Genetic determination and layout rules of visual cortical architecture

The functional architecture of the primary visual cortex is set up by neurons that preferentially respond to visual stimuli with contours of a specific orientation in visual space. In primates and placental carnivores, orientation preference is arranged into continuous and roughly repetitive (iso-) orientation domains. Exceptions are pinwheels that are surrounded by all orientation preferences. The configuration of pinwheels adheres to quantitative species-invariant statistics, the common design. This common design most likely evolved independently at least twice in the course of the past 65 million years, which might indicate a functionally advantageous trait. The possible acquisition of environment-dependent functional traits by genes, the Baldwin effect, makes it conceivable that visual cortical architecture is partially or redundantly encoded by genetic information. In this conception, genetic mechanisms support the emergence of visual cortical architecture or even establish it under unfavorable environments. In this dissertation, I examine the capability of genetic mechanisms for encoding visual cortical architecture and mathematically dissect the pinwheel configuration under measurement noise as well as in different geometries. First, I theoretically explore possible roles of genetic mechanisms in visual cortical development that were previously excluded from theoretical research, mostly because the information capacity of the genome appeared too small to contain a blueprint for wiring up the cortex. For the first time, I provide a biologically plausible scheme for quantitatively encoding functional visual cortical architecture by genetic information that circumvents the alleged information bottleneck. Key ingredients for this mechanism are active transport and trans-neuronal signaling as well as joined dynamics of morphogens and connectome. This theory provides predictions for experimental tests and thus may help to clarify the relative importance of genes and environments on complex human traits. Second, I disentangle the link between orientation domain ensembles and the species-invariant pinwheel statistics of the common design. This examination highlights informative measures of pinwheel configurations for model benchmarking. Third, I mathematically investigate the susceptibility of the pinwheel configuration to measurement noise. The results give rise to an extrapolation method of pinwheel densities to the zero noise limit and provide an approximated analytical expression for confidence regions of pinwheel centers. Thus, the work facilitates high-precision measurements and enhances benchmarking for devising more accurate models of visual cortical development. Finally, I shed light on genuine three-dimensional properties of functional visual cortical architectures. I devise maximum entropy models of three-dimensional functional visual cortical architectures in different geometries. This theory enables the examination of possible evolutionary transitions between different functional architectures for which intermediate organizations might still exist

Task-based fMRI investigation of the newborn brain: sensorimotor development and learning

Human brain development relies upon the interaction between genetic and environmental factors, and the latter plays a critical role during the perinatal period. In this period, neuronal plasticity through experience-dependent activity is enhanced in the sensory systems, and drive the maturation of the brain. While plasticity is essential for maturation, it is also a source of vulnerability as altered early experiences may interact with the normal course of development. This is particularly evident in infants born preterm, who are prematurely exposed to a sensory-rich environment, and at risk or neurodevelopmental disorders. In keeping with the somatosensory system being at a critical period for development during late gestation, sensorimotor disorders, such as cerebral palsy, are more common in preterm compared with full-term born infants. It is therefore important to understand the normal trajectory of sensorimotor development and how this may be moulded by early sensory experiences. It is well acknowledged that the sensorimotor cortex is topographically organised so that different body parts map to a specific location within the cortex and this map is generally referred to as the ``homunculus". Although the somatotopy has been well characterised in the mature brain, it remains unknown when this organisation emerges during development. Animal studies hints that functional cortical maps might emerge across the equivalent period to the third trimester of human gestation, nevertheless there is currently no evidence. Therefore, I first investigated the topography of the preterm somatosensory cortex in a group of newborn infants. In this purpose I used fMRI and automated robotic tools and measured the functional responses to different sensory simulations (delivered to the mouth, wrists and ankles). The results provide evidence that it is possible to identify distinct areas in the somatosensory cortex devoted to different body parts even in the preterm brain supporting the presence of an immature \textit{homunculus}. Next, I wanted to investigate how activity and development in the sensorimotor system are influenced by experience. Experience-dependent plasticity is the basis of learning (e.g. adaptive behaviour), which is observed in newborn infants. Associative learning in particular has been widely investigated in infants, however, the underlining neuronal processes have previously been poorly understood. To study the neural correlates of associative learning in newborn infants, I developed and used a classical conditioning paradigm in combination with robot-assisted fMRI. The results confirm that associative learning can occur even at this early stage of life and with non-aversive stimuli. More importantly, I could observe learning-induced changes in brain activity within the primary sensory cortices, suggesting that such experience can shape cortical circuitry and is likely to influence early brain development.Open Acces

Neural plasticity and the limits of scientific knowledge

Western science claims to provide unique, objective information about the world. This is supported by the observation that peoples across cultures will agree upon a common description of the physical world. Further, the use of scientific instruments and mathematics is claimed to enable the objectification of science. In this work, carried out by reviewing the scientific literature, the above claims are disputed systematically by evaluating the definition of physical reality and the scientific method, showing that empiricism relies ultimately upon the human senses for the evaluation of scientific theories and that measuring instruments cannot replace the human sensory system. Nativist and constructivist theories of human sensory development are reviewed, and it is shown that nativist claims of core conceptual knowledge cannot be supported by the findings in the literature, which shows that perception does not simply arise from a process of maturation. Instead, sensory function requires a long process of learning through interactions with the environment. To more rigorously define physical reality and systematically evaluate the stability of perception, and thus the basis of empiricism, the development of the method of dimension analysis is reviewed. It is shown that this methodology, relied upon for the mathematical analysis of physical quantities, is itself based upon empiricism, and that all of physical reality can be described in terms of the three fundamental dimensions of mass, length and time. Hereafter the sensory modalities that inform us about these three dimensions are systematically evaluated. The following careful analysis of neuronal plasticity in these modalities shows that all the relevant senses acquire from the environment the capacity to apprehend physical reality. It is concluded that physical reality is acquired rather than given innately, and leads to the position that science cannot provide unique results. Rather, those it can provide are sufficient for a particular environmental setting