fMRI with Central Vision Loss: Effects of Fixation Locus and Stimulus Type.

PURPOSE: In patients with central visual field scotomata, a large part of visual cortex is not adequately stimulated. Patients often use a new eccentric fixation area on intact peripheral retina ("preferred retinal locus"-PRL) that functions as a pseudo-fovea. We used functional magnetic resonance imaging (fMRI) to examine whether stimulating this pseudo-fovea leads to increased activation or altered activation patterns in visual cortex in comparison to stimulating a comparable peripheral area in the opposite hemifield (OppPRL). METHODS: Nineteen patients with binocular central scotomata caused by hereditary retinal dystrophies and an age-matched control group were tested. The center of the visual field, PRL, and OppPRL were stimulated with flickering checkerboard stimuli and object pictures during fMRI measurement. RESULTS: Results show that stimulation with pictures of everyday objects led to overall larger BOLD (blood oxygen level dependent) responses in visual cortex compared to that evoked by stimulation with flickering checkerboards. Patients showed this enhancement as early as in V1. When the PRL was directly stimulated with object pictures, the central representation area in early visual cortex was coactivated in the patients but not in the controls. In higher visual areas beyond retinotopic cortex, BOLD responses to stimulation of the PRL with object pictures were significantly enhanced in comparison to stimulation of the OppPRL area. Highly stable eccentric fixation with the PRL was associated with a higher BOLD signal in visual cortex in patients, and this effect was most pronounced in the conditions with object picture stimulation. CONCLUSIONS: The observed results suggest that naturalistic images are more likely to trigger top-down processes that regulate activation in early visual cortex in patients with central vision loss.

Functional and structural brain modifications induced by oculomotor training in patients with age-related macular degeneration.

Patients with age-related macular degeneration (AMD) are reliant on their peripheral visual field. Oculomotor training can help them to find the best area on intact peripheral retina and to efficiently stabilize eccentric fixation. In this study, nine patients with AMD were trained over a period of 6 months using oculomotor training protocols to improve fixation stability. They were followed over an additional period of 6 months, where they completed an auditory memory training as a sham training. In this cross-over design five patients started with the sham training and four with the oculomotor training. Seven healthy age-matched subjects, who did not take part in any training procedure, served as controls. During the 6 months of training the AMD subjects and the control group took part in three functional and structural magnetic resonance imaging (MRI) sessions to assess training-related changes in the brain function and structure. The sham-training phase was accompanied by two more fMRI measurements, resulting in five MRI sessions at intervals of 3 months for all participants. Despite substantial variability in the training effects, on average, AMD patients benefited from the training measurements as indexed by significant improvements in their fixation stability, visual acuity, and reading speed. The patients showed a significant positive correlation between brain activation changes and improvements in fixation stability in the visual cortex during training. These correlations were less pronounced on the long-term after training had ceased. We also found a significant increase in gray and white matter in the posterior cerebellum after training in the patient group. Our results show that functional and structural brain changes can be associated, at least on the short-term, with benefits of oculomotor and/or reading training in patients with central scotomata resulting from AMD.

Neural correlates of visual search in patients with hereditary retinal dystrophies.

In patients with central visual field scotomata a large part of visual cortex is not adequately stimulated. We investigated evidence for possible upregulation in cortical responses in 22 patients (8 females, 14 males; mean age 41.5 years, range 12-65 years) with central visual field loss due to hereditary retinal dystrophies (Stargardt's disease, other forms of hereditary macular dystrophies and cone-rod dystrophy) and compared their results to those of 22 age-matched controls (11 females, 11 males; mean age, 42.4 years, range, 13-70 years). Using functional magnetic resonance imaging (fMRI) we recorded differences in behavioral and BOLD signal distribution in retinotopic mapping and visual search tasks. Patients with an established preferred retinal locus (PRL) exhibited significantly higher activation in early visual cortex during the visual search task, especially on trials when the target stimuli fell in the vicinity of the PRL. Compared with those with less stable fixation, patients with stable eccentric fixation at the PRL exhibited greater performance levels and more brain activation.

Gray matter alterations in visual cortex of patients with loss of central vision due to hereditary retinal dystrophies.

In patients with central visual field scotomata a large part of visual cortex is not adequately stimulated. Over time this lack of input could lead to a reduction of gray matter in the affected cortical areas. We used Voxel Based Morphometry to investigate structural brain changes in patients with central scotomata due to hereditary retinal dystrophies and compared their results to those of normal sighted subjects. Additionally we correlated clinical and demographic characteristics like duration of disease, scotoma size, visual acuity, fixation stability and reading speed to the amount of gray matter in whole brain analyses within the patient group. We found a decrease in gray matter around the lesion projection zone in visual cortex of patients in comparison to controls. Gray matter loss along the posterior and middle portions of the calcarine sulcus is also correlated with scotoma size, indicating that indeed the lack of functional input provokes the gray matter alterations. In whole brain regression analyses within the patient group we found an additional cluster in the right superior and middle frontal gyri, slightly anterior to the frontal eye fields, where gray matter correlated positively with fixation stability. This could be regarded as a consequence of oculomotor learning.