Introduction to fMRI: experimental design and data analysis

This provides an introduction to functional MRI, experimental design and data analysis procedures using statistical parametric mapping approach

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

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

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

Evaluation of acoustic noise in magnetic resonance imaging

Magnetic resonance imaging (MRI) is a technique in which strong static and dynamic magnetic fields are used to create virtual slices of the human body. The process of MR imaging is associated with several health and safety issues which may negatively affect patient and radiological health workers. Potentially hazardous are biological effects of both the static and dynamic magnetic fields, the torques of the magnetic fields acting on ferromagnetic objects, thermal effects, and the negative effects of high acoustic sound pressures. The subject of this dissertation is the evaluation and modification of acoustic noise generated during MRI