Biology subjects

Van, A. N.

Publications and source records attributed to Van, A. N..

14 recordsLinked to original sources

bioRxiv2025

Patterns of brain-wide associations reflect socioeconomics

Previous brain-wide association studies (BWAS) cross-sectionally linked a specific behavioral trait, most commonly IQ or psychopathology, to variation in brain function or structure. Here, we expanded the focus of BWAS from effect sizes to interpretability and generalizability by mapping 649 variables to brain function and structure. We compared the resultant BWAS maps to other types of brain data to annotate the BWAS patterns. Socioeconomic status (SES) -- not IQ or psychopathology -- showed the strongest associations with both resting-state functional connectivity (RSFC) and cortical thickness in the Adolescent Brain Cognitive Development (ABCD) Study. A principal exposome brain pattern, anchored to sensory and motor cortex, captured 34% of the variance across all BWAS maps. This exposome pattern was strongly correlated with the SES and IQ BWAS maps and non-BWAS maps of sleep (EEG), norepinephrine (PET), and stimulants (drug trial), but not cognitive activation maps (task fMRI). Adjusting for SES, reduced brain-IQ associations by 40%. Brain with IQ associations did not generalize, as they could no longer be detected in subsamples drawn from only higher SES backgrounds, while brain with SES associations remained strong in higher-IQ-only subsamples. These findings reveal SES as the principal axis of population-level brain variation, possibly stemming from the sleep deprivation and heightened stress associated with lower SES, since socioeconomics can only indirectly affect the brain.

neuroscience↗

bioRxiv2024

Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents

Understanding sex differences in the adolescent brain is crucial, as these differences are linked to neurological and psychiatric conditions that vary between males and females. Predicting sex from adolescent brain data may offer valuable insights into how these variations shape neurodevelopment. Recently, attention has shifted toward exploring socially-identified gender, distinct from sex assigned at birth, recognizing its additional explanatory power. This study evaluates whether resting-state functional connectivity (rsFC) or cortical thickness more effectively predicts sex and sex/gender alignment (the congruence between sex and gender) and investigates their interrelationship in preadolescents. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we employed machine learning to predict both sex (assigned at birth) and sex/gender alignment from rsFC and cortical thickness. rsFC predicted sex with significantly higher accuracy (86%) than cortical thickness (75%) and combining both did not improve the rsFC models accuracy. Brain regions most effective in predicting sex belonged to association (default mode, dorsal attention, and parietal memory) and visual (visual and medial visual) networks. The rsFC sex classifier trained on sex/gender aligned youth was significantly more effective in classifying unseen youth with sex/gender alignment than in classifying unseen youth with sex/gender unalignment. In females, the degree to which their brains rsFC matched a sex profile (female or male), was positively associated with the degree of sex/gender alignment. Lastly, neither rsFC nor cortical thickness predicted sex/gender alignment. These findings highlight rsFCs predictive power in capturing the relationship between sex and gender and the complexity of the interplay between sex, gender, and the brains functional connectivity and neuroanatomy.

neuroscience↗

bioRxiv2024

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N [~] 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a motor structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

neuroscience↗

bioRxiv2023

Framewise multi-echo distortion correction for superior functional MRI

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDICs framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI.

bioengineering↗

bioRxiv2023

Disuse-driven plasticity in the human thalamus and putamen

Motor adaptation in cortico-striato-thalamo-cortical loops has been studied mainly in animals using invasive electrophysiology. Here, we leverage functional neuroimaging in humans to study motor circuit plasticity in the human subcortex. We employed an experimental paradigm that combined two weeks of upper-extremity immobilization with daily resting-state and motor task fMRI before, during, and after the casting period. We previously showed that limb disuse leads to decreased functional connectivity (FC) of the contralateral somatomotor cortex (SM1) with the ipsilateral somatomotor cortex, increased FC with the cingulo-opercular network (CON) as well as the emergence of high amplitude, fMRI signal pulses localized in the contralateral SM1, supplementary motor area and the cerebellum. From our prior observations, it remains unclear whether the disuse plasticity affects the thalamus and striatum. We extended our analysis to include these subcortical regions and found that both exhibit strengthened cortical FC and spontaneous fMRI signal pulses induced by limb disuse. The dorsal posterior putamen and the central thalamus, mainly CM, VLP and VIM nuclei, showed disuse pulses and FC changes that lined up with fmri task activations from the Human connectome project motor system localizer, acquired before casting for each participant. Our findings provide a novel understanding of the role of the cortico-striato-thalamo-cortical loops in human motor plasticity and a potential link with the physiology of sleep regulation. Additionally, similarities with FC observation from Parkinson Disease (PD) questions a pathophysiological link with limb disuse.

neuroscience↗

bioRxiv2022

Motion Impact Score for Detecting Spurious Brain-Behavior Associations

Between-participant differences in head motion introduce systematic bias to resting state fMRI brain-wide association studies (BWAS) that is not completely removed by denoising algorithms. Researchers who study traits, or phenotypes associated with in-scanner head motion (e.g. psychiatric disorders) need to know if trait-functional connectivity (FC) effects are biased by residual motion artifact in order to avoid reporting false positive results. We devised an adaptable method, Split Half Analysis of Motion Associated Networks (SHAMAN), to assign a motion impact score to specific trait-FC effects. The SHAMAN approach distinguishes between motion artifact causing overestimation or underestimation of trait-FC effects. SHAMAN was > 95% specific at sample sizes of n = 100 and above. SHAMAN was powered to detect motion overestimation scores 80% of the time at sample sizes of n = 5,000 but could detect motion underestimation scores only 50% of the time at n = 5000, making it most useful for researchers seeking to avoid overestimating trait-FC effects in large BWAS. We computed motion impact scores for trait-FC effect with 45 demographic, biophysical, cognitive, and personality traits from n = 7,270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without motion censoring, 42% (19/45) of traits had significant (p < 0.05) motion overestimation scores and 38% (17/45) of traits had significant motion underestimation scores. Censoring at framewise displacement (FD) < 0.2 mm reduced the proportion of traits with significant motion overestimation scores from 42% to 2% (1/45) but did not decrease the number of traits with significant motion underestimation scores.

neuroscience↗

bioRxiv2022

A mind-body interface alternates with effector-specific regions in motor cortex

Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down precentral gyrus from foot to face representations1,2. The motor homunculus has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric functional zones3 and maps of complex actions4. Using our highest precision functional magnetic resonance imaging (fMRI) data and methods, we discovered that the classic homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function, alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, and to prefrontal, insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive action5 and physiological control6, arousal7, and processing of errors8 and pain9. This interdigitation of action control-linked and motor effector regions was independently verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI revealed potential cross-species analogues and developmental precursors of the inter-effector system. An extensive battery of motor and action fMRI tasks documented concentric somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-effector regions lacked movement specificity and co-activated during action planning (coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These results, together with prior work demonstrating stimulation-evoked complex actions4 and connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an integrative system for implementing whole-body action plans. Thus, two parallel systems intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot, hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative whole-organism coordination of goals, physiology, and body movement.

neuroscience↗

bioRxiv2021

Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks

The striatum is interconnected with the cerebral cortex via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate cortico-striatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited by the practice of averaging neuroimaging data across individuals. Here we utilized highly-sampled resting-state functional connectivity MRI for individually-specific precision functional mapping of cortico-striatal connections. We identified ten discrete, individual-specific subnetworks linking cortex--predominately frontal cortex--to striatum. These subnetworks included previously unknown striatal connections to the human language network. The discrete subnetworks formed a stepped rostral-caudal gradient progressing from nucleus accumbens to posterior putamen; this organization was strongest for projections from medial frontal cortex. The stepped gradient organization fit patterns of fronto-striatal connections better than a smooth, continuous gradient. Thus, precision subnetworks identify detailed, individual-specific stepped gradients of cortico-striatal connectivity that include human-specific language networks.

neuroscience↗

bioRxiv2021

Using synthetic MR images for field map-less distortion correction

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion combined with underlying differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) structural images makes the alignment of functional and anatomical images a challenge. Typically, separately acquired field map data are used to correct fMRI distortions and a flexible cost function insensitive to cross-modal differences in image contrast and intensity is used for aligning fMRI and anatomical images. The quality of alignment achieved with this approach can vary greatly and depends on the quality of field map data. In addition, many publicly available datasets lack field map data entirely. To address this issue, we developed Synth, a software package for distortion correction and cross-modal image registration that does not require separately acquired field map data. Synth combines information from T1w and T2w anatomical images to construct an idealized undistorted synthetic image that has similar contrast properties to fMRI data. The undistorted synthetic image then serves as an effective reference for individual-specific nonlinear unwarping to correct fMRI distortions. We demonstrate, in both pediatric (ABCD: Adolescent Brain Cognitive Development) and adult (MSC: Midnight Scan Club) data that Synth performs comparably well to other leading distortion correction approaches that utilize field map data, and often outperforms them. Field map-less distortion correction with Synth allows accurate and precise registration of fMRI data with missing or corrupted field map information.

neuroscience↗

bioRxiv2021

Precision Diffusion Imaging

Diffusion tensor imaging (DTI) aims to non-invasively characterize the anatomy and integrity of the brains white matter fibers. To establish individual-specific precision approaches for DTI, we defined its reliability and accuracy as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). DTI methods that allow for crossing fibers (BedpostX [BPX], Q-Ball Imaging [QBI]) estimated excess fibers when insufficient data was present and when the data did not match the model priors. To reduce such overfitting, we developed a novel crossing-fiber diffusion imaging method, Bayesian Multi-tensor Model-selection (BaMM), that is designed for high-quality repeated sampling data sets. BaMM was robust to overfitting, showing high reliability and the relatively best crossing-fiber accuracy with increasing amounts of diffusion data. Thus, the choice of diffusion imaging analysis method is important for the success of individual-specific diffusion imaging. Importantly, for potential clinical applications of individual-specific precision DTI, such as deep brain stimulation (DBS), other forms of neuromodulation or neurosurgical planning, the data quantities required to achieve DTI reliability are lower than for functional MRI measures.

neuroscience↗

bioRxiv2020

Parallel Hippocampal-Parietal Circuits for Self- and Goal-oriented Processing

The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. The human hippocampus has been thought of as being solely functionally connected to a set of neocortical regions known as the default mode network (DMN), which supports self-referential cognition. Using individual-specific precision functional mapping of resting state fMRI data, we found the anterior hippocampus (head and body) to be preferentially connected to the DMN as expected. The hippocampal tail, however, was strongly preferentially connected to the parietal memory network (PMN), which supports goal-oriented cognition and stimulus recognition. This resting state functional connectivity (RSFC) anterior-posterior dichotomy was well-matched by differences in task deactivations and anatomical segmentations of the hippocampus. Task deactivations were localized to the head and body of the hippocampus (DMN), relatively sparing the tail (PMN). Anterior and posterior hippocampal connectivity was network-specific even though the DMN and PMN are interdigitated in medial parietal cortex. The functional dichotomization of the hippocampus into anterior DMN-connected and posterior PMN-connected parcels suggests parallel, but distinct circuits between the hippocampus and medial parietal cortex for self vs. goal-oriented processing.

neuroscience↗

bioRxiv2020

Cingulo-Opercular Control Network Supports Disused Motor Circuits in Standby Mode

Whole-brain resting-state functional MRI (rs-fMRI) during two weeks of limb constraint revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula (1). Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions. SignificanceMany studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive control regions in the cingulo-opercular network (CON). Two complementary analyses, pulse censoring and pulse addition, demonstrated that increased functional connectivity between the CON and disused motor regions was driven by large, spontaneous pulses of activity in the CON and disused motor regions. These results point to a previously unknown role for the CON in supporting motor plasticity and reveal spontaneous activity pulses as a novel mechanism for reorganizing the brains functional connections.

neuroscience↗

bioRxiv2020

Towards Reproducible Brain-Wide Association Studies

Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25)1,2. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures4-6; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N{gap}2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.

neuroscience↗

bioRxiv2018

Correction of respiratory artifacts in MRI head motion estimates

Head motion represents one of the greatest technical obstacles for brain MRI. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, this estimation may be corrupted by factitious effects owing to main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and a comparison single-shot dataset from Oregon Health & Science University. We show unequivocally that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with degraded quality of functional MRI. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects. Subsequently, we demonstrate that utilizing this filter improves post-processing data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.

neuroscience↗