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The 9.4T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7T. This article reviews some of the 9.4T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4T. Our experience shows that, while considerable effort was required compared to our 7T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern analysis (MVPA), we demonstrate cortical depth-specific representations in areas V3A and V7 as indicated by stronger pattern responses for correlated than for anticorrelated stimuli in upper rather than deeper layers. Examining informational connectivity, we find higher feedforward layer-to-layer connectivity for correlated than anticorrelated stimuli between V3A and V7. Further, we observe disparity-specific feedback from V3A to V1 and from V7 to V3A. Our findings provide evidence for the role of V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures. SIGNIFICANCE STATEMENT Binocular vision plays a significant role in supporting our interactions with the surrounding environment. The fine-scale neural mechanisms that underlie the brain9s skill in extracting 3D structures from binocular signals are poorly understood. Here, we capitalize on recent advances in ultra-high-field functional imaging to interrogate human brain circuits involved in 3D perception at submillimeter resolution. We provide evidence for the role of area V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures from binocular signals. These fine-scale measurements help bridge the gap between animal neurophysiology and human fMRI studies investigating cross-scale circuits, from micro circuits to global brain networks for 3D perception.

Neuroimaging studies have suggested that hMT+ encodes global motion interpretation, but this contradicts the notion that BOLD activity mainly reflects neuronal input. While measuring fMRI responses at 7 Tesla, we used an ambiguous moving stimulus, yielding the perception of two incoherently moving surfaces—component motion—or only one coherently moving surface—pattern motion, to induce perceptual fluctuations and identify perceptual organization size‐matched domains in hMT+. Then, moving gratings, exactly matching either the direction of component or pattern motion percepts of the ambiguous stimulus, were shown to the participants to investigate whether response properties reflect the input or decision. If hMT+ responses reflect the input, component motion domains (selective to incoherent percept) should show grating direction stimulus‐dependent changes, unlike pattern motion domains (selective to the coherent percept). This hypothesis is based on the known direction‐selective nature of inputs in component motion perceptual domains versus non‐selectivity in pattern motion perceptual domains. The response amplitude of pattern motion domains did not change with grating direction (consistently with their non‐selective input), in contrast to what happened for the component motion domains (consistently with their selective input). However, when we analyzed relative ratio measures they mirrored perceptual interpretation. These findings are consistent with the notion that patterns of BOLD responses reflect both sensory input and perceptual read‐out., Sousa et al. used an ambiguous moving stimulus, yielding the perception of two incoherently moving surfaces—component motion—or only one coherently moving surface—pattern motion, to induce perceptual fluctuations and identify perceptual organization size‐matched domains in hMT+. Their findings are consistent with the notion that patterns of BOLD responses reflect both sensory input and perceptual read‐out.

Adapting to the environment statistics by reducing brain responses to repetitive sensory information is key for efficient information processing. Yet, the fine-scale computations that support this adaptive processing in the human brain remain largely unknown. Here, we capitalize on the sub-millimetre resolution afforded by ultra-high field imaging to examine BOLD-fMRI signals across cortical depth and discern competing hypotheses about the brain mechanisms (feedforward vs. feedback) that mediate adaptive visual processing. We demonstrate suppressive recurrent processing within visual cortex, as indicated by stronger BOLD decrease in superficial than middle and deeper layers for gratings that were repeatedly presented at the same orientation. Further, we show dissociable connectivity mechanisms for adaptive processing: enhanced feedforward connectivity within visual cortex, while feedback occipito-parietal connectivity, reflecting top-down influences on visual processing. Our findings provide evidence for a circuit of local recurrent and feedback interactions that mediate rapid brain plasticity for adaptive information processing.

The ability to measure functional brain responses non-invasively with ultra high field MRI (7 T and above) represents a unique opportunity in advancing our understanding of the human brain. Compared to lower fields (3 T and below), ultra high field MRI has an increased sensitivity, which can be used to acquire functional images with greater spatial resolution, and greater specificity of the blood oxygen level dependent (BOLD) signal to the underlying neuronal responses. Together, increased resolution and specificity enable investigating brain functions at a submillimeter scale, which so far could only be done with invasive techniques. At this mesoscopic spatial scale, perception, cognition and behavior can be probed at the level of fundamental units of neural computations, such as cortical columns, cortical layers, and subcortical nuclei. This represents a unique and distinctive advantage that differentiates ultra high from lower field imaging and that can foster a tighter link between fMRI and computational modeling of neural networks. So far, functional brain mapping at submillimeter scale has focused on the processing of sensory information and on well-known systems for which extensive information is available from invasive recordings in animals. It remains an open challenge to extend this methodology to uniquely human functions and, more generally, to systems for which animal models may be problematic. To succeed, the possibility to acquire high-resolution functional data with large spatial coverage, the availability of computational models of neural processing as well as accurate biophysical modeling of neurovascular coupling at mesoscopic scale all appear necessary.

Following rapid technological advances, ultra-high field functional MRI (fMRI) enables exploring correlates of neuronal population activity at an increasing spatial resolution. However, as the fMRI blood-oxygenation-level-dependent (BOLD) contrast is a vascular signal, the spatial specificity of fMRI data is ultimately determined by the characteristics of the underlying vasculature. At 7T, fMRI measurement parameters determine the relative contribution of the macro- and microvasculature to the acquired signal. Here we investigate how these parameters affect relevant high-end fMRI analyses such as encoding, decoding, and submillimeter mapping of voxel preferences in the human auditory cortex. Specifically, we compare a T2* weighted fMRI dataset, obtained with 2D gradient echo (GE) EPI, to a predominantly T2 weighted dataset obtained with 3D GRASE. We first investigated the decoding accuracy based on two encoding models that represented different hypotheses about auditory cortical processing. This encoding/decoding analysis profited from the large spatial coverage and sensitivity of the T2* weighted acquisitions, as evidenced by a significantly higher prediction accuracy in the GE-EPI dataset compared to the 3D GRASE dataset for both encoding models. The main disadvantage of the T2* weighted GE-EPI dataset for encoding/decoding analyses was that the prediction accuracy exhibited cortical depth dependent vascular biases. However, we propose that the comparison of prediction accuracy across the different encoding models may be used as a post processing technique to salvage the spatial interpretability of the GE-EPI cortical depth-dependent prediction accuracy. Second, we explored the mapping of voxel preferences. Large-scale maps of frequency preference (i.e., tonotopy) were similar across datasets, yet the GE-EPI dataset was preferable due to its larger spatial coverage and sensitivity. However, submillimeter tonotopy maps revealed biases in assigned frequency preference and selectivity for the GE-EPI dataset, but not for the 3D GRASE dataset. Thus, a T2 weighted acquisition is recommended if high specificity in tonotopic maps is required. In conclusion, different fMRI acquisitions were better suited for different analyses. It is therefore critical that any sequence parameter optimization considers the eventual intended fMRI analyses and the nature of the neuroscience questions being asked.

The advent of ultra-high field functional magnetic resonance imaging (fMRI) has greatly facilitated submillimeter resolution acquisitions (voxel volume below (1 mm³)), allowing the investigation of cortical columns and cortical depth dependent (i.e. laminar) structures in the human brain. Advanced data analysis techniques are essential to exploit the information in high resolution functional measures. In this article, we use recent, exemplary 9.4 T human functional and anatomical data to review the advantages and disadvantages of (1) pooling high resolution data across regions of interest for cortical depth profile analysis, (2) pooling across cortical depths for mapping patches of cortex while discarding depth-dependent (i.e. columnar) effects, and (3) isotropic sampling without pooling to assess individual voxel’s responses. A set of cortical depth meshes may be a solution to sampling information tangentially while keeping correspondence across depths. For quantitative analysis of the spatial organization in fine-grained structures, a cortical grid approach is advantageous. We further extend this general framework by combining it with a previously introduced cortical layer volume-preserving (equi-volume) approach. This framework can readily accommodate the research questions which allow for spatial smoothing within or across layers. We demonstrate and discuss that equi-volume sampling yields a slight advantage over equidistant sampling given the current limitations of fMRI voxel size, participant motion, coregistration and segmentation. Our 9.4 T human anatomical and functional data indicate the advantage over lower fields including 7 T and demonstrate the practical applicability of T2* and T2-weighted fMRI acquisitions., Highlights • High resolution regular cortical grids are advantageous for local applications. • Equi-volume sampling is slightly advantageous over equidistant sampling in-vivo. • Isotropic submillimeter cortical sampling without spatial pooling requires high SNR. • 9.4 T human T2 and T2* BOLD fMRI are practically feasible and provide high SNR. • 9.4 T T2*-weighted 0.35 mm iso. res. anatomical images for laminar contrast in vivo.

Summary Ultra-high field (UHF) neuroimaging affords the sub-millimeter resolution that allows researchers to interrogate brain computations at a finer scale than that afforded by standard fMRI techniques. Here, we present a step-by-step protocol for using UHF imaging (Siemens Terra 7T scanner) to measure activity in the human brain. We outline how to preprocess the data using a pipeline that combines tools from SPM, FreeSurfer, ITK-SNAP, and BrainVoyager and correct for vasculature-related confounders to improve the spatial accuracy of the fMRI signal. For complete details on the use and execution of this protocol, please refer to Jia et al. (2020) and Zamboni et al. (2020)., Graphical abstract, Highlights • Protocol for using ultra-high field imaging to measure activity in the human brain • Defining cortical layers using high-resolution anatomical scans • Preprocessing functional brain imaging data across cortical depth • Correcting for vasculature-related confounds to improve spatial specificity, Ultra-high field (UHF) neuroimaging affords the sub-millimeter resolution that allows researchers to interrogate brain computations at a finer scale than that afforded by standard fMRI techniques. Here, we present a step-by-step protocol for using UHF imaging (Siemens Terra 7T scanner) to measure activity in the human brain. We outline how to preprocess the data using a pipeline that combines tools from SPM, FreeSurfer, ITK-SNAP, and BrainVoyager and correct for vasculature-related confounders to improve the spatial accuracy of the fMRI signal.

The role of long-range integration mechanisms underlying visual perceptual binding and their link to interhemispheric functional connectivity, as measured by fMRI, remains elusive. Only inferences on anatomical organization from resting state data paradigms not requiring coherent binding have been achieved. Here, we used a paradigm that allowed us to study such relation between perceptual interpretation and functional connectivity under bistable interhemispheric binding vs. non-binding of visual surfaces. Binding occurs by long-range perceptual integration of motion into a single object across hemifields and non-binding reflects opponent segregation of distinct moving surfaces into each hemifield. We hypothesized that perceptual integration vs. segregation of surface motion, which is achieved in visual area hMT+, is modulated by changes in interhemispheric connectivity in this region. Using 7T fMRI, we found that perceptual long-range integration of bistable motion can be tracked by changes in interhemispheric functional connectivity between left/right hMT+. Increased connectivity was tightly related with long-range perceptual integration. Our results indicate that hMT+ interhemispheric functional connectivity reflects perceptual decision, suggesting its pivotal role on long-range disambiguation of bistable physically constant surface motion. We reveal for the first time, at the scale of fMRI, a relation between interhemispheric functional connectivity and decision based perceptual binding.

Significance Existing knowledge of how cortical responses link to conscious content in humans is either inferred from animal models or from human studies limited by lower spatial resolution. While previous studies could relate distinct categorical percepts (faces vs. places) to signal differences across brain areas, measuring responses at submillimeter resolution allowed us to link subcategory conscious percepts (vertical vs. horizontal motion) to amplitude changes of separate populations within the same brain area. Furthermore, preferences for horizontal and vertical motion were organized into columnar clusters. We pave the way for future studies investigating if columnar clusters represent subcategorical distinctions in conscious content different from motion or in high-level perceptual and cognitive phenomena., The specific contents of human consciousness rely on the activity of specialized neurons in cerebral cortex. We hypothesized that the conscious experience of a specific visual motion axis is reflected in response amplitudes of direction-selective clusters in the human motion complex. Using submillimeter fMRI at ultrahigh field (7 T) we identified fine-grained clusters that were tuned to either horizontal or vertical motion presented in an unambiguous motion display. We then recorded their responses while human observers reported the perceived axis of motion for an ambiguous apparent motion display. Although retinal stimulation remained constant, subjects reported recurring changes between horizontal and vertical motion percepts every 7 to 13 s. We found that these perceptual states were dissociatively reflected in the response amplitudes of the identified horizontal and vertical clusters. We also found that responses to unambiguous motion were organized in a columnar fashion such that motion preferences were stable in the direction of cortical depth and changed when moving along the cortical surface. We suggest that activity in these specialized clusters is involved in tracking the distinct conscious experience of a particular motion axis.

Summary Learning and experience are critical for translating ambiguous sensory information from our environments to perceptual decisions. Yet evidence on how training molds the adult human brain remains controversial, as fMRI at standard resolution does not allow us to discern the finer scale mechanisms that underlie sensory plasticity. Here, we combine ultra-high-field (7T) functional imaging at sub-millimeter resolution with orientation discrimination training to interrogate experience-dependent plasticity across cortical depths that are known to support dissociable brain computations. We demonstrate that learning alters orientation-specific representations in superficial rather than middle or deeper V1 layers, consistent with recurrent plasticity mechanisms via horizontal connections. Further, learning increases feedforward rather than feedback layer-to-layer connectivity in occipito-parietal regions, suggesting that sensory plasticity gates perceptual decisions. Our findings reveal finer scale plasticity mechanisms that re-weight sensory signals to inform improved decisions, bridging the gap between micro- and macro-circuits of experience-dependent plasticity., Highlights • Discrimination training alters orientation representations in superficial V1 layers • Orientation-specific V1 plasticity is independent of task context • Discrimination training alters orientation representations in middle IPS layers • Learning enhances feedforward connectivity from visual to parietal cortex, Using high-field laminar fMRI, Jia et al. show that learning alters orientation-specific representations in superficial V1 layers and enhances connectivity from visual to parietal cortex, suggesting that recurrent visual plasticity and feedforward connectivity gate perceptual decision making.

Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning, yet comparable evidence in humans is scarce. Moreover, whether the spotlight operates in human midbrain is unknown. To address these issues, we studied the spectral tuning of frequency channels in human PAC and inferior colliculus (IC), using 7-T functional magnetic resonance imaging (FMRI) and frequency mapping, while participants focused on different frequency-specific sounds. We found that shifts in frequency-specific attention alter the response gain, but not tuning profile, of PAC frequency channels. The gain modulation was strongest in low-frequency channels and varied near-monotonically across the tonotopic axis, giving rise to the attentional spotlight. We observed less prominent, non-tonotopic spatial patterns of attentional modulation in IC. These results indicate that the frequency-specific attentional spotlight in human PAC as measured with FMRI arises primarily from tonotopic gain modulation, rather than adapted frequency tuning. Moreover, frequency-specific attentional modulation of afferent sound processing in human IC seems to be considerably weaker, suggesting that the spotlight diminishes toward this lower-order processing stage. Our study sheds light on how the human auditory pathway adapts to the different demands of selective hearing.

Purpose To evaluate the use of variable flip angle refocusing pulse trains in single-shot three-dimensional gradient and spin-echo (3D-GRASE) to reduce blurring and increase the spatial coverage for high spatial resolution T2-weighted functional MRI at 7 Tesla. Methods Variable flip angle refocusing schemes in 3D-GRASE were calculated based on extended phase graph theory. The blurring along the slice (partition) direction was evaluated in simulations, as well as phantom and in vivo experiments. Furthermore, temporal stability and functional sensitivity at 0.8 mm isotropic resolution were assessed. Results Variable flip angle refocusing schemes yielded significantly reduced blurring compared with conventional refocusing schemes, with the full width at half maximum being approximately 30–40% narrower. Simultaneously, spatial coverage could be increased by 80%. The temporal signal-to-noise ratio was slightly reduced, but functional sensitivity was largely maintained due to increased functional contrast in the variable flip angle acquisitions. Signal-to-noise ratio and functional sensitivity were reduced more strongly in areas with insufficient radiofrequency transmission indicating higher sensitivity to experimental imperfections. Conclusion Variable flip angle refocusing schemes increase usability of 3D-GRASE for high-resolution functional MRI by reducing blurring and allowing increased spatial coverage. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

A sound of interest may be tracked amid other salient sounds by focusing attention on its characteristic features including its frequency. Functional magnetic resonance imaging findings have indicated that frequency representations in human primary auditory cortex (AC) contribute to this feat. However, attentional modulations were examined at relatively low spatial and spectral resolutions, and frequency-selective contributions outside the primary AC could not be established. To address these issues, we compared blood oxygenation level-dependent (BOLD) responses in the superior temporal cortex of human listeners while they identified single frequencies versus listened selectively for various frequencies within a multifrequency scene. Using best-frequency mapping, we observed that the detailed spatial layout of attention-induced BOLD response enhancements in primary AC follows the tonotopy of stimulus-driven frequency representations-analogous to the "spotlight" of attention enhancing visuospatial representations in retinotopic visual cortex. Moreover, using an algorithm trained to discriminate stimulus-driven frequency representations, we could successfully decode the focus of frequency-selective attention from listeners' BOLD response patterns in nonprimary AC. Our results indicate that the human brain facilitates selective listening to a frequency of interest in a scene by reinforcing the fine-grained activity pattern throughout the entire superior temporal cortex that would be evoked if that frequency was present alone.

Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. Methods: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. Results: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. Discussion: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

PURPOSE: To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla.METHODS: A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using [Formula: see text] mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic.RESULTS: The transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic.CONCLUSION: The 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.