Michael B. Hoffmann

Update on the Pattern Electroretinogram in Glaucoma

Purpose. To review the efficacy of the pattern electroretinogram (PERG) in early diagnosis of glaucoma. Methods. Stimulation parameters of check size and temporal frequency are considered. Analyses of various peaks (P50, N95, the N95/P50) and Fourier steady-state are considered. The relation to visual field defects is explored. Results. The PERG is markedly alterated in glaucoma. It shows amplitude reductions in (still) normal areas of the visual field. Optical imaging on the retina needs to be optimal. Higher temporal frequency (>10 reversals/s) improves the sensitivity to detect glaucoma compared with transient stimulation. The ratio between the amplitudes to 0.8° checks and to 16° checks, “PERG ratio,” exploits a check size-specific reduction in early glaucoma and reduces variability. Longitudinal studies suggest that the PERG can indicate incipient glaucoma damage before evidence from the visual field. Conclusions. The PERG is a demanding electrophysiological technique that can serve as a sensitive biomarker for retinal ganglion cell function. With appropriate paradigms, PERG assists in identifying those patients with elevated interocular pressure in whom glaucoma damage is incipient before visual field changes occur.

Directional tuning of human motion adaptation as reflected by the motion VEP

Motion onset evoked visual potentials are dominated by a negativity (N2) at occipital electrodes and a positivity (P2) at the vertex. The degree of true motion processing reflected by N2 and P2 was estimated from the direction specificity of motion adaptation. Adapting stimuli moved to the right and test stimuli (random dot patterns of 26 degrees diameter; 10% contrast; 10.5 degrees /s velocity) moved in one of eight directions, which differed by 45 degrees. VEPs were recorded from occipito/temporal and central sites in eight subjects. Two adaptation effects were observed for N2 (P<0.01): a global amplitude reduction by 47% and a direction-specific reduction by a further 28%. For P2, only the global effect (54%; P<0.01) was observed. The global adaptation effect could also be induced by pattern reversal and pattern-onset adaptation, i.e. stimuli containing ambiguous or very little motion energy, respectively. We conclude that at least 28% of the N2 amplitude reflects the activity of direction-specific elements, whereas P2 does not at all.

Time course of motion adaptation: Motion-onset visual evoked potentials and subjective estimates

The aim of this study was to quantitatively describe the dynamics of adaptation to visual motion with electrophysiological and psychophysical methods in man. We recorded visual evoked potentials (VEPs) to motion onset of random dot patterns from occipital and occipito-temporal electrodes during a succession of adaptation-recovery sequences. In these sequences the test stimulus was used to set the adaptation level: seven trials with 70% motion duty cycle (adaptation) followed by seven trials of 7% motion duty cycle (recovery). In a similar paradigm we determined the length of the perceptual motion after-effect to obtain a psychophysical measure of the time course of motion adaptation. Our results show a highly significant reduction of the N2 amplitude in the maximally compared to the minimally adapted condition (P < 0.001). Electrophysiological and psychophysical results both indicate that adaptation to visual motion is faster than recovery: The data were fit with an exponential model yielding adaptation and recovery time constants, respectively, of 2.5 and 10.2 s for the N2 amplitude (occipito temporal derivation) and of 7.7 and 16.7 s for the perceptual motion after-effect. Implications for the design of motion stimuli are discussed, e.g. a motion stimulus moving 10% of the time may lead to about 30% motion adaptation.

Abnormal retinotopic representations in human visual cortex revealed by fMRI

The representation of the visual field in early visual areas is retinotopic. The point-to-point relationship on the retina is therefore maintained on the convoluted cortical surface. Functional magnetic resonance imaging (fMRI) has been able to demonstrate the retinotopic representation of the visual field in occipital cortex of normal subjects. Furthermore, visual areas that are retinotopic can be identified on computationally flattened cortical maps on the basis of positions of the vertical and horizontal meridians. Here, we investigate abnormal retinotopic representations in human visual cortex with fMRI. We present three case studies in which patients with visual disorders are investigated. We have tested a subject who only possesses operating rod photoreceptors. We find in this case that the cortex undergoes a remapping whereby regions that would normally represent central field locations now map more peripheral positions in the visual field: In a human albino we also find abnormal visual cortical activity. Monocular stimulation of each hemifield resulted in activations in the hemisphere contralateral to the stimulated eye. This is consistent with abnormal decussation at the optic chiasm in albinism. Finally, we report a case where a lesion to white matter has resulted in a lack of measurable activity in occipital cortex. The activity was absent for a small region of the visual field, which was found to correspond to the subjects field defect. The cases selected have been chosen to demonstrate the power of fMRI in identifying abnormalities in the cortical representations of the visual field in patients with visual dysfunction. Furthermore, the experiments are able to show how the cortex is capable of modifying the visual field representation in response to abnormal input.

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.

Retinotopic mapping of the human visual cortex at a magnetic field strength of 7 T

OBJECTIVE fMRI-based retinotopic mapping data obtained at a magnetic field strength of 7T are evaluated and compared to 3T acquisitions. METHODS With established techniques retinotopic mapping data were obtained in four subjects for 25 slices parallel to the calcarine sulcus at 7 and 3T for three voxel sizes (2.5(3), 1.4(3), and 1.1(3)mm(3)) and in two subjects for 49 slices at 7T for 2.5(3)mm(3) voxels. The data were projected to the flattened representation of T1 weighted images acquired at 3T. RESULTS The obtained retinotopic maps allowed for the identification of visual areas in the occipito-parietal cortex. The mean coherence increased with magnetic field strength and with voxel size. At 7T, the occipital cortex could be sampled with high sensitivity in a short single session at high resolution. Alternatively, at lower resolution simultaneous mapping of a great expanse of occipito-parietal cortex was possible. CONCLUSION Retinotopic mapping at 7T aids a detailed description of the visual areas. Here, recent findings of multiple stimulus-driven retinotopic maps along the intraparietal sulcus are supported. SIGNIFICANCE Retinotopic mapping at 7T opens the possibility to detail our understanding of the cortical visual field representations in general and of their plasticity in visual system pathologies.

Abnormal visual projection in a human albino studied with functional magnetic resonance imaging and visual evoked potentials

The albino visual pathway is abnormal in that many fibres from the temporal retina project to the contralateral visual cortex. The visual projections in a human albino and a control have been investigated with fMRI and VEP during independent visual stimulation of both hemifields. Activity in the occipital cortex in the normal was contralateral to the stimulated visual field, whereas it was contralateral to the stimulated eye in the albino, independent of the stimulated visual field. Thus, the albino visual cortex is activated not only by stimulation in the contralateral visual field, but also by abnormal input representing the ipsilateral visual field. These novel findings help elucidate the nature of albino misrouting.

Pattern-onset stimulation boosts central multifocal VEP responses

Multifocal visual evoked potentials (VEP) allow one to assess whether stimulation at specific visual field locations elicits cortical activity; it might therefore enable us to conduct objective visual field perimetry. However, due to the cortical folding, which differs markedly between subjects, a particular electroencephalogram generator may fail to project signal on some recording electrodes. This may lead to false alarms for potential scotomata. Here we compare pattern-reversal and pattern-onset stimulation in their efficacy to activate the visual cortex and recorded mfVEPs to 60 locations comprising a visual field of 44 degrees diameter. We report three main findings: (1) Pattern-onset compared to pattern-reversal enhances the amplitude by 30% for stimulation of the central visual field (<10 degrees radius), while evoking 30% less response in the periphery (>15 degrees ). (2) Although pattern-onset and pattern-reversal responses differ markedly in their eccentricity dependence, they have a similar topographical distribution. (3) By combining both stimuli, the number of false positives was reduced to less than 1.5% of the visual field locations tested. We conclude that pattern-onset and pattern-reversal activate identical visual cortical areas but target different neural mechanisms within these areas. Furthermore, pattern-onset stimulation greatly increases the sensitivity of the mfVEP to assess the cortical representation of the central 10 degrees of the visual field.

Retinal abnormalities in human albinism translate into a reduction of grey matter in the occipital cortex

Albinism is a genetic condition associated with abnormalities of the visual system. Defects in melanin production cause underdevelopment of the fovea, reduced retinal cell numbers and abnormal routing of ganglion cell nerve fibres at the optic chiasm. We examined 19 subjects with albinism and 26 control subjects to determine whether retinal abnormalities affect the structure of the visual cortex. Whole‐brain, high‐resolution anatomical magnetic resonance imaging volumes from each subject were obtained on a 1.5‐T scanner and segmented into grey and white matter. A voxel‐wise statistical comparison of grey and white matter volumes in the occipital lobes between the two groups was performed using voxel‐based morphometry. Our analysis revealed a regionally specific decrease in grey matter volume at the occipital poles in albinism. The location of the decrease in grey matter corresponds to the cortical representation of the central visual field. This reduction is likely to be a direct result of decreased ganglion cell numbers in central retina in albinism.

Pigmentation predicts the shift in the line of decussation in humans with albinism

In albinism a large proportion of nerve fibres originating in temporal retina cross the midline at the chiasm and project to the contralateral hemisphere. Studies in rodents with albinism have suggested that the extent of this misrouting at the chiasm is inversely related to pigmentation levels. Here, we examine whether there is evidence for a similar relationship in humans with albinism. Functional MRI was performed on 18 subjects with albinism, 17 control subjects and six controls with nystagmus as they underwent hemifield visual stimulation of nasal or temporal retina. Functional activation in 16 coronal slices beginning at the posterior occipital lobes were analysed and the extent of hemispheric response lateralization at each slice position was determined. During temporal retina stimulation, the control response was lateralized to the hemisphere ipsilateral to the stimulated eye for all slices. In albinos, the response in posterior slices was predominantly in the contralateral hemisphere, consistent with misrouting of temporal retina fibres. However, as slice location became progressively anterior, response lateralization reverted to the ipsilateral hemisphere. The slice location at which the transition from contra‐ to ipsilateralization occurred provided an estimate of the extent of fibre misrouting in the individual. The slice transition location correlated negatively with pigmentation level, providing the first evidence for a relationship between pigmentation and the extent of misrouting in humans with albinism.