Autism Spectrum Disorder

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a novel metric termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel neuroimaging metric, aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

neuroscience↗

bioRxiv2022

More than just axons: A positive relationship between an intracellular isotropic diffusion signal and pubertal development in white matter regions in a massive adolescent cohort

Puberty is a key event in adolescent development that involves significant, hormone-driven changes to many aspects of physiology including the brain. Understanding how the brain responds during this time period is important for evaluating neuronal developments that affect mental health throughout adolescence and the adult lifespan. This study examines diffusion MRI scans from the cross-sectional ABCD Study baseline cohort, a large multi-site study containing thousands of participants, to describe the relationship between pubertal development and brain microstructure. Using advanced, 3-tissue constrained spherical deconvolution methods, this study is able to describe multiple tissue compartments beyond only white matter (WM) axonal qualities. After controlling for age, sex, brain volume, subject handedness, scanning site, and sibling relationships, we observe a positive relationship between an isotropic, intracellular diffusion signal fraction and pubertal development across a majority of regions of interest (ROIs) in the WM skeleton. We also observe regional effects from an intracellular anisotropic signal fraction compartment and extracellular isotropic free water-like compartment in several ROIs. This work suggests that changes during pubertal development elicit a complex response from brain tissue that cannot be completely described by traditional methods focusing only on WM axonal properties. This work brings in vivo human neuroimaging studies more into line with work performed on animal models, which describe an interaction between increased myelination, neurogenesis, angiogenesis, and glial cell proliferation in response to pubertal hormones.

neuroscience↗

bioRxiv2022

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. Given the blood plasma correlations used to develop GrimAge, a specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individuals brain affected by their unique white matter hyperintensity location and volume. 98 subjects over 55 years of age were scanned at baseline with 41 returning for a follow-up scan 2 years later. Using diffusion MRI lesionometry, we reconstructed subject-specific networks of affected axonal tracts and examined the diffusion cellular microstructure composition of these areas, both at baseline and longitudinally, for evidence of cellular degeneration. A chronological age-adjusted version of GrimAge was significantly correlated with baseline WMH volume and markers of neuronal decline, indicated by increased extracellular free water, increased intracellular signal, and decreased axonal signal within WMH. By isolating subject-specific axonal regions lesioned by crossing through a WMH, age-adjusted GrimAge was also able to predict longitudinal development of similar patterns of neuronal decline throughout the brain. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.

neuroscience↗

bioRxiv2019

Test-retest reliability and long-term stability of 3-tissue constrained spherical deconvolution methods for analyzing diffusion MRI data

PurposeSeveral recent studies have utilized a 3-tissue constrained spherical deconvolution pipeline to obtain quantitative metrics of brain tissue microstructure from diffusion-weighted MRI data. The three tissue compartments, comprising white matter-, grey matter-, and CSF-like (free water) signals, are potentially useful in the evaluation of brain microstructure in a range of pathologies. However, the reliability and long-term stability of these metrics has not yet been evaluated.\n\nMethodsThis study examined estimates of whole brain microstructure for the three tissue compartments, in three separate test-retest cohorts. Each cohort has different lengths of time between baseline and retest, ranging from within the same scanning session in the shortest interval to three months in the longest interval. Each cohort was also collected with different acquisition parameters.\n\nResultsThe CSF-like compartment displayed the greatest reliability across all cohorts, with intraclass correlation coefficient (ICC) values being above 0.95 in each cohort. White matter-like and grey matter-like compartments both demonstrated very high reliability in the immediate cohort (both ICC>0.90), however this declined in the 3 month interval cohort to both compartments having ICC>0.80. Regional CSF-like signal fraction was examined in bilateral hippocampus and had an ICC>0.80 in each cohort.\n\nConclusionThe 3-tissue CSD techniques provide reliable and stable estimates of tissue microstructure composition, up to 3 months longitudinally in a control population. This forms an important basis for further investigations utilizing 3-tissue CSD techniques to track changes in microstructure across a variety of brain pathologies.

neuroscience↗