Search

Electrocorticography (ECoG) is typically employed to accurately identify the seizure focus as well as the location of brain functions to be spared during surgical resection in participants with drug-resistant epilepsy. Increasingly, this technique has become a powerful tool to map cognitive functions onto brain regions. Cortical mapping is more commonly investigated with functional MRI (fMRI), which measures blood-oxygen level dependent (BOLD) changes induced by neuronal activity. The multimodal integration between typical 3T fMRI activity maps and ECoG measurements can provide unique insight into the spatiotemporal aspects of cognition. However, the optimal integration of fMRI and ECoG requires fundamental insight into the spatial smoothness of the BOLD signal under each electrode. Here we use ECoG as ground truth for the extent of activity, as each electrode is thought to record from the cortical tissue directly underneath the contact, to estimate the spatial smoothness of the associated BOLD response at 3T fMRI. We compared the high-frequency broadband (HFB) activity recorded with ECoG while participants performed a motor task. Activity maps were obtained with fMRI at 3T for the same task in the same participant prior to surgery. We then correlated HFB power with the fMRI BOLD signal change in the area around each electrode. This latter measure was quantified by applying a 3D Gaussian kernel of varying width (sigma between 1 mm and 20 mm) to the fMRI maps including only gray-matter. We found that the correlation between HFB and BOLD activity increased sharply up to the point when the kernel width was set to 4 mm, which we defined as the kernel width of maximal spatial specificity. After this point, as the kernel width increased, the highest level of explained variance was reached at a kernel width of 9 mm for most participants. Intriguingly, maximal specificity was also limited to 4 mm for low-frequency bands, such as alpha and beta, but the kernel width with the highest explained variance was less spatially limited than the HFB. In summary, spatial specificity is limited to a kernel width of 4 mm but explained variance keeps on increasing as you average over more and more voxels containing the relatively noisy BOLD signal. Future multimodal studies should choose the kernel width based on their research goal. For maximal spatial specificity, ECoG electrodes are best compared to 3T fMRI with a kernel width of 4 mm. When optimizing the correlation between modalities, highest explained variance can be obtained at larger kernel widths of 9 mm, at the expense of spatial specificity. Finally, we release the complete pipeline so that researchers can estimate the most appropriate kernel width from their multimodal datasets., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

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. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. 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 non-invasive 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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The rapid developments in functional MRI (fMRI) acquisition methods and hardware technologies in recent years, particularly at high field (≥7 T), have enabled unparalleled visualization of functional detail at a laminar or columnar level, bringing fMRI close to the intrinsic resolution of brain function. These advances highlight the potential of high resolution fMRI to be a valuable tool to study the fundamental processing performed in cortical micro-circuits, and their interactions such as feedforward and feedback processes. Notably, because fMRI measures neuronal activity via hemodynamics, the ultimate resolution it affords depends on the spatial specificity of hemodynamics to neuronal activity at a detailed spatial scale, and by the evolution of this specificity over time. Several laminar (≤1 mm spatial resolution) fMRI studies have examined spatial characteristics of the measured hemodynamic signals across cortical depth, in light of understanding or improving the spatial specificity of laminar fMRI. Few studies have examined temporal features of the hemodynamic response across cortical depth. Temporal features of the hemodynamic response offer an additional means to improve the specificity of fMRI, and could help target neuronal processes and neurovascular coupling relationships across laminae, for example by differences in the onset times of the response across cortical depth. In this review, we discuss factors that affect the timing of neuronal and hemodynamic responses across laminae, touching on the neuronal laminar organization, and focusing on the laminar vascular organization. We provide an overview of hemodynamics across the cortical vascular tree based on optical imaging studies, and review temporal aspects of hemodynamics that have been examined across cortical depth in high spatiotemporal resolution fMRI studies. Last, we discuss the limits and potential of high spatiotemporal resolution fMRI to study laminar neurovascular coupling and neuronal processes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The relevance of human primary motor cortex (M1) for motor actions has long been established. However, it is still unknown how motor actions are represented, and whether M1 contains an ordered somatotopy at the mesoscopic level. In the current study we show that a detailed within-limb somatotopy can be obtained in M1 during finger movements using Gaussian population Receptive Field (pRF) models. Similar organizations were also obtained for primary somatosensory cortex (S1), showing that individual finger representations are interconnected throughout sensorimotor cortex. The current study additionally estimates receptive field sizes of neuronal populations, showing differences between finger digit representations, between M1 and S1, and additionally between finger digit flexion and extension. Using the Gaussian pRF approach, the detailed somatotopic organization of M1 can be obtained including underlying characteristics, allowing for the in-depth investigation of cortical motor representation and sensorimotor integration., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Human MRI scanners at ultra-high magnetic field strengths of 7 T and higher are increasingly available to the neuroscience community. A key advantage brought by ultra-high field MRI is the possibility to increase the spatial resolution at which data is acquired, with little reduction in image quality. This opens a new set of opportunities for neuroscience, allowing investigators to map the human cortex at an unprecedented level of detail. In this review, we present recent work that capitalizes on the increased signal-to-noise ratio available at ultra-high field and discuss the theoretical advances with a focus on sensory and motor systems neuroscience. Further, we review research performed at sub-millimeter spatial resolution and discuss the limits and the potential of ultra-high field imaging for structural and functional imaging in human cortex. The increased spatial resolution achievable at ultra-high field has the potential to unveil the fundamental computations performed within a given cortical area, ultimately allowing the visualization of the mesoscopic organization of human cortex at the functional and structural level., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Deciphering the direction of information flow is critical to understand the brain. Data from non-human primate histology shows that connections between lower to higher areas (e.g. retina→V1), and between higher to lower areas (e.g. V1←V2) can be dissociated based upon the distribution of afferent synapses at the laminar level. Ultra-high field scanners opened up the possibility to image brain structure and function at an unprecedented level of detail. Taking advantage of the increased spatial resolution available, it could theoretically be possible to disentangle activity from different cortical depths from human cerebral cortex, separately studying different compartments across depth. Here we use half-millimeter human functional and structural magnetic resonance imaging (fMRI, MRI) to derive laminar profiles in early visual cortex using a paradigm known to elicit two separate responses originating from an excitatory and a suppressive source, avoiding any contamination due to blood-stealing. We report the shape of laminar blood level oxygenation level dependent (BOLD) profiles from the excitatory and suppressive conditions. We analyse positive and negative %BOLD laminar profiles with respect to the dominating linear trend towards the pial surface, a confounding feature of gradient echo BOLD fMRI, and examine the correspondence with the anatomical landmark of input-related signals in primary visual cortex, the stria of Gennari., (Copyright © 2017. Published by Elsevier Inc.)

Changes in brain neuronal activity are reflected by hemodynamic responses mapped through Blood Oxygenation Level Dependent (BOLD) functional magnetic resonance imaging (fMRI), a primary tool to measure brain functioning non-invasively. However, the exact relationship between hemodynamics and neuronal function is still a matter of debate. Here, we combine 3T BOLD fMRI and High Frequency Band (HFB) electrocorticography (ECoG) signals to investigate the relationship between neuronal activity and hemodynamic responses in the human Middle Temporal complex (hMT+), a higher order brain area involved in visual motion processing. We modulated the ECoG HFB and fMRI BOLD responses with a visual stimulus moving at different temporal frequencies, and compared measured BOLD responses to estimated BOLD responses that were predicted from the temporal profile of the HFB power change. We show that BOLD responses under an electrode over hMT+ can be well predicted not only be the strength of the neuronal response but also by the temporal profile of the HFB responses recorded by this electrode. Our results point to a linear relationship between BOLD and neuronal activity in hMT+, extending previous findings on primary cortex to higher order cortex., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Receptive fields (RFs) in visual cortex are organized in antagonistic, center-surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina. We use sub-millimeter resolution functional MRI at 7Tesla and population receptive field (pRF) modeling to investigate the pRF properties in primary visual cortex (V1) across cortical depth. pRF size varies according to a U-shaped function, indicating smaller pRF center size in the middle compared to superficial and deeper intra-cortical portions of V1, consistent with non-human primate neurophysiological measurements. Moreover, a similar U-shaped function is also observed for pRF surround size. However, pRF center-surround ratio remains constant across cortical depth. Simulations suggest that this pattern of results can be directly linked to the flow of signals across cortical depth, with the visual input reaching the middle of cortical depth and then spreading towards superficial and deeper layers of V1. Conversely, blood-oxygenation-level-dependent (BOLD) signal amplitude increases monotonically towards the pial surface, in line with the known vascular organization across cortical depth. Independent estimates of the haemodynamic response function (HRF) across cortical depth show that the center-surround pRF size estimates across cortical depth cannot be explained by variations in the full-width half maximum (FWHM) of the HRF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The human cerebral cortex is characterized by a number of features that are not uniformly distributed, such as the presence of multiple cytoarchitectonic elements and of myelinated layers running tangentially to the cortex surface. The presence and absence of these features are the basis of the parcellation of the cerebral cortex in several areas. A number of areas show myelin increases localized within the cortex, e.g., the stria of Gennari located in layer IV of the primary visual cortex. Sub-millimeter MRI can resolve myelin variations across the human cortex and may allow in vivo parcellation of these brain areas. Here, we image within-area myelination. We modified a T1-weighted (T1-w) MPRAGE sequence to enhance myelin visualization within the cortex. First, we acquired images from an ex vivo sample, and compared MRI laminar profiles from calcarine (corresponding to primary visual cortex) and extra-calcarine areas with histology sections from the same locations. Laminar profiles between myelin stained sections and the T1-w images were similar both in calcarine as well as extra-calcarine cortex. In calcarine cortex, the profile reveals the stria of Gennari. In extra-calcarine cortex, a similar profile exists which we suggest corresponds to the lines of Baillarger. Next, we adapted the same sequence to image within-area myelination in vivo. Also in in vivo data, we discriminated similar laminar profiles in calcarine and extra-calcarine cortex, extending into parietal and frontal lobes. We argue that this myelin pattern outside the calcarine cortex represents the lines of Baillarger., (Copyright © 2016 Elsevier Inc. All rights reserved.)

High resolution BOLD fMRI has the potential to map activation patterns of small neuronal populations at the scale of cortical columns. However, BOLD fMRI does not measure neuronal activity, but only a correlate thereof, since it measures blood dynamics. To confirm that BOLD activation maps reflect neuronal population activity patterns, a direct comparison with neuro-electrophysiological data from the same cortical patch is necessary. Here, we compare BOLD activation patterns obtained with fMRI at 7 T to electrophysiological patterns obtained with implanted high density electrocorticography (ECoG) grids in the same patch of human sensorimotor cortex, and with similar resolution (1.5mm). We used high spatially sampled high-frequency broadband (HFB) power from ECoG, which reflects local neuronal population activity. The spatial distribution of 7 T BOLD activation matched the spatial distribution of ECoG HFB-power changes in the covered patch of sensorimotor cortex. BOLD fMRI activation foci were located within 1-3mm of the HFB-power ECoG foci. Both methods distinguished individual finger movement activation within a 1cm cortical patch, revealing a topographical medial to lateral layout for the little finger to index to thumb. These findings demonstrate that the BOLD signal at 7 T is strongly correlated with the underlying electrophysiology, and is capable of discriminating patterns of neuronal population activity at a millimeter scale. The results further indicate the utility of 7 T fMRI for investigation of intra-area organization of function and network dynamics., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The nature and origin of fMRI resting state fluctuations and connectivity are still not fully known. More detailed knowledge on the relationship between resting state patterns and brain function may help to elucidate this matter. We therefore performed an in depth study of how resting state fluctuations map to the well known architecture of the visual system. We investigated resting state connectivity at both a fine and large scale within and across visual areas V1, V2 and V3 in ten human subjects using a 7Tesla scanner. We found evidence for several coexisting and overlapping connectivity structures at different spatial scales. At the fine-scale level we found enhanced connectivity between the same topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to the contralateral functional homologue, and to a lesser extent enhanced connectivity between iso-eccentric locations within the same visual area. However, by far the largest proportion of the resting state fluctuations occurred within large-scale bilateral networks. These large-scale networks mapped to some extent onto the architecture of the visual system and could thereby obscure fine-scale connectivity. In fact, most of the fine-scale connectivity only became apparent after the large-scale network fluctuations were filtered from the timeseries. We conclude that fMRI resting state fluctuations in the visual cortex may in fact be a composite signal of different overlapping sources. Isolating the different sources could enhance correlations between BOLD and electrophysiological correlates of resting state activity., (© 2013 Elsevier Inc. All rights reserved.)

Magnetic susceptibility based (T(2)* weighted) contrast in MRI at high magnetic field strength is of great value in research on brain structure and cortical architecture, but its use is hampered by the low signal-to-noise ratio (SNR) efficiency of the conventional spoiled gradient echo sequence (GRE) leading to long scan times even for a limited number of slices. In this work, we show that high resolution (0.5mm isotropic) T(2)* weighted images of the whole brain can be obtained in 6min by utilizing the high SNR efficiency of echo-planar imaging (EPI). A volumetric (3D) EPI protocol is presented and compared to conventional 3D GRE images acquired with the same resolution, amount of T(2)* weighting, and imaging duration. Spatial coverage in 3D EPI was increased by a factor of 4.5 compared to 3D GRE, while also the SNR was increased by a factor of 2. Image contrast for both magnitude and phase between gray and white matter was similar for both sequences, with enhanced conspicuity of anatomic details in the 3D EPI images due to the increased SNR. Even at 7T, image blurring and distortion is limited if the EPI train length remains short (not longer than the T(2)* of the imaged tissue). 3D EPI provides steps (speed, whole brain coverage, and high isotropic resolution) that are necessary to utilize the benefits of high field MRI in research that employs T(2)* weighted imaging., (Copyright © 2011 Elsevier Inc. All rights reserved.)