Visual Cortex

The neurosciences have experienced tremendous and wonderful progress in many areas, and the spectrum encompassing the neurosciences is expansive. Suffice it to mention a few classical fields: electrophysiology, genetics, physics, computer sciences, and more recently, social and marketing neurosciences. Of course, this large growth resulted in the production of many books. Perhaps the visual system and the visual cortex were in the vanguard because most animals do not produce their own light and offer thus the invaluable advantage of allowing investigators to conduct experiments in full control of the stimulus. In addition, the fascinating evolution of scientific techniques, the immense productivity of recent research, and the ensuing literature make it virtually impossible to publish in a single volume all worthwhile work accomplished throughout the scientific world. The days when a single individual, as Diderot, could undertake the production of an encyclopedia are gone forever. Indeed most approaches to studying the nervous system are valid and neuroscientists produce an almost astronomical number of interesting data accompanied by extremely worthy hypotheses which in turn generate new ventures in search of brain functions. Yet, it is fully justified to make an encore and to publish a book dedicated to visual cortex and beyond. Many reasons validate a book assembling chapters written by active researchers. Each has the opportunity to bind together data and explore original ideas whose fate will not fall into the hands of uncompromising reviewers of traditional journals. This book focuses on the cerebral cortex with a large emphasis on vision. Yet it offers the reader diverse approaches employed to investigate the brain, for instance, computer simulation, cellular responses, or rivalry between various targets and goal directed actions. This volume thus covers a large spectrum of research even though it is impossible to include all topics in the extremely diverse field of neurosciences

Anthropometric and genetic determinants of cardiac morphology and function

Background Cardiac structure and function result from complex interactions between genetic and environmental factors. Population-based studies have relied on 2-dimensional cardiovascular magnetic resonance as the gold-standard for phenotyping. However, this technique provides limited global metrics and is insensitive to regional or asymmetric changes in left ventricular (LV) morphology. High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) with computational quantitative phenotyping, might improve on traditional CMR by enabling the creation of detailed 3D statistical models of the variation in cardiac phenotypes for use in studies of genetic and/or environmental effects on cardiac form or function. Purpose To determine whether 3D-CMR is applicable at scale, and provides methodological and statistical advantages over conventional imaging for large-scale population studies and to apply 3D-CMR to anthropometric and genetic studies of the heart. Methods 1530 volunteers (54.8% females, 74.7% Caucasian, mean age 41.3±13.0 years) without self-reported cardiovascular disease were recruited prospectively to the Digital Heart Project. Using a cardiac atlas-based software, these images were computationally processed and quantitatively analysed. Parameters such as myocardial shape, curvature, wall thickness, relative wall thickness, end-systolic wall stress, fractional wall thickening and ventricular volumes were extracted at over 46,000 points in the model. The relationships between these parameters and systolic blood pressure (SBP), fat mass, lean mass and genetic variationswere analysed using 3D regression models adjusted for body surface area, gender, race, age and multiple testing. Targeted resequencing of titin (TTN), the largest human gene and the commonest genetic cause of dilated cardiomyopathy, was performed in 928 subjects while common variants (~700.000) were genotyped in 1346 subjects. Results Automatically segmented 3D images were more accurate than 2D images at defining cardiac surfaces, resulting in fewer subjects being required to detect a statistically significant 1 mm difference in wall thickness. 3D-CMR enabled the detection of a strong and distinct regionality of the effects of SBP, body composition and genetic variation on the heart. It shows that the precursors of the hypertensive heart phenotype can be traced to healthy normotensives and that different ratios of body composition are associated with particular gender-specific patterns of cardiac remodelling. In 17 asymptomatic subjects with genetic variations associated with dilated cardiomyopathy, early stages of ventricular impairment and wall thinning were identified, which were not apparent by 2D imaging. Conclusions 3D-CMR combined with computational modelling provides high-resolution insight into the earliest stages of heart disease. These methods show promise for population-based studies of the anthropometric, environmental and genetic determinants of LV form and function in health and disease.Open Acces

The integration of bottom-up and top-down signals in human perception in health and disease

To extract a meaningful visual experience from the information falling on the retina, the visual system must integrate signals from multiple levels. Bottom-up signals provide input relating to local features while top-down signals provide contextual feedback and reflect internal states of the organism. In this thesis I will explore the nature and neural basis of this integration in two key areas. I will examine perceptual filling-in of artificial scotomas to investigate the bottom-up signals causing changes in perception when filling-in takes place. I will then examine how this perceptual filling-in is modified by top-down signals reflecting attention and working memory. I will also investigate hemianopic completion, an unusual form of filling-in, which may reflect a breakdown in top-down feedback from higher visual areas. The second part of the thesis will explore a different form of top-down control of visual processing. While the effects of cognitive mechanisms such as attention on visual processing are well-characterised, other types of top-down signal such as reward outcome are less well explored. I will therefore study whether signals relating to reward can influence visual processing. To address these questions, I will employ a range of methodologies including functional MRI, magnetoencephalography and behavioural testing in healthy participants and patients with cortical damage. I will demonstrate that perceptual filling-in of artificial scotomas is largely a bottom-up process but that higher cognitive functions can modulate the phenomenon. I will also show that reward modulates activity in higher visual areas in the absence of concurrent visual stimulation and that receiving reward leads to enhanced activity in primary visual cortex on the next trial. These findings reveal that integration occurs across multiple levels even for processes rooted in early retinotopic regions, and that higher cognitive processes such as reward can influence the earliest stages of cortical visual processing

Low-level visual processing and its relation to neurological disease

Retinal neurons extract changes in image intensity across space, time, and wavelength. Retinal signal is transmitted to the early visual cortex, where the processing of low-level visual information occurs. The fundamental nature of these early visual pathways means that they are often compromised by neurological disease. This thesis had two aims. First, it aimed to investigate changes in visual processing in response to Parkinson’s disease (PD) by using electrophysiological recordings from animal models. Second, it aimed to use functional magnetic resonance imaging (fMRI) to investigate how low-level visual processes are represented in healthy human visual cortex, focusing on two pathways often compromised in disease; the magnocellular pathway and chromatic S-cone pathway. First, we identified a pathological mechanism of excitotoxicity in the visual system of Drosophila PD models. Next, we found that we could apply machine learning classifiers to multivariate visual response profiles recorded from the eye and brain of Drosophila and rodent PD models to accurately classify these animals into their correct class. Using fMRI and psychophysics, found that measurements of temporal contrast sensitivity differ as a function of visual space, with peripherally tuned voxels in early visual areas showing increased contrast sensitivity at a high temporal frequency. Finally, we used 7T fMRI to investigate systematic differences in achromatic and S-cone population receptive field (pRF) size estimates in the visual cortex of healthy humans. Unfortunately, we could not replicate the fundamental effect of pRF size increasing with eccentricity, indicating complications with our data and stimulus

Biomimetic Radical Chemistry and Applications

The enormous importance of free radical chemistry for a variety of biological events, including ageing and inflammation, has attracted a strong interest in understanding the related mechanistic steps at the molecular level. Modelling the free radical chemical reactivity of biological systems is an important research area. When studying free-radical-based chemical mechanisms, biomimetic chemistry and the design of established biomimetic models come into play to perform experiments in a controlled environment that is suitably designed to be in strict connection with cellular conditions. This Special Issue gives the reader a wide overview of biomimetic radical chemistry, where molecular mechanisms have been defined and molecular libraries of products are developed to also be used as traces for the discovery of some relevant biological processes. Several subjects are presented, with 12 articles and 6 reviews written by specialists in the fields of DNA, proteins, lipids, biotechnological applications, and bioinspired synthesis, having “free radicals” as a common denominator

Investigating the function of the ventral visual reading pathway and its involvement in acquired reading disorders

This thesis investigated the role of the left ventral occipitotemporal (vOT) cortex and how damage to this area causes peripheral reading disorders. Functional magnetic resonance imaging (fMRI) studies in volunteers demonstrated that the left vOT is activated by written words over numbers or perceptually-matched baselines, irrespective of the word’s location on the visual field. Mixed results were observed for the comparison of words versus false font stimuli. This response profile suggests that the left vOT is preferentially activated by words or word-like stimuli, due to either: (1) bottom-up specialisation for processing familiar word-forms; (2) top-down task-dependent modulation, or (3) a combination of the two. Further studies are proposed to discriminate between these possibilities. Thirteen patients with left occipitotemporal damage participated in the rehabilitation and fMRI studies. The patients were impaired on word, text and letter reading. A structural analysis showed that damage to the left occipitotemporal white matter, in the vicinity of the inferior longitudinal fasciculus, was associated with slow word reading speed. The fMRI study showed that the patients had reduced activation of the bilateral posterior superior temporal sulci relative to controls. Activity in this area correlated with reading speed. The efficacy of intensive whole-word recognition training was tested. Immediately after the training, trained words were read faster than untrained words, but the effects did not persist until the follow-up assessment. Hence, damage to the left vOT white matter impairs rapid whole-word recognition and is resistant to rehabilitation. The final study investigated the role of spatial frequency (SF) in the lateralisation of vOT function. Lateralisation of high and low SF processing was demonstrated, concordant with the lateralisation for words and faces to the left and right vOT respectively. A perceptual basis for the organisation of vOT cortex might explain why left vOT damage is resistant to treatment

The role of the transcription factor JAGGED in early floral organogenesis

Initiation of organ primordia from pools of undifferentiated cells requires coordinated cytoplasmic growth, oriented cell wall extension, and cell cycle progression. It is debated which of these processes are primary drivers for organ morphogenesis and directly targeted by developmental regulators. The single zinc finger transcription factor JAGGED (JAG) is a direct target of several floral organ identity genes and is expressed in early organ primordia (Dinneny et al., 2004; Ohno et al., 2004; Gomez et al., 2005; Kaufmann et al., 2009). Loss of function jag mutants have narrow floral organs with reduced distal growth. Quantitative 3D imaging has revealed that JAG is required for the transition from meristematic to organ primordium cell behaviour. The transition involves an increase in the rates of cell division and cell growth, a shift from isotropic to anisotropic growth, and modifications in cell size homeostasis in primordia (Schiessl et al., 2012). In this project, ChIP-Seq was combined with transcriptome analysis to identify global direct target genes of JAG. Consistent with the roles of JAG during organ initiation and organ growth, I found that JAG directly repressed genes involved in meristem development, such as the TALE PROTEIN BELL1 and genes involved in organ boundaries specification such as PETAL LOSS. In addition, JAG directly regulated genes involved in growth regulatory pathways, tissue polarity, cell wall modification, and cell cycle progression. For example, JAG directly repressed the cell cycle inhibitors KIP RELATED PROTEIN 2 and 4 (KRP2/4). The krp2 and krp4 mutations suppressed jag loss of function defects in organ growth and cell type patterning. In particular, loss of KRP4 rescued the defects of cell size homeostasis in the primordia of the jag loss of function mutant. In summary, this work revealed that JAG directly coordinates organ patterning with cellular processes required for tissue growth

Assessment and optimisation of 3D optical topography for brain imaging

Optical topography has recently evolved into a widespread research tool for non-invasively mapping blood flow and oxygenation changes in the adult and infant cortex. The work described in this thesis has focused on assessing the potential and limitations of this imaging technique, and developing means of obtaining images which are less artefactual and more quantitatively accurate. Due to the diffusive nature of biological tissue, the image reconstruction is an ill-posed problem, and typically under-determined, due to the limited number of optodes (sources and detectors). The problem must be regularised in order to provide meaningful solutions, and requires a regularisation parameter (\lambda), which has a large influence on the image quality. This work has focused on three-dimensional (3D) linear reconstruction using zero-order Tikhonov regularisation and analysis of different methods to select the regularisation parameter. The methods are summarised and applied to simulated data (deblurring problem) and experimental data obtained with the University College London (UCL) optical topography system. This thesis explores means of optimising the reconstruction algorithm to increase imaging performance by using spatially variant regularisation. The sensitivity and quantitative accuracy of the method is investigated using measurements on tissue-equivalent phantoms. Our optical topography system is based on continuous-wave (CW) measurements, and conventional image reconstruction methods cannot provide unique solutions, i.e., cannot separate tissue absorption and scattering simultaneously. Improved separation between absorption and scattering and between the contributions of different chromophores can be obtained by using multispectral image reconstruction. A method is proposed to select the optimal wavelength for optical topography based on the multispectral method that involves determining which wavelengths have overlapping sensitivities. Finally, we assess and validate the new three-dimensional imaging tools using in vivo measurements of evoked response in the infant brain