Biology subjects

Huber, L.

Publications and source records attributed to Huber, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Action observation reveals a network with divergent temporal and parietal lobe engagement in dogs compared to humans

Action observation is a fundamental pillar of social cognition. Neuroimaging research has revealed a human and primate action observation network (AON) encompassing fronto-temporo-parietal areas with links to a species imitation tendencies and relative lobe expansion. Dogs (Canis familiaris) have good action perception and imitation skills and a less expanded parietal than temporal lobe, but their AON remains unexplored. We conducted a functional MRI study with 28 dogs and 40 humans and found functionally analogous involvement of somatosensory and temporal brain areas of both species AONs and responses to transitive and intransitive action observation in line with their imitative skills. However, activation and task-based functional connectivity measures suggested significantly less parietal lobe involvement in dogs than in humans. These findings advance our understanding of the neural bases of action understanding and the convergent evolution of social cognition, with analogies and differences resulting from similar social environments and divergent brain expansion, respectively.

neuroscience↗

bioRxiv2023

Interplay between PLEKHG3-regulated actin dynamics and lysosomal trafficking in cell motility

Lysosomes are dynamic organelles regulating metabolic signaling by recruiting cytosolic molecules to protein platforms on their limiting membrane. We used proximity labeling to define interactors and vicinal proteins of LAMTOR3, a component of the Ragulator scaffold that controls mTORC1 signaling and lysosome positioning. The screen has yielded several previously unappreciated interactors, including an actin remodeling network. Here, we characterize the RhoGEF PLEKHG3 as a LAMTOR3 vicinal protein colocalizing with peripheral lysosomes and cortical F-actin at focal adhesion sites. Forced peripheral dispersion of lysosomes drives PLEKHG3 accumulation at focal adhesions and decreases protrusive activity in both wild-type and PLEKHG3-deficient cells. Thus, lysosome positioning governs both PLEKHG3 localization and protrusive activity, yet the protrusion changes can occur independently of PLEKHG3.

cell biology↗

bioRxiv2022

A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma

SUMMARY PARAGRAPHDisease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1-3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4, 5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T>C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6, 7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.

cancer biology↗

bioRxiv2022

Structural basis for mTORC1-dependent regulation of the lysosomal and autophagic transcription factor TFEB

The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1) is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino-acid-mediated activation of the RagC GAP FLCN. TFEB lacks the TOR signaling (TOS) motif responsible for the recruitment of other mTORC1 substrates. We used cryo-electron microscopy (cryo-EM) to determine the structure of TFEB as presented to mTORC1 for phosphorylation. Two full Rag-Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag-Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag-Ragulator complex (non-canonical) docks onto the first via a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB in a RagCGDP-dependent aspartate clamp in the cleft between the Rag G domains. Mutation of the clamp drives TFEB constitutively into the nucleus whilst having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. This structure presents the phosphorylatable Ser residues of TFEB to the mTORC1 active site in a suitable geometry for their phosphorylation. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.

cell biology↗

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

neuroscience↗

bioRxiv2022

Cerebral blood volume sensitive layer-fMRI in the human auditory cortex at 7 Tesla: Challenges and capabilities

The development of ultra high field (UHF) fMRI signal readout strategies and contrasts has led to the possibility of imaging the human brain in vivo and non-invasively at increasingly higher spatial resolutions of cortical layers and columns. One emergent layer-fMRI acquisition method with increasing popularity is the cerebral blood volume (CBV) sensitive sequence named vascular space occupancy (VASO). This approach has been shown to be mostly sensitive to locally-specific changes of laminar microvasculature, without unwanted biases of trans-laminar draining veins. Until now, however, VASO has not been applied in the technically challenging cortical area of the primary auditory cortex. Here, we developed a VASO imaging protocol for auditory neuroscientific applications. We describe the main challenges we encountered and the solutions we have adopted to mitigate them. With our optimized protocol, we investigate laminar responses to sounds. Finally, as proof of concept for future investigations, we map the topographic representation of frequency preference (tonotopy) in the auditory cortex. HighlightsO_LILayer fMRI VASO in the auditory cortex is challenging due to its physiology C_LIO_LIAfter protocol optimization we show the applicability of VASO to the auditory cortex C_LIO_LITopographic maps obtained with VASO respect the large-scale tonotopic organization that has previously been shown with BOLD fMRI data. C_LI

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Evaluating the capabilities and challenges of layer-fMRI VASO at 3T

Sub-millimeter functional imaging has the potential to capture cortical layer-specific functional information flow within and across brain systems. Recent sequence advancements of fMRI signal readout and contrast generations resulted in wide adaptation of layer-fMRI protocols across the global ultra-high-field (UHF) neuroimaging community. However, most layer-fMRI applications are confined to one of {approx}100 privileged UHF imaging centers, and sequence contrasts with unwanted sensitivity to large draining veins. In this work, we propose the application of vein-signal free vascular space occupancy (VASO) layerfMRI sequences at widely accessible 3T scanners. Specifically, we implement, characterize, and apply a cerebral blood volume (CBV)-sensitive VASO fMRI at a 3T scanner setup, as it is typically used in the majority of cognitive neuroscience and clinical neuroscience fMRI studies. We find that the longer [Formula], and stronger relative T1 contrast at 3T can account for some of the lower z-magnetization in the inversion-recovery VASO sequence compared to 7T and 9.4T. In the main series of experiments (N=16), we test the utility of this setup for motor tasks and find that-while being limited by thermal noise-3T layer-fMRI VASO is feasible within conventional scan durations. In a series of auxiliary studies, we furthermore explore the generalizability of the developed layer-fMRI protocols for a larger range of study designs including: visual stimulation, whole brain movie watching paradigms, and cognitive tasks with weaker effect sizes. We hope that the developed imaging protocols will help to increase accessibility of vein-signal free layer-fMRI imaging tools to a wider community of neuroimaging centers. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/501554v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@1b2c6b5org.highwire.dtl.DTLVardef@139b13org.highwire.dtl.DTLVardef@129ff82org.highwire.dtl.DTLVardef@45e9d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Unwilling or Unable? Using 3D tracking to evaluate dogs' reactions to differing human intentions.

The extent to which dogs (Canis familiaris) as a domesticated species understand human intentions is still a matter of debate. The unwilling-unable paradigm has been developed to examine whether nonhuman animals are sensitive to intentions underlying human actions. In this paradigm, subjects tended to show more patience toward a human that appears willing but unable to transfer food to them compared to an unwilling (teasing) human. In the present study, we conducted the unwilling-unable paradigm with dogs using a detailed behavioural analysis based on machine-learning driven 3D tracking. Throughout two preregistered experiments, we found evidence, in line with our prediction, that dogs reacted more impatiently to actions signalling unwillingness to transfer food rather than inability. These differences were consistent through two different samples of pet dogs (total N=96) and they were evident also in the machine-learning generated 3D tracking data. Our results, therefore, provide robust evidence that dogs distinguish between similar actions (leading to the same outcome) associated with different intentions. However, their reactions did not lead to any measurable preference for one experimenter over the other in a subsequent transfer phase. We discuss different cognitive mechanisms that might underlie dogs performance in this paradigm.

animal behavior and cognition↗

bioRxiv2022

Validation of a new coil array tailored for dog functional magnetic resonance imaging (fMRI) studies

Comparative neuroimaging allows for the identification of similarities and differences between species. It provides an important and promising avenue, to answer questions about the evolutionary origins of the brains organization, in terms of both structure and function. Dog fMRI has recently become one particularly promising and increasingly used approach to study brain function and coevolution. In dog neuroimaging, image acquisition has so far been mostly performed with coils originally developed for use in human MRI. Since such coils have been tailored to human anatomy, their sensitivity and data quality is likely not optimal for dog MRI. Therefore, we developed a multi-channel receive coil (K9 coil) tailored for high-resolution functional imaging in canines, optimized for dog cranial anatomy. In this paper we report structural (n = 9) as well as functional imaging data (resting-state, n = 6; simple visual paradigm, n = 9) collected with the K9 coil in comparison to reference data collected with a human knee coil. Our results show that the K9 coil significantly outperforms the human knee coil, improving the signal-to-noise ratio across the imaging modalities. We noted increases of roughly 45% signal-to-noise in the structural and functional domain. In terms of translation to functional fMRI data collected in a visual flickering checkerboard paradigm, group-level analyses show that the K9 coil performs better than the knee coil as well. These findings demonstrate how hardware improvements may be instrumental in driving data quality, and thus, quality of imaging results, for dog-human comparative neuroimaging. Significance StatementComparative neuroimaging is a powerful avenue to discover evolutionary mechanisms at the brain level. However, data quality is a major constraint in non-human functional magnetic resonance imaging. We describe a novel canine head coil for magnetic resonance imaging, designed specifically for dog cranial anatomy. Data quality performance and improvements over previously used human knee coils are described quantitatively. In brief, the canine coil improved signal quality substantially across both structural and functional imaging domains, with strongest improvements noted on the cortical surface.

neuroscience↗

bioRxiv2021

Similarities and differences of face and body perception in the dog (Canis familiaris) and human brain

Comparing the neural correlates of socio-cognitive skills across species provides insights into the evolution of the social brain and has revealed face- and body-sensitive regions in the primate temporal lobe. Although from a different lineage, dogs share convergent visuo-cognitive skills with humans and a temporal lobe which evolved independently in carnivores. We investigated the neural correlates of face and body perception in dogs (N = 15) and humans (N = 40) using functional MRI. Combining univariate and multivariate analysis approaches, we found functionally analogous occipito-temporal regions involved in the perception of animate entities and bodies in both species, while only humans had regions specialized for face perception. Though unpredicted, we also observed neural representations of faces compared to inanimate objects, and dog compared to human bodies in dog olfactory regions. These findings shed light on the evolutionary foundations of human and dog social cognition and the predominant role of the temporal lobe.

neuroscience↗

bioRxiv2020

Sub-millimetre resolution laminar fMRI using Arterial Spin Labelling in humans at 7T

Laminar fMRI at ultra-high magnetic field strength is typically carried out using the Blood Oxygenation Level-Dependent (BOLD) contrast. Despite its unrivalled sensitivity to detecting activation, the BOLD contrast is limited in its spatial specificity due to signals stemming from intra-cortical ascending and pial veins. Alternatively, regional changes in perfusion (i.e., cerebral blood flow through tissue) are colocalised to neuronal activation, which can be non-invasively measured using arterial spin labelling (ASL) MRI. In addition, ASL provides a quantitative marker of neuronal activation in terms of perfusion signal, which is simultaneously acquired along with the BOLD signal. However, ASL for laminar imaging is challenging due to the lower SNR of the perfusion signal and higher RF power deposition i.e., specific absorption rate (SAR) of ASL sequences. In the present study, we present for the first time in humans, isotropic sub-millimetre spatial resolution functional perfusion images using Flow-sensitive Alternating Inversion Recovery (FAIR) ASL with a 3D-EPI readout at 7T. We show that robust statistical activation maps can be obtained with perfusion-weighting in a single session. We observed the characteristic BOLD amplitude increase towards the superficial laminae, and, in apparent discrepancy, the relative perfusion profile shows a decrease of the amplitude and the absolute perfusion profile a much smaller increase towards the cortical surface. Considering the draining vein effect on the BOLD signal using model-based spatial convolution, we show that the empirically measured perfusion and BOLD profiles are, in fact, consistent with each other. This study demonstrates that laminar perfusion fMRI in humans is feasible at 7T and that caution must be exercised when interpreting BOLD signal laminar profiles as direct representation of the cortical distribution of neuronal activity.

neuroscience↗

bioRxiv2020

Validating layer-specific VASO across species

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (>=7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated and thus interpretation of such data is confounded. Here we cross-validate layer-dependent VASO fMRI contrast in a preclinical rat model using well established (but invasive) imaging methods in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Through direct comparison of response magnitude, across time, negligible changes in hematocrit ratio during activation (neuronal or vascular) are inferred. Quantified cortical layer profiling is demonstrated and in agreement between both VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical excitatory and inhibitory processing independent of confounding large draining veins which hamper BOLD fMRI studies. While we find increased VASO based CBV reactivity (3.1 {+/-} 1.2 fold increase) in humans compared to rats it is demonstrated that this reflects differences in stimulus design rather than confounds of the VASO signal source. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent fMRI results and should supersede BOLD fMRI as the method of choice in neuroscience application studies. HighlightsO_LIOur goal is to validate layer-specific VASO fMRI with gold standard methods C_LIO_LILayer-specific VASO sequences are implemented for 7T imaging in humans and rats C_LIO_LIComparisons of VASO, optical imaging, and MION confirm the expected contrast origin C_LIO_LISomatosensory stimulation in humans and rats reveal the same layer-fMRI signatures C_LIO_LIWe confirm that VASO is a valid measure to estimate layer-specific neural activity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/219378v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4f9733org.highwire.dtl.DTLVardef@14fccd2org.highwire.dtl.DTLVardef@101edaorg.highwire.dtl.DTLVardef@598bae_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

LAYNII: A software suite for layer-fMRI

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C++ and is distributed open-source and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain layerification and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data. HighlightsO_LIA new software toolbox is introduced for layer-specific functional MRI: LayNii. C_LIO_LILayNii is a suite of command-line executable C++ programs for Linux, Windows, and macOS. C_LIO_LILayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints. C_LIO_LILayNii performs layerification in the native voxel space of functional data. C_LIO_LILayNii performs layer-smoothing, GE-BOLD deveining, QA, and VASO analysis. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/148080v3_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@e12e9org.highwire.dtl.DTLVardef@1fbb564org.highwire.dtl.DTLVardef@41da13org.highwire.dtl.DTLVardef@1545106_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗

bioRxiv2020

Tailored haemodynamic response function increases detection power of fMRI in awake dogs (Canis familiaris)

Functional magnetic resonance imaging (fMRI) of awake and unrestrained dogs (Canis familiaris) has been established as a novel opportunity for comparative neuroimaging, promising important insights into the evolutionary roots of human brain function and cognition. However, data processing and analysis pipelines are often derivatives of methodological standards developed for human neuroimaging, which may be problematic due to profound neurophysiological and anatomical differences between humans and dogs. Here, we explore whether dog fMRI studies would benefit from a tailored dog haemodynamic response function (HRF). In two independent experiments, dogs were presented with different visual stimuli. BOLD signal changes in the visual cortex during these experiments were used for (a) the identification and estimation of a tailored dog HRF, and (b) the independent validation of the resulting dog HRF estimate. Time course analyses revealed that the BOLD signal in the primary visual cortex peaks significantly earlier in dogs compared to humans, while being comparable in shape. Deriving a tailored dog HRF significantly improved the model fit in both experiments, compared to the canonical HRF used in human fMRI. Using the dog HRF yielded significantly increased activation during visual stimulation, extending from the occipital lobe, to the caudal parietal cortex, the bilateral temporal cortex, and into bilateral hippocampal and thalamic regions. In sum, our findings provide robust evidence for an earlier onset of the dog HRF in a visual stimulation paradigm, and suggest that using such an HRF will be important to increase fMRI detection power in canine neuroimaging. By providing the parameters of the tailored dog HRF and related code, we encourage and enable other researchers to validate whether our findings generalize to other sensory modalities and experimental paradigms. HighlightsO_LIDog fMRI typically uses human HRF, but underlying neurophysiology might differ C_LIO_LIV1 BOLD signal peaked earlier in dogs than predicted by the human HRF C_LIO_LITailored dog HRF improved model fit when tested with independent data C_LIO_LIWhole-brain comparisons confirmed increased detection power for tailored dog HRF C_LIO_LIDog fMRI will benefit from increased detection power of tailored HRF C_LI

neuroscience↗

bioRxiv2019

Comparison of BOLD and CBV using 3D EPI and 3D GRASE for cortical layer fMRI at 7T.

PurposeFunctional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging when using standard gradient-echo (GE) EPI sequences. Gradient and Spin Echo (GRASE) BOLD imaging has also shown greater specificity when compared with GE-BOLD.\n\nMethodsHere we directly compare CBV and BOLD contrasts in high-resolution imaging of the primary motor cortex for laminar fMRI in four combinations of signal labeling, VASO (CBV) and BOLD with 3D GE-EPI and zoomed 3D GRASE image readouts.\n\nResultsWe find that both CBV imaging using EPI-VASO and BOLD imaging using GRASE-BOLD, show similar specificity and sensitivity and are thus useful tools for mesoscopic fMRI in the human cortex.\n\nConclusionThese techniques demonstrate sufficient sensitivity and specificity to allow layer-fMRI to be used by neuroscientists in a wide range of investigations of depth-dependent neural circuitry in the human brain.

neuroscience↗

bioRxiv2018

Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits muscles are used for different motor actions such as flexion movements like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for noninvasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging.

neuroscience↗