Plasticity and stability of ther cortical wiring in the human visual system

Abstract

Deciphering the mechanisms of cortical plasticity is an ultimate goal of neuroscience, as harnessing these mechanisms can foster the development of novel treatments for many neurological disorders. Using state-of-the-art brain imaging techniques, the current the-sis describes the organization of the human visual cortex and its scope of plasticity and stability in four different conditions, ranging from intermittent visual dysfunction in (i) migraine to a variety of congenital chiasmal abnormalities in (ii) FHONDA, (iii) chias-mahypoplasia, and (iv) albinism. (i) Migraine attacks are often preceded by visual anomalies known as aura. The under-lying mechanisms of migraine aura are not fully understood, due to the highly challeng-ing task of capturing patients during aura. Using functional magnetic resonance imaging (fMRI) at 3 T, the alterations of the visual cortex were assessed in five patients with migraine during various forms of aura. The blood oxygen level dependent (BOLD) sig-nal was reduced in patients reporting negative symptoms, i.e. scotoma, and increased in patients who experienced positive symptoms such as flickering or flashing lights. Further-more, patients with bilateral visual symptoms had corresponding bihemispherical changes in BOLD response. These findings suggest that different aura symptoms reflect different types of cerebral dysfunction. Due to misrouting of the optic nerves at the optic chiasm, the visual cortex receives large scale abnormal input in congenital chiasmal abnormalities. Strikingly, the visual perception and basic visual functions remain intact, despite the gross anatomical malfor-mation. This renders congenital chiasmal abnormalities as powerful models to uncover the interplay of developmental plasticity in the human visual cortex. In this thesis, the corti-cal organization was investigated in three types of these abnormalities, namely, FHONDA, chiasma hypoplasia and albinism. (ii) FHONDA (foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis) is a rare new entity of congenital chiasmal abnormalities, characterized by abnormal crossing of the temporal retinal fibers to the contralateral hemisphere in the absence of any pigmentation deficits. The population receptive field (pRF) properties of the visual cortex were determined in two affected individuals. Using fMRI at 7 T, two superimposed hemifield representations were observed on the hemisphere contralateral to the stimulated eye with bilateral pRFs, mirrored across the vertical meridian. This direct evidence of abnormal mapping in FHONDA highlights the independence of pigmentation and development of the visual cortex. (iii) The observed superposition of the two hemifield representations prompts the ques-tion, whether the capacity of the visual cortex is limited to two superimposed maps or there are plastic mechanisms available to host more maps. To address this question, the cortical organization in a rare individual with chiasma hypoplasia was determined. Using ultra-high resolution fMRI at 7 T and diffusion-weighted imaging (DWI) at 3 T, three hemiretinal inputs were found to converge onto the left hemisphere. Additionally, fMRI-based pRF mapping of the left V1-V3 revealed three superimposed hemifield repre-sentations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. These find-ings demonstrate that the developmental plasticity in the human visual cortex provides sufficient scope to support the coexistence and functioning of three hemifield maps within one hemisphere. (iv) In albinism, the pathological decussation of the temporal retinal afferents at the optic chiasm leads to superimposed representations of opposing hemifields in the visual cortex. Applying fMRI-based pRF mapping and connective field (CF)-modeling at 3 T, the early visual cortex was investigated in 6 albinotic participants and 4 controls. In albinism, superimposed retinotopic representations of the contra- and ipsilateral visual hemifield were observed on the hemisphere contralateral to the stimulated eye. This was confirmed by the observation of bilateral pRFs during bilateral mapping. Hemifield mapping revealed similar pRF-sizes for both hemifield representations throughout V1 to V3. The typical increase of V1-sampling extent for V3 compared to V2 was absent in the albinotic participants. The similarity of the pRF-sizes for opposing visual hemifield representations highlights the equivalence of the two maps in the early visual cortex. The altered V1-sampling extent in V3 indicates the adaptation of cortico-cortical connections to the abnormal input of the visual cortex. These results thus suggest that conservative developmental mechanisms are complemented by alterations of the extrastriate cortico-cortical connectivity. In conclusion, the findings of the current thesis indicate, on the one hand, a close correspondence of cortical signals and visual symptoms as demonstrated for migraine aura. On the other hand, in congenital chiasmal abnormalities, the interplay of subcortical stability and cortical plasticity appears to provide sufficient scope to preserve basic aspects of visual perception. The present thesis, therefore, provides significant insights into the development and reorganization of the visual system which may influence new therapeutic approaches.