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

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

A computational approach to motivated behaviour and apathy

The loss of motivation and goal-directed behaviour is characteristic of apathy. Across a wide range of neuropsychiatric disorders, including Huntington’s disease (HD), apathy is poorly understood, associated with significant morbidity, and is hard to treat. One of the challenges in understanding the neural basis of apathy is moving from phenomenology and behavioural dysfunction to neural circuits in a principled manner. The computational framework offers one such approach. I adopt this framework to better understand motivated behaviour and apathy in four complementary projects. At the heart of many apathy formulations is impaired self-initiation of goal-directed behaviour. An influential computational theory proposes that “opportunity cost”, the amount of reward we stand to lose by not taking actions per unit time, is a key variable in governing the timing of self-initiated behaviour. Using a novel task, I found that free-operant behaviour in healthy participants both in laboratory conditions and in online testing, conforms to predictions of this computational model. Furthermore, in both studies I found that in younger adults sensitivity to opportunity cost predicted behavioural apathy scores. Similar pilot results were found in a cohort of patients with HD. These data suggest that opportunity cost may be an important computational variable relevant for understanding a core feature of apathy – the timing of self-initiated behaviour. In my second project, I used a reinforcement learning paradigm to probe for early dysfunction in a cohort of HD gene carriers approximately 25 years from clinical onset. Based on empirical data and computational models of basal ganglia function I predicted that asymmetry in learning from gains and losses may be an early feature of carrying the HD gene. As predicted, in this task fMRI study, HD gene carriers demonstrated an exaggerated neural response to gains as compared to losses. Gene carriers also differed in the neural response to expected value suggesting that carrying the HD gene is associated with altered processing of valence and value decades from onset. Finally, based on neurocomputational models of basal ganglia pathway function, I tested the hypothesis that apathy in HD would be associated with the involvement of the direct pathway. Support for this hypothesis was found in two related projects. Firstly, using data from a large international HD cohort study, I found that apathy was associated with motor features of the disease thought to represent direct pathway involvement. Secondly, I tested this hypothesis in vivo using resting state fMRI data and a model of basal ganglia connectivity in a large peri-manifest HD cohort. In keeping with my predictions, whilst emerging motor signs were associated with changes in the indirect pathway, apathy scores were associated with connectivity changes in the direct pathway connectivity within my model. For patients with apathy across neuropsychiatry there is an urgent need to understand the neural basis of motivated behaviour in order to develop novel therapies. In this thesis, I have used a computational framework to develop and test a range of hypotheses to advance this understanding. In particular, I have focussed on the computational factors which drive us to self-initiate, their potential neural underpinnings and the relevance of these models for apathy in patients with HD. The data I present supports the hypothesis that opportunity cost and basal ganglia pathway connectivity may be two important components necessary to generate motivated behaviour and contribute to the development of apathy in HD

Echoes of Vision: Mental Imagery in the Human Brain

When you picture the face of a friend or imagine your dream house, you are using the same parts of your brain that you use to see. How does the same system manage to both accurately analyze the world around it and synthesize visual experiences without any external input at all? We approach this question and others by extending the well-established theory that the human visual system embodies a probabilistic generative model of the visual world. That is, just as visual features co-occur with one another in the real world with a certain probability (the feature “tree” has a high probability of occurring with the feature “green”), so do the patterns of activity that encode those features in the brain. With such a joint probability distribution at its disposal, the brain can not only infer the cause of a given activity pattern on the retina (vision), but can also generate the probable visual consequence of an assumed or remembered cause (imagery). The formulation of this model predicts that the encoding of imagined stimuli in low-level visual areas resemble the encoding of seen stimuli in higher areas. To test this prediction we developed imagery encoding models-a novel tool that reveals how the features of imagined stimuli are encoded in brain activity. We estimated imagery encoding models from brain activity measured while subjects imagined complex visual stimuli, and then compared these to visual encoding models estimated from a matched viewing experiment. Consistent with our proposal, imagery encoding models revealed changes in spatial frequency tuning and receptive field properties that made early visual areas during imagery more functionally similar to higher visual areas during vision. Likewise, signal and noise properties of the voxel activation between vision and imagery favor the generative model interpretation. Our results provide new evidence for an internal generative model of the visual world, while demonstrating that vision is just one of many possible forms of inference that this putative internal model may support

On pattern recognition of brain connectivity in resting-state functional MRI

Dissertação de mestrado integrado em Biomedical Engineering (specialization on Medical Informatics)The human urge and pursuit for information have led to the development of increasingly complex technologies, and new means to study and understand the most advanced and intricate biological system: the human brain. Large-scale neuronal communication within the brain, and how it relates to human behaviour can be inferred by delving into the brain network, and searching for patterns in connectivity. Functional connectivity is a steady characteristic of the brain, and it has been proved to be very useful for examining how mental disorders affect connections within the brain. The detection of abnormal behaviour in brain networks is performed by experts, such as physicians, who limit the process with human subjectivity, and unwittingly introduce errors in the interpretation. The continuous search for alternatives to obtain faster and robuster results have put Machine Learning and Deep Learning in the leading position of computer vision, as they enable the extraction of meaningful patterns, some beyond human perception. The aim of this dissertation is to design and develop an experiment setup to analyse functional connectivity at a voxel level, in order to find functional patterns. For the purpose, a pipeline was outlined to include steps from data download to data analysis, resulting in four methods: Data Download, Data Preprocessing, Dimensionality Reduction, and Analysis. The proposed experiment setup was modeled using as materials resting state fMRI data from two sources: Life and Health Sciences Research Institute (Portugal), and Human Connectome Project (USA). To evaluate its performance, a case study was performed using the In-House data for concerning a smaller number of subjects to study. The pipeline was successful at delivering results, although limitations concerning the memory of the machine used restricted some aspects of this experiment setup’s testing. With appropriate resources, this experiment setup may support the process of analysing and extracting patterns from any resting state functional connectivity data, and aid in the detection of mental disorders.O desejo e a busca intensos do ser humano por informação levaram ao desenvolvimento de tecnologias cada vez mais complexas e novos meios para estudar e entender o sistema biológico mais avançado e intrincado: o cérebro humano. A comunicação neuronal em larga escala no cérebro, e como ela se relaciona com o comportamento humano, pode ser inferida investigando a rede neuronal cerebral e procurando por padrões de conectividade. A conectividade funcional é uma característica constante do cérebro e provou ser muito útil para examinar como os distúrbios mentais afetam as conexões cerebrais. A deteção de anormalidades em imagens de ressonância magnética é realizada por especialistas, como médicos, que limitam o processo com a subjetividade humana e, inadvertidamente, introduzem erros na interpretação. A busca contínua de alternativas para obter resultados mais rápidos e robustos colocou as técnicas de machine learning e deep learning na posição de liderança de visão computacional, pois permitem a extração de padrões significativos e alguns deles para além da percepção humana. O objetivo desta dissertação é projetar e desenvolver uma configuração experimental para analisar a conectividade funcional ao nível do voxel, a fim de encontrar padrões funcionais. Nesse sentido, foi delineado um pipeline para incluir etapas a começar no download de dados até à análise desses mesmos dados, resultando assim em quatro métodos: Download de Dados, Pré-processamento de Dados, Redução de Dimensionalidade e Análise. A configuração experimental proposta foi modelada usando dados de ressonância magnética funcional de resting-state de duas fontes: Instituto de Ciências da Vida e Saúde (Portugal) e Human Connectome Project (EUA). Para avaliar o seu desempenho, foi realizado um estudo de caso usando os dados internos por considerar um número menor de participantes a serem estudados. O pipeline foi bem-sucedido em fornecer resultados, embora limitações relacionadas com a memória da máquina usada tenham restringido alguns aspetos do teste desta configuração experimental. Com recursos apropriados, esta configuração experimental poderá servir de suporte para o processo de análise e extração de padrões de qualquer conjunto de dados de conectividade funcional em resting-state e auxiliar na deteção de transtornos mentais

Optimal Correction of The Slice Timing Problem and Subject Motion Artifacts in fMRI

Functional magnetic resonance imaging (fMRI) is an extremely popular investigative and clinical imaging tool that allows safe and noninvasive study of the functional living brain. Fundamentally, fMRI measures a physiological signal as it changes over time. The manner in which this spatio-temporal signal is acquired can create technical challenges during image reconstruction that must be corrected for if any meaningful information is to be extracted from the data. Two particular challenges that are fundamentally intertwined with each other are temporal misalignment and spatial misalignment. Temporal misalignment is due to the nature of fMRI acquisition protocols themselves: a 3D volume is created by sampling and stacking multiple 2D slices. However, these slices are not acquired simultaneously or sequentially, and therefore will always be temporally misaligned with each other. Spatial misalignment arises when subject motion is present during the scan, resulting in individual volumes being spatially misaligned with each other. Spatial and temporal misalignment are not independent from each other, and their interaction can cause additional artifacts and reconstruction challenges if not addressed properly. The purpose of this thesis is to critically examine the problem of both spatial and temporal misalignment from a signal processing perspective, while considering the physical nature and origin of the signal itself, and develop optimal correction routines for spatial and temporal misalignment and their associated artifacts. One of the most immediate problems associated with temporal misalignment is that the order in which the slices are acquired must be known in order for correction to be possible. Surprisingly, this information is rarely provided with old or shared data, meaning that this critical preprocessing step must be skipped, significantly lowering the value of the data. We use the spatio-temporal properties of the fMRI signal to develop a robust and accurate algorithm to infer the slice acquisition order retrospectively from any fMRI scan. The ability to extract the interleave parameter from any data set allows us to perform slice timing correction even if this information had been lost, or was not provided with the scan. In the next section of this work, we develop a new optimal method of slice timing correction (Filter-Shift) based on the fundamental properties of sampling theory in digital signal processing. By examining the properties of the signal of interest (The blood oxygen level depended signal: BOLD signal), we are able to design and implement an effective FIR filter to simultaneously remove noise and reconstruct the signal of interest at any shifted offset, without the need for sub-optimal interpolation. In the final section, we investigate the effects of different motion types on the MR signal based on the Bloch equation, in order to develop a theoretical foundation from which we can create an optimal correction method. We devise a novel method to remove these artifacts: Discrete reconstruction of irregular fMRI trajectory (DRIFT). Our method calculates the exact displacement of the k-space samples due to motion at each dwell time and retrospectively corrects each slice of the fMRI volume using an inverse nonuniform Fourier transform. We conclude that a hybrid approach with both prospective and retrospective components are essentially required for optimal removal of motion artifacts from the fMRI data. The combined work of this thesis provides two theoretically sound and extremely effective correction routines, that both remove artifacts and restore the underlying sampled signal. Motion correction and slice timing correction are typically the first two preprocessing steps to be applied to any fMRI data, and thus provide the foundation for any further analysis. While many other preprocessing steps can be omitted or included depending on the analysis, motion correction and slice timing correction are unequivocally beneficial and necessary for accurate and reliable results. This work provides a theoretical and quantitative framework that describes the optimal removal of artifacts associated with motion and slice timing

Generative models for group fMRI data

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 151-174).In this thesis, we develop an exploratory framework for design and analysis of fMRI studies. In our framework, the experimenter presents subjects with a broad set of stimuli/tasks relevant to the domain under study. The analysis method then automatically searches for likely patterns of functional specificity in the resulting data. This is in contrast to the traditional confirmatory approaches that require the experimenter to specify a narrow hypothesis a priori and aims to localize areas of the brain whose activation pattern agrees with the hypothesized response. To validate the hypothesis, it is usually assumed that detected areas should appear in consistent anatomical locations across subjects. Our approach relaxes the conventional anatomical consistency constraint to discover networks of functionally homogeneous but anatomically variable areas. Our analysis method relies on generative models that explain fMRI data across the group as collections of brain locations with similar profiles of functional specificity. We refer to each such collection as a functional system and model it as a component of a mixture model for the data. The search for patterns of specificity corresponds to inference on the hidden variables of the model based on the observed fMRI data. We also develop a nonparametric hierarchical Bayesian model for group fMRI data that integrates the mixture model prior over activations with a model for fMRI signals. We apply the algorithms in a study of high level vision where we consider a large space of patterns of category selectivity over 69 distinct images. The analysis successfully discovers previously characterized face, scene, and body selective areas, among a few others, as the most dominant patterns in the data. This finding suggests that our approach can be employed to search for novel patterns of functional specificity in high level perception and cognition.by Danial Lashkari.Ph.D

Shape Processing across Lateral Occipital Cortex

There are two predominant means of identifying visual areas in the human brain; retinotopy (exploiting maps of the visual field) and localisers (exploiting functional selectivity). This thesis aimed to bridge those two approaches, assessing the roles of LO-1 and LO-2; two retinotopically-defined regions that show overlap with the functionally-defined (shape selective) Lateral Occipital Complex (LOC). More generally, we asked what is the nature of the shape representation across Lateral Occipital cortex? We first probed the functional roles of LO-1 and LO-2, finding that LO-2 is the more shape-sensitive region of the pair and will respond to second order shape stimuli, whereas LO-1 may process more local cues (perhaps orientation information). Our later work then assessed neural shape representations across visual cortex, identifying two discrete representations; ‘Shape-profile’ (essentially retinotopic responses) and ‘Shape-complexity’ (responses based upon the complexity of a shape’s contour). The latter dimension captured variance in LOC, and surprisingly LO-2. This indicates that even explicit visual field maps can respond to non‑retinotopic attributes such as curvature complexity. Intriguingly, a transition between dimensions occurred around LO-1 and LO-2. Finally, we explicitly tested whether the ‘Shape-complexity’ representation may be curvature based. Our results implied that radial shape protrusions are highly salient features for Lateral Occipital cortex, but it is not necessarily the points of maximal curvature that are being responded to. Instead, we hypothesise that it is the convergent lines comorbid with curvature that neurons may be attuned to, as such lines likely represent the most salient or characteristic features in a given shape. In sum, we argue for an evolving shape representation across visual cortex, with some degree of shape sensitivity first emerging around LO-1 and LO-2. These maps may then be acting as preliminary processing stages for more selective shape tunings in LOC

Brain Plasticity associated with Predictive Masking and Glaucoma

Glaucoma is a disease resulting from damage at the optic nerve, the “highway” through which visual information travels from the retina towards the visual brain. Such lesion deprives the visual cortex of the regular input, causing interruptions within the visual field – scotoma. However, even when such lesions occur, perception remains stable as the human visual system perceptually masks the insult with the visual features of nearby regions of the visual field. To unravel the neural mechanisms by which this remarkable capacity occurs in glaucomatous individuals, we used functional magnetic resonance imaging (fMRI) and neural modelling to track changes in cortical population receptive fields (pRFs). We found that visual neurons from early visual areas (V1-3) expanded their pRFs both inside and at the vicinity of the lesion. V1 pRFs also shifted their preferred central position towards the outside of the scotoma. By doing so, neural populations were able to process information from spared visual field, consistent with the notion of predictive masking. In contrast, well-sighted observers did not show similar patterns of neural activity in response to the introduction of an artificial scotoma (AS). Our findings provide evidence of enduring cortical reorganization underlying the predictive spatial masking of scotomas in glaucoma, meeting the contemporary view that early visual areas of the adult human brain retain plastic mechanisms. Furthermore, the involvement of the brain suggests that glaucoma pathogenesis goes beyond the eye