Biology subjects

Gulban, O. F.

Publications and source records attributed to Gulban, O. F..

At least 19 recordsLinked to original sources

bioRxiv2026

Peripheral Nerve Stimulation Optimized Pulses for EPI (POPE) allows high-resolution fMRI

PurposeRecent improvements in MRI gradient design and amplifiers, advanced MRI scanners are now routinely utilizing slew rates of several hundred T/m/s. However, full gradient performance cannot be exploited in high-resolution EPI due to peripheral nerve stimulation (PNS) limits. We aim to characterize and mitigate these PNS constraints using a simple sequence modification: PNS-optimized EPI gradient pulse shapes. MethodsPNS-Optimized Pulses for EPI (POPE): we selectively reduce the slew rate of gradient pulses at periods of high predicted PNS spikes, while leaving the rest of the waveform unchanged. PNS sensation was evaluated. ResultsPOPE allows 7%-35% faster imaging of EPI protocols resolutions of 1mm-0.3mm resolutions without exceeding predicted PNS. With such improvements, POPE allows robust 0.3 mm isotropic fMRI protocols that would have exceeded safety limits without it. ConclusionPOPE facilitates locally precise fMRI activation mapping on clinical 7T scanners at spatial resolution that were previously unattainable due to PNS limitations.

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bioRxiv2026

A probabilistic atlas of the human thalamic reticular nucleus derived from 7T MRI

The thalamic reticular nucleus (TRN) is a thin, inhibitory shell surrounding the thalamus. It regulates the thalamocortical information flow, and thereby plays a central role in attention, task switching, and the sleep-wake cycle. Despite its importance, the TRN remains poorly studied in the human brain. This is largely because its small size and deep anatomical location limit its visibility with conventional non-invasive neuroimaging techniques. Here, we assessed whether the human TRN can be reliably visualised and segmented in vivo using ultra-high field (UHF) magnetic resonance imaging (MRI) at 7 Tesla. High resolution (0.35 mm isotropic) partial-brain T2* and T1 scans were acquired from healthy individuals, followed by manual delineation of the TRN. These in vivo segmentations were compared with TRN estimates obtained from two high-quality postmortem datasets serving as an anatomical reference. In vivo segmentations of TRN volume and thickness closely matched measurements derived from the postmortem reference datasets, and quantitative comparisons showed high consistency in TRN shape and location across individuals while also capturing meaningful inter-individual variability. Using these segmentations, we constructed a publicly available probabilistic atlas of the human TRN. This atlas provides a new resource for incorporating TRN anatomy into functional, structural, and clinical neuroimaging studies. Our findings demonstrate that the human TRN can be robustly mapped in vivo at 7T and establish a foundation for future investigations into its structure and function.

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bioRxiv2026

Intracortical vessel density mapping at mesoscale reveals regionally specific angioarchitecture in the human brain

The metabolic demands of the human brain are met by a complex vascular architecture, yet our characterization of this network remains incomplete. While we have mapped the macroscopic vessels on the brains surface and the microscopic capillaries within small tissue samples, the mesoscopic scale consisting of the penetrating vessels that plunge through cortex remains an anatomical terra incognita. Mapping the interface between the macroscopic and microscopic scales is essential to understanding the critical vascular supply that sustains brain health. Here, we leveraged the BigBrain dataset and developed custom detection and tracing algorithms to reveal a whole-cortex record of the mesoscopic vascular network. We find that vascular density is not uniform across the cortex, but is a heterogeneous landscape that shows clear relationships to traditional areal boundaries. Our results constitute a reference for human mesoscopic angioarchitecture and demonstrates the power of repurposing high-resolution histological at-lases. Ultimately, this work lays the groundwork for validating recently developed in vivo MRI techniques for imaging the human cerebrovascular system at mesoscale.

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bioRxiv2025

In vivo reconstruction of Duvernoy's postmortem vasculature images

Non-invasive measurement of the human brains angioarchitecture is critical for understanding the basis of functional neuroimaging signals, diagnosing cerebrovascular diseases, and tracking neurodegeneration. Ultra-high-field magnetic resonance imaging (MRI) has achieved mesoscopic (< 0.5 mm) imaging of angioarchitecture, revealing fine vascular details that were previously inaccessible in vivo. However, current mesoscopic MRI methods for imaging angioarchitecture face two major limitations. First, acquisition times are prohibitively long, often exceeding 40 minutes, making integration into everyday clinical practice and research projects impractical. Second, even with data successfully acquired, conventional data visualization methods, such as 2D slice browsing and 3D vessel segmentation renders, are rudimentary and have limited effectiveness for navigating and interpreting the complex vascular network. In this paper, we present a fast whole-brain MRI protocol that provides robust images of the brains venous network at 0.35 mm resolution in under seven minutes. Additionally, we introduce novel data processing and visualization techniques that enable identification of specific vessel types and more informative navigation of the complex vascular network. We demonstrate that, with these advancements, we can reproduce, in vivo and without intravenous contrast application, the seminal postmortem vasculature images of Duvernoy and Vannson (1999). Furthermore, leveraging the ability for MRI to cover the entire brain, we achieve, for the first time, whole-brain intracortical mesoscopic vein maps in humans. Our acquisition and post-processing methods lay the groundwork for detailed examination of vascular organization across individuals, brain regions, and cortical layers. More generally, these methods make mesoscopic imaging of angioarchitecture viable for broad neuroscientific and clinical applications.

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bioRxiv2025

In the brain of the beholder: whole brain dynamics shape the perception during ambiguous motion

Visual perception is typically based on a one-to-one mapping between stimuli and conscious experiences. However, under bistable conditions, identical sensory inputs can elicit alternating perceptions, requiring the brain to resolve ambiguity. The mechanisms underlying transitions between distinct perceptual states and their sustained maintenance remain poorly understood. In this ultra-high-field (7T) fMRI study, we investigated the neural dynamics of perception using a bistable motion stimulus (ambiguous motion quartet) that evoked endogenous alternations between horizontal and vertical motion, compared to a control condition (physical motion quartet) with unambiguous sensory input. Consistent with previous findings, the human motion complex (hMT+) played a central role in processing both physical and ambiguous motion conditions. By dissociating neural activity during perceptual transitions from sustained perceptions, we found that hMT+ mostly interacts dynamically with area 46 in the frontal cortex and PF/PFm within the inferior parietal lobe during transitions and with subregions of the superior parietal lobe during sustained perceptions. Beyond local activity, computational modeling revealed an increase in hierarchical organization across cortical networks during the ambiguous condition. In particular, the same frontal and parietal regions exhibited ascension within the functional hierarchy, likely reflecting their specific role in coordinating computations for resolving ambiguity.

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bioRxiv2024

Multimodal laminar characterization of visual areas along the cortical hierarchy

Understanding the relationship between brain structure and function is a central goal in neuroscience. While post-mortem studies using microscopic techniques have provided detailed insights into the brains cytoarchitectonic and myeloarchitectonic patterns, linking these structural findings to functional outcomes remains challenging. Magnetic resonance imaging (MRI) has emerged as a powerful non-invasive tool for studying both structure and function, but discrepancies in spatial resolution between structural and functional imaging, especially in layer-fMRI, complicate the interpretation of functional results. In this study, we explore how visual cortical hierarchy relates to microscopic and mesoscopic laminar features. Focusing on visual areas that span progressive hierarchical levels, V1, V2, V3, and hMT+, we apply a multimodal approach combining post-mortem histology, post-mortem and in-vivo quantitative MRI (qMRI), and resting-state layer-fMRI. Using the open-access post-mortem AHEAD dataset, which integrates histological and qMRI contrasts from the same brain samples, we bridge microscopic observations with qMRI data. In parallel, we incorporate high-resolution [Formula] MRI and resting-state layer-fMRI from the same participant, allowing for a comparative analysis of laminar profiles across cortical depth. For computing laminar profiles, we developed an analysis pipeline that bridges histology images, mesoscopic qMRI, and layer-fMRI. Our findings highlight parvalbumin laminar profiles (reflecting interneuron parvalbumin density) as the most discriminative feature for differentiating brain areas. Additionally, we report laminar quantitative [Formula] profiles from post-mortem and in-vivo data, together with [Formula]-weighted resting-state layer-fMRI, all of which exhibit a similar overall shape across modalities. Using our methodological framework, a similar laminar characterization can be extended to study other brain regions. Generative models for layer fMRI will benefit from incorporating these new empirical microstructural (parvalbumin) and physical quantitative [Formula] data, leading to more area-specific and accurate models. HighlightsO_LIWe present a multimodal analysis of the laminar organization of four visual regions (V1, V2, V3, hMT+), characterizing progressive visual hierarchy levels in humans. This analysis spans from post-mortem microscopy and quantitative MRI (qMRI) to in-vivo qMRI and laminar fMRI during resting state. C_LIO_LIAmong the three microscopy contrasts, parvalbumin, a marker of interneuron density, emerges as the most distinctive regional feature. Notably, the parvalbumin laminar profiles vary across hierarchy levels, with hMT+ showing the greatest divergence compared to V1, V2, and V3. C_LIO_LIQuantitative [Formula] measurements, from both post-mortem and in-vivo data, reveal a clear increase towards the superficial cortical layers. These depth-dependent patterns closely mirror the laminar profiles observed in both task and resting-state fMRI. C_LIO_LISurprisingly, no substantial difference was observed in laminar [Formula] profiles between post-mortem and in-vivo data across the visual areas. C_LI

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bioRxiv2024

T1234: A distortion-matched structural scan solution to misregistration of high resolution fMRI data

PurposeHigh-resolution fMRI at 7T is challenged by suboptimal alignment quality between functional data and structural scans. This study aims to develop a rapid acquisition method that provides distortion-matched, artifact-mitigated structural reference data. MethodsWe introduce an efficient sequence protocol termed T1234, which offers adjustable distortions. This approach involves a T1-weighted 2-inversion 3D-EPI sequence with four spatial encoding directions optimized for high-resolution fMRI. A forward Bloch model was used for T1 quantification and protocol optimization. Twenty participants were scanned at 7T using both structural and functional protocols to evaluate the utility of T1234. ResultsResults from two protocols are presented. A fast distortion-free protocol reliably produced whole-brain segmentations at 0.8mm isotropic resolution within 3:00-3:40 minutes. It demonstrates robustness across sessions, participants, and three different 7T SIEMENS scanners. For a protocol with geometric distortions that matched functional data, T1234 facilitates layer-specific fMRI signal analysis with enhanced laminar precision. ConclusionThis structural mapping approach enables precise registration with fMRI data. T1234 has been successfully implemented, validated, and tested, and is now available to users at our center and at over 50 centers worldwide.

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bioRxiv2024

In the brain of the beholder: bi-stable motion reveals mesoscopic-scale feedback modulation in V1

Understanding the neural processes underlying conscious perception remains a central goal in neuroscience. Visual illusions, whether static or dynamic, provide an effective ecological paradigm for studying conscious perception, as they induce subjective experiences from constant visual inputs. While previous neuroimaging studies have dissociated perceptual interpretation of visual motion from sensory input within the motion-sensitive area (hMT+) in humans, less is known about the role of V1 and its relationship to hMT+ during a bistable perception. To address this, we conducted a layer-fMRI study at 7 T with human participants exposed to a bistable motion quartet stimulus. Despite a constant sensory input, the bistable motion quartet elicits switching horizontal and vertical apparent motion percepts likely due to lateral and feedback connections across low and high-level brain regions (feedback processing). As control, we used an "unambiguous" version of the motion quartet, hereafter referred to as "physical" motion stimulus, where horizontal and vertical motion is physically presented as visual stimulus in an alternated fashion (feedforward processing). With the advantage of a sub-millimeter resolution gained at ultra-high field (7 Tesla), we aimed to unveil the differential laminar modulation of V1 (low visual area) and hMT+ (high-visual area) during the physical and bistable condition. Our results indicate that: O_LIhMT+ functional activity correlates with conscious perception during both physical and ambiguous stimuli with similar strength. There is no evidence of differential laminar profiles in hMT+ between the two experimental conditions. C_LIO_LIBetween inducer squares, V1 shows a significantly reduced functional response to the ambiguous stimulus compared to the physical stimulus, as it primarily reflects feedback signals with diminished feedforward input. Distinct V1 laminar profiles differentiate the two experimental conditions. C_LIO_LIThe temporal dynamics of V1 and hMT+ become more similar during the ambiguous condition. C_LIO_LIV1 exhibits reduced specificity to horizontal and vertical motion perception during the ambiguous condition at the retinotopic locations corresponding to the perceived motion. C_LI Our findings demonstrate that during the ambiguous condition, there is a stronger temporal coupling between hMT+ and V1 due to feedback signals from hMT+ to V1. Such feedback to V1 might be contributing to the stabilization of the vivid perception of directed motion at the face of constant ambiguous stimulation.

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bioRxiv2024

Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation

PurposeHigh resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas. MethodsWe characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts. ResultsOur findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils. ConclusionThe proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: O_LIAchieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping. C_LIO_LISub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8. C_LIO_LISub-millimeter fMRI is achievable in lower brain areas, including the cerebellum. C_LI

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bioRxiv2024

Laminar CBV and BOLD response-characteristics over time and space in the human primary somatosensory cortex at 7T

Uncovering the cortical representation of the body has been at the core of human brain mapping for decades, with special attention given to the digits. In the last decade, advances in functional magnetic resonance imaging (fMRI) technologies have opened the possibility of noninvasively unraveling the 3rd dimension of digit representations in humans along cortical layers. In laminar fMRI it is common to combine the use of the highly sensitive blood oxygen level dependent (BOLD) contrast with cerebral blood volume sensitive measurements, like vascular space occupancy (VASO), that are more specific to the underlying neuronal populations. However, the spatial and temporal VASO response characteristics across cortical depth to passive stimulation of the digits are still unknown. Therefore, we characterized haemodynamic responses to vibrotactile stimulation of individual digit-tips across cortical depth at 0.75 mm in-plane spatial resolution using BOLD and VASO fMRI at 7T. We could identify digit-specific regions of interest (ROIs) in putative Brodmann area 3b, following the known anatomical organization. In the ROIs, the BOLD response increased towards the cortical surface due to the draining vein effect, while the VASO response was more shifted towards middle cortical layers, likely reflecting bottom-up input from the thalamus, as expected. Interestingly, we also found slightly negative BOLD and VASO responses for non-preferred digits in the ROIs, potentially indicating neuronal surround inhibition. Finally, we explored the temporal signal dynamics for BOLD and VASO as a function of distance from activation peaks resulting from stimulation of contralateral digits. With this analysis, we showed a triphasic response consisting of an initial peak and a subsequent negative deflection during stimulation, followed by a positive post-stimulus response in BOLD and to some extent in VASO. While similar responses were reported with invasive methods in animal models, here we demonstrate a potential neuronal excitation-inhibition mechanism in a center-surround architecture across layers in the human somatosensory cortex. Given that, unlike in animals, human experiments do not rely on anesthesia and can readily implement extensive behavioral testing, obtaining this effect in humans is an important step towards further uncovering the functional significance of the different aspects of the triphasic response.

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bioRxiv2024

VesselBoost: A Python Toolbox for Small Blood Vessel Segmentation in Human Magnetic Resonance Angiography Data

Magnetic resonance angiography (MRA) performed at ultra-high magnetic field provides a unique opportunity to study the arteries of the living human brain at the mesoscopic level. From this, we can gain new insights into the brains blood supply and vascular disease affecting small vessels. However, for quantitative characterization and precise representation of human angioarchitecture to, for example, inform blood-flow simulations, detailed segmentations of the smallest vessels are required. Given the success of deep learning-based methods in many segmentation tasks, we here explore their application to high-resolution MRA data, and address the difficulty of obtaining large data sets of correctly and comprehensively labelled data. We introduce VesselBoost, a vessel segmentation package, which utilizes deep learning and imperfect training labels for accurate vasculature segmentation. Combined with an innovative data augmentation technique, which leverages the resemblance of vascular structures, VesselBoost enables detailed vascular segmentations.

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bioRxiv2024

Characterisation of laminar and vascular spatiotemporal dynamics of CBV and BOLD signals using VASO and ME-GRE at 7T in humans

Interpretation of cortical laminar functional magnetic resonance imaging (fMRI) activity requires detailed knowledge of the spatiotemporal haemodynamic response across vascular compartments due to the well-known vascular biases (e.g. the draining veins). Further complications arise from the spatiotemporal hemodynamic response that differs depending on the duration of stimulation. This information is crucial for future studies using depth-dependent cerebral blood volume (CBV) measurements, which promise higher specificity for the cortical microvasculature than the blood oxygenation level dependent (BOLD) contrast. To date, direct information about CBV dynamics with respect to stimulus duration, cortical depth and vasculature is missing in humans. Therefore, we characterized the cortical depth-dependent CBV-haemodynamic responses across a wide set of stimulus durations with 0.9 mm isotropic spatial and 0.785 seconds effective temporal resolution in humans using slice-selective slabinversion vascular space occupancy (SS-SI VASO). Additionally, we investigated signal contributions from macrovascular compartments using fine-scale vascular information from multiecho gradient-echo (ME-GRE) data at 0.35 mm isotropic resolution. In total, this resulted in >7.5h of scanning per participant (n=5). We have three major findings: (I) While we could demonstrate that 1 second stimulation is viable using VASO, more than 12 seconds stimulation provides better CBV responses in terms of specificity to microvasculature, but durations beyond 24 seconds of stimulation may be wasteful for certain applications. (II) We observe that CBV responses show dilation patterns across the cortex. (III) While we found increasingly strong BOLD signal responses in vessel-dominated voxels with longer stimulation durations, we found increasingly strong CBV signal responses in vessel-dominated voxels only until 4 second stimulation durations. After 4 seconds, only the signal from non-vessel dominated voxels kept increasing. This might explain why CBV responses are more specific to the underlying neuronal activity for long stimulus durations.

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bioRxiv2023

Fast layer-fMRI VASO with short stimuli and event-related designs at 7T

Layers and columns are the dominant processing units in the human (neo)cortex at the meso-scopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical sur-face. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing com-plementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period (895 ms volume acqui-sition) and sub-millimetre resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials ([~]20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimu-lus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

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bioRxiv2022

Selective attention reduces responses to relevant sounds in human auditory cortex

Selective attention enables the preferential processing of relevant stimulus aspects. Invasive animal studies have shown that attending a sound feature rapidly modifies neuronal tuning throughout the auditory cortex. Human neuroimaging studies have reported enhanced auditory cortical responses with selective attention. To date, it remains unclear how the results obtained with functional magnetic resonance imaging (fMRI) in humans relate to the electrophysiological findings in animal models. Here we aim to close the gap between animal and human research by combining a selective attention task similar in design to those used in animal electrophysiology with high spatial resolution ultra-high field fMRI at 7 Tesla. Specifically, human participants perform a detection task, while the probability of target occurrence varies with sound frequency. Contrary to previous fMRI studies, we show that selective attention reduces responses to the attended frequencies in those neuronal populations preferring the attended frequency. Through population receptive field (pRF) mapping, we furthermore show that these response reductions are at least partially driven by frequency-induced pRF narrowing. The difference between our results to those of previous fMRI studies supports the notion that the influence of selective attention on auditory cortex is diverse and may depend on context, task, and auditory processing stage.

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bioRxiv2022

Acquisition and processing methods of whole-brain layer-fMRI VASO and BOLD: The Kenshu dataset.

Cortical depth-dependent functional magnetic resonance image (fMRI), also known as layer-fMRI, has the potential to capture directional neural information flow of brain computations within and across large-scale cortical brain networks. E.g., layer-fMRI can differentiate feedforward and feedback cortical input in hierarchically organized brain networks. Recent advancements in 3D-EPI sampling approaches and MR contrast generation strategies have allowed proof-of-principle studies showing that layer-fMRI can provide sufficient data quality for capturing laminar changes in functional connectivity. These studies have however not shown how reliable the signal is and how repeatable the respective results are. It is especially unclear whether whole-brain layer-fMRI functional connectivity protocols are widely applicable across common neuroscience-driven analysis approaches. Moreover, there are no established preprocessing fMRI methods that are optimized to work for whole-brain layer-fMRI datasets. In this work, we aimed to serve the field of layer-fMRI and build tools for future routine whole-brain layer-fMRI in application-based neuroscience research. We have developed publicly available sequences, acquisition protocols, and processing pipelines for whole-brain layer-fMRI. These protocols are validated across 60 hours of scanning in nine participants. Specifically, we identified and exploited methodological advancements for maximizing tSNR efficiency and test-retest reliability. We are sharing an extensive multi-modal whole-brain layer-fMRI dataset (20 scan hours of movie-watching in a single participant) for the purpose of benchmarking future method developments: The Kenshu dataset. With this dataset, we are also exemplifying the usefulness of whole brain layer-fMRI for commonly applied analysis approaches in modern cognitive neuroscience fMRI studies. This includes connectivity analyses, representational similarity matrix estimations, general linear model analyses, principal component analysis clustering, etc. We believe that this work paves the road for future routine measurements of directional functional connectivity across the entire brain. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/504502v1_ufig1.gif" ALT="Figure 1"> View larger version (89K): org.highwire.dtl.DTLVardef@1c6579forg.highwire.dtl.DTLVardef@a2bbecorg.highwire.dtl.DTLVardef@1dfa41aorg.highwire.dtl.DTLVardef@18ee67f_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2022

Laminar VASO fMRI in focal hand dystonia patients

Focal Hand Dystonia (FHD) is a disabling movement disorder characterized by involuntary movements, cramps and spasms. It is associated with pathological neural microcircuits in the cortical somatosensory system. While invasive preclinical modalities allow researchers to probe specific neural microcircuits of cortical layers and columns, conventional functional magnetic resonance imaging (fMRI) cannot resolve such small neural computational units. In this study, we take advantage of recent developments in ultra-high-field MRI hardware and MR-sequences to capture altered digit representations and laminar processing in FHD patients. We aim to characterize the capability and challenges of layer-specific imaging and analysis tools in resolving laminar and columnar structures in clinical research setups. We scanned N=4 affected and N=5 unaffected hemispheres at 7T and found consistent results of altered neural microcircuitry in FHD patients: a) In affected hemispheres of FHD patients, we found a breakdown of ordered finger representation in the primary somatosensory cortex, as suggested from previous low-resolution fMRI. b) In affected primary motor cortices of FHD patients, we furthermore found increased fMRI activity in superficial cortico-cortical neural input layers (II/III), compared to relatively weaker activity in the cortico-spinal output layers (Vb/VI). Overall, we show that layer-fMRI acquisition and analysis tools are applicable to address clinically-driven neuroscience research questions about altered computational mechanisms at the spatial scales that were previously only accessible in animal models. We believe that this study paves the way for easier translation of preclinical work into clinical research in focal hand dystonia and beyond.

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bioRxiv2022

Imaging the columnar functional organization of human area MT+ to axis-of-motion stimuli using VASO at 7 Tesla

Cortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (<1 mm) in the homologous brain area (hMT+, V5) in living humans by using ultra-high field functional magnetic resonance imaging (fMRI). Despite the reproducibility of the selective response to axis-of-motion stimuli, clear quantitative evidence for the columnar organization of hMT+ is still lacking. Using cerebral blood volume (CBV)-sensitive fMRI at 7 Tesla with submillimeter resolution and high spatial specificity to microvasculature, we investigate the columnar functional organization of hMT+ in 5 participants perceiving axis-of-motion stimuli for both blood oxygenation level dependent (BOLD) and vascular space occupancy (VASO) contrast mechanisms provided by the used Slab-Selective Slice Inversion (SS-SI)-VASO sequence. With the development of a new searchlight algorithm for column detection, we provide the first quantitative columnarity map that characterizes the entire 3D hMT+ volume. Using voxel-wise measures of sensitivity and specificity, we demonstrate the advantage of using CBV-sensitive fMRI to detect mesoscopic cortical features by revealing higher specificity of axis-of-motion cortical columns for VASO as compared to BOLD contrast. These voxel-wise metrics also provide further insights on how to mitigate the highly debated draining veins effect. We conclude that using CBV-VASO fMRI together with voxel-wise measurements of sensitivity, specificity and columnarity offers a promising avenue to quantify the mesoscopic organization of hMT+ with respect to axis-of-motion stimuli. Furthermore, our approach and methodological developments are generalizable and applicable to other human brain areas where similar mesoscopic research questions are addressed.

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bioRxiv2021

The influence of non-neural factors on BOLD signal magnitude

To what extent is the size of the blood-oxygen-level-dependent (BOLD) response influenced by factors other than neural activity? In a re-analysis of three neuroimaging datasets (male and female human participants), we find large systematic inhomogeneities in the BOLD response magnitude in primary visual cortex (V1): stimulus-evoked BOLD responses, expressed in units of percent signal change, are up to 50% larger along the representation of the horizontal meridian than the vertical meridian. To assess whether this surprising effect can be interpreted as differences in local neural activity, we quantified several factors that potentially contribute to the size of the BOLD response. We find relationships between BOLD response magnitude and cortical thickness, curvature, depth and macrovasculature. These relationships are consistently found across subjects and datasets and suggest that variation in BOLD response magnitudes across cortical locations reflects, in part, differences in anatomy and vascularization. To compensate for these factors, we implement a regression-based correction method and show that after correction, BOLD responses become more homogeneous across V1. The correction reduces the horizontal/vertical difference by about half, indicating that some of the difference is likely not due to neural activity differences. We conclude that interpretation of variation in BOLD response magnitude across cortical locations should consider the influence of the potential confounding factors of thickness, curvature, depth and vascularization. Significance statementThe magnitude of the BOLD signal is often used as a surrogate of neural activity, but the exact factors that contribute to its strength have not been studied on a voxel-wise level. Here, we examined several anatomical and measurement-related factors to assess their relationship with BOLD signal magnitude. We find that BOLD magnitude correlates with cortical anatomy, depth and macrovasculature. To remove the contribution of these factors, we propose a simple, data-driven correction method that can be used in any functional magnetic resonance imaging (fMRI) experiment. After accounting for the confounding factors, BOLD magnitude becomes more spatially homogenous. Our correction method improves the ability to make more accurate inferences about local neural activity from fMRI data.

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