Laminar fMRI: applications for cognitive neuroscience

The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses

Exploring structure and function of sensory cortex with 7 T MRI

In this paper, we present an overview of 7 Tesla magnetic resonance imaging (MRI) studies of the detailed function and anatomy of sensory areas of the human brain. We discuss the motivation for the studies, with particular emphasis on increasing the spatial resolution of functional MRI (fMRI) using reduced field-of-view (FOV) data acquisitions. MRI at ultra-high-field (UHF) – defined here as 7 T and above – has several advantages over lower field strengths. The intrinsic signal-to-noise ratio (SNR) of images is higher at UHF, and coupled with the increased blood-oxygen-level-dependent (BOLD) signal change, this results in increased BOLD contrast-to-noise ratio (CNR), which can be exploited to improve spatial resolution or detect weaker signals. Additionally, the BOLD signal from the intra-vascular (IV) compartment is relatively diminished compared to lower field strengths. Together, these properties make 7 T functional MRI an attractive proposition for high spatial specificity measures. But with the advantages come some challenges. For example, increased vulnerability to susceptibility-induced geometric distortions and signal loss in EPI acquisitions tend to be much larger. Some of these technical issues can be addressed with currently available tools and will be discussed. We highlight the key methodological considerations for high resolution functional and structural imaging at 7 T. We then present recent data using the high spatial resolution available at UHF in studies of the visual and somatosensory cortex to highlight promising developments in this area

An interplay of feedforward and feedback signals supporting visual cognition

Vast majority of visual cognitive functions from low to high level rely not only on feedforward signals carrying sensory input to downstream brain areas but also on internally-generated feedback signals traversing the brain in the opposite direction. The feedback signals underlie our ability to conjure up internal representations regardless of sensory input – when imagining an object or directly perceiving it. Despite ubiquitous implications of feedback signals in visual cognition, little is known about their functional organization in the brain. Multiple studies have shown that within the visual system the same brain region can concurrently represent feedforward and feedback contents. Given this spatial overlap, (1) how does the visual brain separate feedforward and feedback signals thus avoiding a mixture of the perceived and the imagined? Confusing the two information streams could lead to potentially detrimental consequences. Another body of research demonstrated that feedback connections between two different sensory systems participate in a rapid and effortless signal transmission across them. (2) How do nonvisual signals elicit visual representations? In this work, we aimed to scrutinize the functional organization of directed signal transmission in the visual brain by interrogating these two critical questions. In Studies I and II, we explored the functional segregation of feedforward and feedback signals in grey matter depth of early visual area V1 using 7T fMRI. In Study III we investigated the mechanism of cross-modal generalization using EEG. In Study I, we hypothesized that functional segregation of external and internally-generated visual contents follows the organization of feedforward and feedback anatomical projections revealed in primate tracing anatomy studies: feedforward projections were found to terminate in the middle cortical layer of primate area V1, whereas feedback connections project to the superficial and deep layers. We used high-resolution layer-specific fMRI and multivariate pattern analysis to test this hypothesis in a mental rotation task. We found that rotated contents were predominant at outer cortical depth compartments (i.e. superficial and deep). At the same time perceived contents were more strongly represented at the middle cortical compartment. These results correspond to the previous neuroanatomical findings and identify how through cortical depth compartmentalization V1 functionally segregates rather than confuses external from internally-generated visual contents. For the more precise estimation of signal-by-depth separation revealed in Study I, next we benchmarked three MR-sequences at 7T - gradient-echo, spin-echo, and vascular space occupancy - in their ability to differentiate feedforward and feedback signals in V1. The experiment in Study II consisted of two complementary tasks: a perception task that predominantly evokes feedforward signals and a working memory task that relies on feedback signals. We used multivariate pattern analysis to read out the perceived (feedforward) and memorized (feedback) grating orientation from neural signals across cortical depth. Analyses across all the MR-sequences revealed perception signals predominantly in the middle cortical compartment of area V1 and working memory signals in the deep compartment. Despite an overall consistency across sequences, spin-echo was the only sequence where both feedforward and feedback information were differently pronounced across cortical depth in a statistically robust way. We therefore suggest that in the context of a typical cognitive neuroscience experiment manipulating feedforward and feedback signals at 7T fMRI, spin-echo method may provide a favorable trade-off between spatial specificity and signal sensitivity. In Study III we focused on the second critical question - how are visual representations activated by signals belonging to another sensory modality? Here we built our hypothesis following the studies in the field of object recognition, which demonstrate that abstract category-level representations emerge in the brain after a brief stimuli presentation in the absence of any explicit categorization task. Based on these findings we assumed that two sensory systems can reach a modality-independent representational state providing a universal feature space which can be read out by both sensory systems. We used EEG and a paradigm in which participants were presented with images and spoken words while they were conducting an unrelated task. We aimed to explore whether categorical object representations in both modalities reflect a convergence towards modality-independent representations. We obtained robust representations of objects and object categories in visual and auditory modalities; however, we did not find a conceptual representation shared across modalities at the level of patterns extracted from EEG scalp electrodes in our study. Overall, our results show that feedforward and feedback signals are spatially segregated in the grey matter depth, possibly reflecting a general strategy for implementation of multiple cognitive functions within the same brain region. This differentiation can be revealed with diverse MR-sequences at 7T fMRI, where spin-echo sequence could be particularly suitable for establishing cortical depth-specific effects in humans. We did not find modality-independent representations which, according to our hypothesis, may subserve the activation of visual representations by the signals from another sensory system. This pattern of results indicates that identifying the mechanisms bridging different sensory systems is more challenging than exploring within-modality signal circuitry and this challenge requires further studies. With this, our results contribute to a large body of research interrogating how feedforward and feedback signals give rise to complex visual cognition

Neural Representations of Visual Motion Processing in the Human Brain Using Laminar Imaging at 9.4 Tesla

During natural behavior, much of the motion signal falling into our eyes is due to our own movements. Therefore, in order to correctly perceive motion in our environment, it is important to parse visual motion signals into those caused by self-motion such as eye- or head-movements and those caused by external motion. Neural mechanisms underlying this task, which are also required to allow for a stable perception of the world during pursuit eye movements, are not fully understood. Both, perceptual stability as well as perception of real-world (i.e. objective) motion are the product of integration between motion signals on the retina and efference copies of eye movements. The central aim of this thesis is to examine whether different levels of cortical depth or distinct columnar structures of visual motion regions are differentially involved in disentangling signals related to self-motion, objective, or object motion. Based on previous studies reporting segregated populations of voxels in high level visual areas such as V3A, V6, and MST responding predominantly to either retinal or extra- retinal (‘real’) motion, we speculated such voxels to reside within laminar or columnar functional units. We used ultra-high field (9.4T) fMRI along with an experimental paradigm that independently manipulated retinal and extra-retinal motion signals (smooth pursuit) while controlling for effects of eye-movements, to investigate whether processing of real world motion in human V5/MT, putative MST (pMST), and V1 is associated to differential laminar signal intensities. We also examined motion integration across cortical depths in human motion areas V3A and V6 that have strong objective motion responses. We found a unique, condition specific laminar profile in human area V6, showing reduced mid-layer responses for retinal motion only, suggestive of an inhibitory retinal contribution to motion integration in mid layers or alternatively an excitatory contribution in deep and superficial layers. We also found evidence indicating that in V5/MT and pMST, processing related to retinal, objective, and pursuit motion are either integrated or colocalized at the scale of our resolution. In contrast, in V1, independent functional processes seem to be driving the response to retinal and objective motion on the one hand, and to pursuit signals on the other. The lack of differential signals across depth in these regions suggests either that a columnar rather than laminar segregation governs these functions in these areas, or that the methods used were unable to detect differential neural laminar processing. Furthermore, the thesis provides a thorough analysis of the relevant technical modalities used for data acquisition and data analysis at ultra-high field in the context of laminar fMRI. Relying on our technical implementations we were able to conduct two high-resolution fMRI experiments that helped us to further investigate the laminar organization of self-induced and externally induced motion cues in human high-level visual areas and to form speculations about the site and the mechanisms of their integration

High-Field fMRI for Human Applications: An Overview of Spatial Resolution and Signal Specificity

In the last decade, dozens of 7 Tesla scanners have been purchased or installed around the world, while 3 Tesla systems have become a standard. This increased interest in higher field strengths is driven by a demonstrated advantage of high fields for available signal-to-noise ratio (SNR) in the magnetic resonance signal. Functional imaging studies have additional advantages of increases in both the contrast and the spatial specificity of the susceptibility based BOLD signal. One use of this resultant increase in the contrast to noise ratio (CNR) for functional MRI studies at high field is increased image resolution. However, there are many factors to consider in predicting exactly what kind of resolution gains might be made at high fields, and what the opportunity costs might be. The first part of this article discusses both hardware and image quality considerations for higher resolution functional imaging. The second part draws distinctions between image resolution, spatial specificity, and functional specificity of the fMRI signals that can be acquired at high fields, suggesting practical limitations for attainable resolutions of fMRI experiments at a given field, given the current state of the art in imaging techniques. Finally, practical resolution limitations and pulse sequence options for studies in human subjects are considered

Effects of phase regression on high-resolution functional MRI of the primary visual cortex

High-resolution functional MRI studies have become a powerful tool to non-invasively probe the sub-millimeter functional organization of the human cortex. Advances in MR hardware, imaging techniques and sophisticated post-processing methods have allowed high resolution fMRI to be used in both the clinical and academic neurosciences. However, consensus within the community regarding the use of gradient echo (GE) or spin echo (SE) based acquisition remains largely divided. On one hand, GE provides a high temporal signal-to-noise ratio (tSNR) technique sensitive to both the macro- and micro-vascular signal while SE based methods are more specific to microvasculature but suffer from lower tSNR and specific absorption rate limitations, especially at high field and with short repetition times. Fortunately, the phase of the GE-EPI signal is sensitive to vessel size and this provides a potential avenue to reduce the macrovascular weighting of the signal (phase regression, Menon 2002). In order to determine the efficacy of this technique at high-resolution, phase regression was applied to GE-EPI timeseries and compared to SE-EPI to determine if GE-EPI\u27s specificity to the microvascular compartment improved. To do this, functional data was collected from seven subjects on a neuro-optimized 7 T system at 800 μm isotropic resolution with both GE-EPI and SE-EPI while observing an 8 Hz contrast reversing checkerboard. Phase data from the GE-EPI was used to create a microvasculature-weighted time series (GE-EPI-PR). Anatomical imaging (MP2RAGE) was also collected to allow for surface segmentation so that the functional results could be projected onto a surface. A multi-echo gradient echo sequence was collected and used to identify venous vasculature. The GE-EPI-PR surface activation maps showed a high qualitative similarity with SE-EPI and also produced laminar activity profiles similar to SE-EPI. When the GE-EPI and GE-EPI-PR distributions were compared to SE-EPI it was shown that GE-EPI-PR had similar distribution characteristics to SE-EPI (p \u3c 0.05) across the top 60% of cortex. Furthermore, it was shown that GE-EPI-PR has a higher contrast-to-noise ratio (0.5 ± 0.2, mean ± std. dev. across layers) than SE-EPI (0.27 ± 0.07) demonstrating the technique has higher sensitivity than SE-EPI. Taken together this evidence suggests phase regression is a useful method in low SNR studies such as high-resolution fMRI

On the encoding of natural music in computational models and human brains

This article discusses recent developments and advances in the neuroscience of music to understand the nature of musical emotion. In particular, it highlights how system identification techniques and computational models of music have advanced our understanding of how the human brain processes the textures and structures of music and how the processed information evokes emotions. Musical models relate physical properties of stimuli to internal representations called features, and predictive models relate features to neural or behavioral responses and test their predictions against independent unseen data. The new frameworks do not require orthogonalized stimuli in controlled experiments to establish reproducible knowledge, which has opened up a new wave of naturalistic neuroscience. The current review focuses on how this trend has transformed the domain of the neuroscience of music

Investigating visual and auditory scene feedback to early visual foveal and peripheral cortex using fMRI

No abstract available

Mapping Brain Development and Decoding Brain Activity with Diffuse Optical Tomography

Functional neuroimaging has been used to map brain function as well as decode information from brain activity. However, applications like studying early brain development or enabling augmentative communication in patients with severe motor disabilities have been constrained by extant imaging modalities, which can be challenging to use in young children and entail major tradeoffs between logistics and image quality. Diffuse optical tomography (DOT) is an emerging method combining logistical advantages of optical imaging with enhanced image quality. Here, we developed one of the world’s largest DOT systems for high-performance optical brain imaging in children. From visual cortex activity in adults, we decoded the locations of checkerboard visual stimuli, e.g. localizing a 60 degree wedge rotating through 36 positions with an error of 25.8±24.7 degrees. Using animated movies as more child-friendly stimuli, we mapped reproducible responses to speech and faces with DOT in awake, typically developing 1-7 year-old children and adults. We then decoded with accuracy significantly above chance which movie a participant was watching or listening to from DOT data. This work lays a valuable foundation for ongoing research with wearable imaging systems and increasingly complex algorithms to map atypical brain development and decode covert semantic information in clinical populations

Nonparametric statistical inference for functional brain information mapping

An ever-increasing number of functional magnetic resonance imaging (fMRI) studies are now using information-based multi-voxel pattern analysis (MVPA) techniques to decode mental states. In doing so, they achieve a significantly greater sensitivity compared to when they use univariate analysis frameworks. Two most prominent MVPA methods for information mapping are searchlight decoding and classifier weight mapping. The new MVPA brain mapping methods, however, have also posed new challenges for analysis and statistical inference on the group level. In this thesis, I discuss why the usual procedure of performing t-tests on MVPA derived information maps across subjects in order to produce a group statistic is inappropriate. I propose a fully nonparametric solution to this problem, which achieves higher sensitivity than the most commonly used t-based procedure. The proposed method is based on resampling methods and preserves the spatial dependencies in the MVPA-derived information maps. This enables to incorporate a cluster size control for the multiple testing problem. Using a volumetric searchlight decoding procedure and classifier weight maps, I demonstrate the validity and sensitivity of the new approach using both simulated and real fMRI data sets. In comparison to the standard t-test procedure implemented in SPM8, the new results showed a higher sensitivity and spatial specificity. The second goal of this thesis is the comparison of the two widely used information mapping approaches -- the searchlight technique and classifier weight mapping. Both methods take into account the spatially distributed patterns of activation in order to predict stimulus conditions, however the searchlight method solely operates on the local scale. The searchlight decoding technique has furthermore been found to be prone to spatial inaccuracies. For instance, the spatial extent of informative areas is generally exaggerated, and their spatial configuration is distorted. In this thesis, I compare searchlight decoding with linear classifier weight mapping, both using the formerly proposed non-parametric statistical framework using a simulation and ultra-high-field 7T experimental data. It was found that the searchlight method led to spatial inaccuracies that are especially noticeable in high-resolution fMRI data. In contrast, the weight mapping method was more spatially precise, revealing both informative anatomical structures as well as the direction by which voxels contribute to the classification. By maximizing the spatial accuracy of ultra-high-field fMRI results, such global multivariate methods provide a substantial improvement for characterizing structure-function relationships