Impact of chiasma opticum malformations on the organization of the human ventral visual cortex.

Congenital malformations of the optic chiasm, such as enhanced and reduced crossing of the optic nerve fibers, are evident in albinism and achiasma, respectively. In early visual cortex the resulting additional visual input from the ipsilateral visual hemifield is superimposed onto the normal retinotopic representation of the contralateral visual field, which is likely due to conservative geniculo-striate projections. Counterintuitively, this organization in early visual cortex does not have profound consequences on visual function. Here we ask, whether higher stages of visual processing provide a correction to the abnormal representation allowing for largely normal perception. To this end we assessed the organization patterns of early and ventral visual cortex in five albinotic, one achiasmic, and five control participants. In albinism and achiasma the mirror-symmetrical superposition of the ipsilateral and contalateral visual fields was evident not only in early visual cortex, but also in the higher areas of the ventral processing stream. Specifically, in the visual areas VO1/2 and PHC1/2 no differences in the extent, the degree of superposition, and the magnitude of the responses were evident in comparison to the early visual areas. Consequently, the highly atypical organization of the primary visual cortex was propagated downstream to highly specialized processing stages in an undiminished and unchanged manner. This indicates largely unaltered cortico-cortical connections in both types of misrouting, i.e., enhanced and reduced crossing of the optic nerves. It is concluded that main aspects of visual function are preserved despite sizable representation abnormalities in the ventral visual processing stream.

Plasticity and stability of the visual system in human achiasma.

The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.

Optic nerve projections in patients with primary ciliary dyskinesia.

PURPOSE: Recently, it has been suggested that misprojections of the temporal retina to the contralateral hemisphere might not be specific for patients with albinism and might also be associated with the Kartagener syndrome (i.e., with situs inversus totalis in the presence of primary ciliary dyskinesia [PCD]). The authors tested whether such projection abnormalities are associated with PCD and situs inversus. METHODS: In 10 patients with PCD (five with situs inversus totalis) and in 10 age- and sex-matched controls, visual evoked potentials (VEPs) were recorded monocularly, as follows: conventional pattern-onset VEPs (cVEPs) and multifocal VEPs (mfVEPs) for 60 locations constituting a visual field of 44° diameter. cVEPs from 13 albinotic subjects were included as a reference. For each eye, interhemispheric difference potentials were calculated and correlated with each other to assess the lateralization of the responses: positive and negative correlation coefficients indicated lateralizations on same or opposite hemispheres, respectively. Misrouted optic nerves are expected to yield negative interocular correlations. RESULTS: For both cVEPs and mfVEPs, the distribution of the correlation coefficients in the PCD patients yielded largely positive values and did not differ from that of the controls. Consequently, neither large- nor small-scale lateralization abnormalities were observed in PCD. Further, the optic nerve projection did not depend on the presence of situs inversus. CONCLUSIONS: The absence of evidence for projection abnormalities in a cohort of 10 subjects with PCD, five of whom had Kartagener syndrome, underscores that misrouting of the optic nerves is not a common trait of these subjects.

Self-organisation in the human visual system--visuo-motor processing with congenitally abnormal V1 input.

Due to an abnormal projection of the temporal retina the albinotic primary visual cortex receives substantial input from the ipsilateral visual field. To test whether representation abnormalities are also evident in higher tier visual, and in motor and somatosensory cortices, brain activity was measured with fMRI in 14 subjects with albinism performing a visuo-motor task. During central fixation, a blue or red target embedded in a distractor array was presented for 250 ms in the left or right visual hemifield. After a delay, the subjects were prompted to indicate with left or right thumb button presses the target presence in the upper or lower hemifield. The fMRI responses were evaluated for different regions of interest concerned with visual, motor and somatosensory processing and compared to previously acquired data from 14 controls. The following results were obtained: (1) in albinism the hit rates in the visuo-motor task were indistinguishable from normal. (2) In area MT and the intraparietal sulcus there was an indication of abnormal lateralisation patterns. (3) Largely normal lateralisation patterns were evident in motor and somatosensory cortices. It is concluded that in human albinism, the abnormal visual field representation is made available for visuo-motor processing with a motor cortex that comprises an essentially normal lateralisation. Consequently, specific adaptations of the mechanisms mediating visuo-motor integration are required in albinism.

Visuo-motor integration in humans: cortical patterns of response lateralisation and functional connectivity.

PURPOSE: We assessed response and functional connectivity patterns of different parts of the visual and motor cortices during visuo-motor integration with particular focus on the intraparietal sulcus (IPS). METHODS: Brain activity was measured during a visuo-motor task in 14 subjects using event-related fMRI. During central fixation, a blue or red target embedded in an array of grey distractors was presented for 250 ms in either the left or right visual hemifield. After a delay, the subjects were prompted to press the upper or lower response button for targets in the upper and lower hemifield with the left or right thumb for blue and red targets, respectively. The fMRI responses were evaluated for different regions of interests (ROIs), and the functional connectivity of the IPS subregions with these ROIs was quantified. RESULTS: In an anterior IPS region and a region in the anterior premotor cortex, presumably the frontal eye fields (FEF), visually driven responses were dominant contralateral to both visual stimulus and effector. Thus, the anterior IPS combines, in contrast to the posterior IPS and the occipital cortex, response properties of cortex activated by visual input and by motor output. Further, functional connectivity with the motor areas was stronger for the anterior than for the posterior IPS regions. DISCUSSION: Anterior IPS and FEF appear to be of major relevance for relating visual and effector information during visuo-motor integration. Patient studies with the devised paradigm are expected to uncover the impact of pathophysiologies and plasticity on the observed cortical lateralisation patterns.

Multifocal visual evoked potentials reveal normal optic nerve projections in human carriers of oculocutaneous albinism type 1a.

PURPOSE: In albinism, part of the temporal retina projects abnormally to the contralateral hemisphere. A residual misprojection is also evident in feline carriers that are heterozygous for tyrosinase-related albinism. This study was conducted to test whether such residual abnormalities can also be identified in human carriers of oculocutaneous tyrosinase-related albinism (OCA1a). METHODS: In eight carriers heterozygous for OCA1a and in eight age- and sex-matched control subjects, monocular pattern-reversal and -onset multifocal visual evoked potentials (mfVEPs) were recorded at 60 locations comprising a visual field of 44 degrees diameter (VERIS 5.01; EDI, San Mateo, CA). For each eye and each stimulus location, interhemispheric difference potentials were calculated and correlated with each other, to assess the lateralization of the responses: positive and negative correlations indicate lateralizations on the same or opposite hemispheres, respectively. Misrouted optic nerves are expected to yield negative interocular correlations. The analysis also allowed for the assessment of the sensitivity and specificity of the detection of projection abnormalities. RESULTS: No significant differences were obtained for the distributions of the interocular correlation coefficients of controls and carriers. Consequently, no local representation abnormalities were observed in the group of OCA1a carriers. For pattern-reversal and -onset stimulation, an assessment of the control data yielded similar specificity (97.9% and 94.6%) and sensitivity (74.4% and 74.8%) estimates for the detection of projection abnormalities. CONCLUSIONS: The absence of evidence for projection abnormalities in human OCA1a carriers contrasts with the previously reported evidence for abnormalities in cat-carriers of tyrosinase-related albinism. This discrepancy suggests that animal models of albinism may not provide a match to human albinism.