Biology subjects

Farahani, A.

Publications and source records attributed to Farahani, A..

12 recordsLinked to original sources

bioRxiv2026

Cerebral vasculature shapes the spatial patterning of brain metastases

Primary cancer cells that originate in diverse tissues in the body can spread to the brain through various physiological pathways and form metastatic tumors. The spatial patterning of brain metastases is highly stereotyped across individuals, but the physiological factors that confer regional vulnerability to tumor colonization are poorly understood. Here we map the brain metastases associated with primary breast cancer, lung cancer, and malignant melanoma to the multiscale organization of the brain. We analyze structural magnetic resonance imaging (MRI) data from more than 2, 300 cancer patients with approximately 10, 000 brain metastases to estimate metastatic frequency maps. We then examine whether transcriptional (microarray profiling), functional (functional MRI), and vascular (arterial spin labeling) features can predict the spatial pattern of each brain metastasis type. Our analyses highlight vascular anatomy as an integral determinant of metastatic patterning, particularly in breast and lung cancers. We find arterial border-zones as sites of elevated vulnerability to metastatic invasion. These areas, characterized by slow flow and small-caliber vessels, create a hemodynamic environment that favors the arrest and extravasation of circulating tumor cells. Together, these results provide quantitative support for the long-standing hypothesis that vascular architecture and its biomechanical properties constrain metastatic seeding in the brain. Identifying vascular topology as a key determinant of metastatic patterning suggests that systemic vascular and metabolic factors may contribute to metastatic risk.

neuroscience↗

bioRxiv2026

The blueprint of human functional architecture shifts from cognition to anatomy during perturbations of consciousness

Consciousness and cognition arise from the ongoing interactions between brain regions. Synchronous fluctuations of fMRI signals may indicate that two brain regions perform similar cognitive functions, but neural interactions are also constrained by anatomical connectivity and regions molecular, cytoarchitectonic, and metabolic profiles. Here we disentangle the respective contributions of ongoing cognition and multimodal neurobiological constraints in shaping functional connectivity. We jointly contextualise haemodynamic FC against eight distinct multimodal representations of the human connectome: (i) structural connectivity from diffusion tractography; (ii) spatial embedding; (iii) similarity of transcriptional profiles from gene expression; (iv) similarity of receptor profiles from Positron Emission Tomography; (v) laminar profile similarity from histology; (vi) correlated electrophysiological activity from magnetoencephalography; (vii) correlated metabolic activity from PET glucose uptake; (viii) coordinated activation across 123 cognitive operations from the NeuroSynth meta-analytic engine. We demonstrate that cognitive co-activation is the dominant predictor of inter-regional fMRI synchrony in the awake human brain, even when quantified using intracranial electrical stimulation. Crucially, this predominance of cognitive co-activation for shaping functional connectivity is systematically obliterated across five datasets of pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anaesthesia with sevoflurane, propofol, or ketamine) when cognition is disconnected from the environment or altogether abolished. Altogether, we show that multimodal predictors of functional architecture shift away from cognitive co-activation and toward anatomicalmolecular constraints during pharmacological and pathological perturbations of consciousness.

neuroscience↗

bioRxiv2026

Structure-function coupling in the human brainstem

The nuclei of the brainstem fundamentally modulate neuronal activity throughout the central nervous system. Yet connectome reconstructions typically do not include the brainstem because it is notoriously difficult to image. As a result, the influence of the brainstem on structure-function coupling in the brain is unknown. Here we use high-resolution 7 Tesla magnetic resonance imaging (MRI) to reconstruct structural and functional brain connectomes encompassing cortex and 58 brainstem nuclei spanning the midbrain, pons, and medulla. We identify structural connectional profiles of individual brainstem nuclei to the cortex and find that they align with a spectrum of functions, spanning sensory and motor processing to higher-order cognition. Structural and functional connectivity in brainstem-augmented connectomes are positively correlated, and pairs of regions with direct anatomical projections display greater functional connectivity than pairs without. Structure-function coupling is heterogeneous across brainstem nuclei, with greatest coupling in both modulatory and relay nuclei. Collectively, this work presents an initial step towards understanding how the brainstem shapes structure-function relationships in the brain.

neuroscience↗

bioRxiv2026

Spatial organization of AQP4 channels in the human brain: links with perfusion, edema, and disease vulnerability

Aquaporin-4 (AQP4) water channels support the glymphatic system, a brain-wide pathway that clears cerebral waste products. Despite its importance, the whole-brain organization of this system in humans remains underexplored. Here we use AQP4 gene expression as a molecular anchor to reconstruct a whole-brain glymphatic-related topography and link it to vascular physiology, edema, and neurode-generative vulnerability. We find that AQP4 expression is highly organized across the brain, peaking in subcortical, ventral, and periventricular territories, consistent with a clearance axis near cerebrospinal fluid reservoirs and perivascular interfaces. Linking AQP4 expression to vascular organization, we find that AQP4-enriched regions show lower normative blood perfusion and lower vein density, suggesting that this axis is not simply explained by vascular supply or large-vessel anatomy. Turning to neurodegeneration, we find that atrophy patterns across multiple neurodegenerative diseases co-localize with AQP4 expression--most strongly for tau and TDP-43 proteinopathies--and high-atrophy regions lie close to AQP4 hotspots in both anatomical space and structural connectome space. Furthermore, incorporating normative PET markers of neuroinflammation typically strengthens the spatial alignment between AQP4 expression and disease atrophy, suggesting that inflammatory tone and glymphatic-related architecture jointly shape vulnerability. Finally, we show that peritumoral edema is most frequent in AQP4-enriched regions and is further shaped by regional inflammatory tone. Collectively, this work highlights a whole-brain glymphatic organization that relates to diverse aspects of brain physiology and vulnerability.

neuroscience↗

bioRxiv2025

Joint multi-omics profiling of brain and body health in aging

The human brain and peripheral systems undergo coordinated changes throughout the lifespan, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to peripheral biomarkers of bodily health including body mass index, blood pressure, and blood biochemistry results. We use partial least squares analysis to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and arterial spin labeling MRI), demographic, and peripheral physiological markers in two large-scale deeply phenotyped datasets: the Human Connectome Project-Aging and UK Biobank. This data-driven pattern learning approach identifies two principal axes of brain-body associations in both biological sex groups. The first axis is driven by the dominant contribution of age. Across multiple brain measures, aging is associated with loss of brain structural integrity and cerebral vascular dysfunction. The second axis is driven by metabolic features, characterized by low high-density lipoprotein cholesterol, elevated body mass index, blood pressure, glycosylated hemoglobin, insulin, glucose, and alanine aminotransferase, and reduced cerebral blood perfusion. Finally, we show that deviations from a healthy metabolic profile are linked to cognitive deficits, particularly in females. Our study contributes to development of comprehensive translatable biomarkers for brain health assessment, and highlights the importance of metabolic health as a determinant of brain health.

neuroscience↗

bioRxiv2025

netneurotools: a trainee-oriented approach to network neuroscience

Brain imaging is an increasingly inter-disciplinary field, encompassing multiple data types and multiple analytic traditions. Projects typically involve many moving parts, such as building customized preprocessing pipelines, transforming between data formats, preparing datasets for analysis, and ultimately displaying results. The field is conventionally built on highly specialized software packages that solve these individual challenges well, but are not necessarily designed to be interoperable. Trainees new to the field are therefore often left to come up with isolated heuristics and workarounds to complete a project. Here we present a way to navigate the increasingly complex informatics ecosystem of brain imaging. netneurotools is our labs internal Python toolkit that has been continuously developed and maintained by the labs trainees. The philosophy of the toolkit is that it should be the Swiss army knife of the lab: functions and routines that we often use but that are not part of any established pipeline or package. Since its inception, the toolkit has been open and welcomes contribution from neuroscientists across the globe. netneurotools presents a necessary counterweight to out-of-the-box software packages and highlights the importance of smaller, ad hoc functions for implementing projects. By opening a window into the inner workings of a lab, netneurotools also presents an opportunity to begin a new type of discourse among groups and establish tangible links within the community.

neuroscience↗

bioRxiv2025

A network of face patches in human prefrontal cortex for social processing of faces

The human cerebral cortex contains localized regions for processing faces. These regions or patches, which are classically found in the occipito-temporal cortex, encode visual properties of faces. Using naturalistic movie-watching fMRI data from 176 human subjects and multivariate functional connectivity analysis, here we comprehensively characterize a novel network of four frontal face patches (FFPs) arranged dorsoventrally in the lateral prefrontal cortex. FFPs are strongly coupled with a face-selective region in the middle superior temporal sulcus, appear to be primarily involved in processing high-level social aspects of faces during movie-watching, and show partial correlations of activity with distinct cognitive networks. Activations in FFPs are correlated with the performance of subjects in a social cognition task. We further identify two groups of subjects who showed a remarkable difference in the topographical organization of FFPs. The discovery of FFPs provides new insights into the understanding of social processing in the brain.

neuroscience↗

bioRxiv2025

Cerebral blood perfusion across biological systems and the human lifespan

Blood perfusion delivers oxygen and nutrients to all cells, making it a fundamental feature of brain organization. How cerebral blood perfusion maps onto micro-, meso- and macro-scale brain structure and function is therefore a key question in neuroscience. Here we analyze pseudo-continuous arterial spin labeling (ASL) data from 1 305 healthy individuals in the HCP Lifespan studies (5-100 years) to reconstruct a high-resolution normative cerebral blood perfusion map. At the cellular and molecular level, cerebral blood perfusion co-localizes with granular layer IV, biological pathways for maintenance of cellular relaxation potential and mitochondrial organization, and with neurotransmitter and neuropeptide receptors involved in vasomodulation. At the regional level, blood perfusion aligns with cortical arealization and is greatest in regions with high metabolic demand and resting-state functional hubs. Looking across individuals, blood perfusion is dynamic throughout the lifespan, follows microarchitectural changes in development, and maps onto individual differences in physiological changes in aging. In addition, we find that cortical atrophy in multiple neurodegenerative diseases (late-onset Alzheimers disease, TDP-43C, and dementia with Lewy bodies) is most pronounced in regions with lower perfusion, highlighting the utility of perfusion topography as an indicator of transdiagnostic vulnerability. Finally, we show that ASL-derived perfusion can be used to delineate arterial territories in a data-driven manner, providing insights into how the vascular system is linked to human brain function. Collectively, this work highlights how cerebral blood perfusion is central to, and interlinked with, multiple structural and functional systems in the brain.

neuroscience↗

bioRxiv2024

Mapping neuropeptide sigaling in the human brain

Neuropeptides are functionally diverse signaling molecules in the brain, regulating a wide range of basal bodily and cognitive processes. Despite their importance, the distribution and function of neu-ropeptides in the human brain remains underexplored. Here we comprehensively map the organization of human whole-brain neuropeptide receptors across multiple levels of description; from molecular and cellular embedding to mesoscale connectivity and macroscale cognitive specialization. Using gene transcription as a proxy, we reconstruct a topographic cortical and subcortical atlas of neuropeptide receptors for 38 neuropeptide receptors, across 14 different neuropeptide families. We find that most neuropeptide receptors are highly expressed either in cortex or subcortex, delineating an anatomical cortical-subcortical gradient. Neuropeptides preferentially co-localize with metabotropic neurotrans-mitters, suggesting a system-wide correspondence between slow-acting molecular signaling mechanisms. Mapping neuropeptide receptors and their cognate ligands onto white-matter connectomes, we demonstrate that specific neuropeptides families shape electrophysiological and haemodynamic interregional connectivity. To investigate the behavioural consequences of distributed neuropeptide systems, we apply meta-analytic decoding to neuropeptide maps and show a gradient of functions, from sensory-cognitive to reward and bodily functions. Finally, evolutionary analysis indicates extended positive selection for neuropeptides in early mammals, suggesting that refinement of neuropeptides coincides with the emergence of neocortex and higher cognitive function. Collectively, these results show that the neuropeptide receptors are highly organized across the human brain and closely intertwined with multiple features of brain structure and function.

neuroscience↗

bioRxiv2024

Local lateral connectivity is sufficient for replicating cortex-like topographical organization in deep neural networks

Across the primate cortex, neurons that perform similar functions tend to be spatially grouped together. This biological principle extends to many other species as well, reflecting a common way of organizing sensory processing across diverse forms of life. In the visual cortex, this biological principle manifests itself as a modular organization of neuronal clusters, each tuned to a specific visual property. The tendency toward short connections is widely believed to explain the existence of such an organization in the brains of many animals. However, the neural mechanisms underlying this phenomenon remain unclear. Here, we use artificial deep neural network models to demonstrate that a topographical organization akin to that in the primary, intermediate, and high-level human visual cortex emerges when units in these models are locally laterally connected and their weight parameters are tuned by top-down credit assignment. The emergence of modular organization without explicit topography-inducing learning rules or objective functions challenges their necessity and suggests that local lateral connectivity alone may suffice for the formation of topographic organization across the cortex. Furthermore, the incorporation of lateral connections in deep convolutional networks enhances their robustness to subtle alterations in visual inputs, such as those designed to deceive the model (i.e. adversarial examples), indicating an additional role for these connections in learning robust representations.

neuroscience↗

bioRxiv2024

Network Spreading and Local Biological Vulnerability in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that predominantly targets the motor system. Spread of pathology is thought to be driven by both local vulnerability and network architecture. Namely, molecular and cellular features may confer vulnerability to specific neuronal populations, while synaptic contacts may also increase exposure to pathology in connected neuronal populations. However, these principles are typically studied in isolation and it remains unknown how local vulnerability and network spreading interact to shape cortical atrophy. Here we investigate how network structure and local biological features jointly shape the spatial patterning of atrophy in ALS. We analyze the Canadian ALS Neuroimaging Consortium (CALSNIC) dataset and estimate cortical atrophy using deformation-based morphometry (DBM). We find that structural connectivity closely aligns with the course of atrophy. Atrophy is also more likely to occur in regions that share similar transcriptomic, neurotransmitter receptor and metabolic profiles. We identify disease epicenters in motor cortex. Epicenter probability maps show transcriptomic enrichment for biological pathways involved in mitochondrial function as well as support cells, including endothelial cells and pericytes. Finally, individual differences in epicenter location correspond to individual differences in clinical and cognitive symptoms, and differentiate patient subtypes.

neuroscience↗

bioRxiv2022

Functional architecture of cerebral cortex during naturalistic movie-watching

Characterizing the functional organization of cerebral cortex is a fundamental step in understanding how different kinds of information are processed in the brain. Neuroimaging studies over the past decades have uncovered the function of many cortical areas in response to selected stimulus categories. However, it is still unclear how cortical areas are organized during naturalistic visual and auditory stimulation. Here we used high-resolution functional MRI data from 176 human subjects to map the macro-architecture of the entire cerebral cortex based on responses to a 60-minute audiovisual movie stimulus. A data-driven clustering approach revealed a map of 24 functional areas/networks, each related to a specific aspect of sensory or cognitive processing. The map included three distinct executive control (domain-general) networks which showed a strong push-pull interaction with domain-specific regions in visual, auditory, and language cortex. The cortical parcellation scheme presented here provides a comprehensive and unified map of functionally defined areas, which could replace a large set of functional localizer maps.

neuroscience↗