Andrew C. James

Testing for Glaucoma with the spatial frequency doubling illusion

We examined the performance of tests for glaucoma based on the spatial frequency doubling (FD) illusion. Contrast thresholds for seeing the FD illusion in four large visual field regions were measured from 340 subjects who were tested up to seven times over 2 years. Median sensitivities of 91% at specificities of 95% were obtained. Test-retest variability for the worst hemifield thresholds averaged 2.22 db +/- 0.09 S.E. for all tested groups, and significant progression was observed for glaucoma suspects over the seven visits, indicating that tests based on the FD illusion can detect diffuse early glaucomatous loss.

Multifocal fMRI mapping of visual cortical areas

The multifocal mapping of electroretinograms and visual evoked potentials has established an important role in both basic research and in diagnostic procedures. We have developed a multifocal mapping method for fMRI, which allows detailed analysis of multiple local visual field representations in the cortex with excellent spatial resolution. Visual field was divided into 60 regions in a dartboard configuration, scaled according to the human magnification factor. Within blocks of 7 s, half of the regions were stimulated with checkerboard patterns contrast reversing at 8 reversals per second, while the other half remained inactive at uniform luminance. The subset of active regions changed with each 7-s block, according to an orthogonal design. Functional MRI was done with a 3-T GE Signa and analyzed with SPM2. A general linear model was fitted producing activation maps for each of the 60 regions, and local signal changes were quantified from V1. These activation maps were next assigned to 3D surface models of the cortical sheet, and then unfolded, using the Brain à la Carte software package. Phase-encoded retinotopic analysis of conventional design served as qualitative comparison data. With multifocal fMRI, all regions were mapped with good signal-to-noise ratio in V1, and subsets of regions showed activation in V2 and V3. This method allows rapid and direct exploration of multiple local visual responses, and is thus able to give complementary information to phase encoded mapping of retinotopic areas.

Evidence for spatial aliasing effects in the Y-like cells of the magnocellular visual pathway

Several lines of evidence are provided indicating that our visual percept can be dominated by spatial aliasing for viewing conditions near those needed to see the spatial frequency doubled illusion. The apparent aliasing effect indicates that the underlying sampling array has a density 15-30% of that of M-cells, in agreement with the known proportion of Y-like M-cells (M(y)-cells). The presence of aliasing indicates, that there is a separate irregular array of M(y)-cells, and that their role is to rapidly convey information on retinal gain control to the brain rather than to act primarily as inputs to image motion computation.

Effect of temporal sparseness and dichoptic presentation on multifocal visual evoked potentials

Multifocal VEP (mfVEP) responses were obtained from 13 normal human subjects for nine test conditions, covering three viewing conditions (dichoptic and left and right monocular), and three different temporal stimulation forms (rapid contrast reversal, rapid pattern pulse presentation, and slow pattern pulse presentation). The rapid contrast reversal stimulus had pseudorandomized reversals of checkerboards in each visual field region at a mean rate of 25 reversals/s, similar to most mfVEP studies to date. The rapid pattern pulse presentation had pseudorandomized presentations of a checkerboard for one frame, interspersed with uniform grey frames, with a mean rate of 25 presentations/s per region per eye. The slow pattern pulse stimulus had six presentations/s per region per eye. Recording time was 5.3 min/condition. For dichoptic presentation slow pattern pulse responses were 4.6 times larger in amplitude than the contrast reversal responses. Binocular suppression was greatest for the contrast reversal stimulus. Consideration of the signal-to-noise ratios indicated that to achieve a given level of reliability, slow pattern pulse stimuli would require half the recording time of contrast reversal stimuli for monocular viewing, and 0.4 times the recording time for dichoptically presented stimuli. About half the responses to the slow pattern pulse stimuli had peak value exceeding five times their estimated standard error. Responses were about 20% smaller in the upper visual field locations. Space-time decomposition showed that responses to slow pattern pulse were more consistent across visual field locations. We conclude that the pattern pulse stimuli, which we term temporally sparse, maintain the visual system in a high contrast gain state. This more than compensates for the smaller number of presentations in the run, and provides signal-to-noise advantages that may be valuable in clinical application.

Sparse multifocal stimuli for the detection of multiple sclerosis

We compared the diagnostic capabilities of contrast reversal and sparse pattern pulse stimulation for dichoptic multifocal visual evoked potentials (mfVEPs) measured in normal subjects and multiple sclerosis (MS) patients. Multifocal responses were obtained from 27 normal subjects and 50 relapsing‐remitting patients, 26 of whom had experienced optic neuritis (ON+). The patient groups were matched for length of disease and number of clinical attacks. Compared with the responses of normal subjects those of MS patients had significantly smaller response amplitudes, lower signal‐to‐noise ratios, more complex response waveforms, and longer response delays. The effects were larger for sparser stimuli. Sensitivities and specificities for the different stimulus types were estimated from receiver operator characteristic (ROC) plots. Bootstrap estimates of the accuracies of the ROCs for the most promising measure, the template delays, indicated the sparsest stimulus would deliver 92% sensitivity at a false‐positive rate of 0%. In contrast, at 92% sensitivity the conventional mfVEP stimulus misdiagnosed more than 20% of the normal population. The results were similar for patients with no history of ON (ON−). In performing well in patients with no history of ON, the sparse mfVEPs seem to measure progressive damage associated with axon and gray matter losses rather than damage associated with a history of serious inflammation. Ann Neurol 2005;57:904–913

Contrast response of temporally sparse dichoptic multifocal visual evoked potentials

Temporally sparse stimuli have been found to produce larger multifocal visual evoked potentials than rapid contrast-reversal stimuli. We compared the contrast-response functions of conventional contrast-reversing (CR) stimuli and three grades of temporally sparse stimuli, examining both the changes in response amplitude and signal-to-noise ratio (SNR). All stimuli were presented dichoptically to normal adult human subjects. One stimulus variant, the slowest pattern pulse, had interleaved monocular and binocular stimuli. Response amplitudes and SNRs were similar for all stimuli at contrast 0.4 but grew faster with increasing contrast for the sparser stimuli. The best sparse stimulus provided an SNR improvement that corresponded to a recording time improvement of 2.6 times relative to that required for contrast reversing stimuli. Multiple regression of log-transformed response metrics characterized the contrast-response functions by fitting power-law relationships. The exponents for the two sparsest stimuli were significantly larger (P < 0.001) than for the CR stimuli, as were the mean response amplitudes and signal-to-noise ratios for these stimuli. The contrast-dependent response enhancement is discussed with respect to the possible influences of rapid retinal contrast gain control, or intracortical and cortico-geniculate feedback.

Dichoptic multifocal pupillography reveals afferent visual field defects in early type 2 diabetes.

PURPOSE Multifocal pupillographic perimetry was used to examine differences in the visual fields of 23 subjects with early type 2 diabetes (T2D) and 23 age- and sex-matched control subjects. METHODS Independent stimuli were delivered to 44 regions of each eye while pupil responses were recorded with infrared cameras. The stimuli were presented in 8 segments of 30 seconds, and both eyes of each subject were tested twice. The direct and consensual responses provided 88 responses per eye. The diagnostic power of the method was then examined by applying receiver operator analysis to the peak regional contraction amplitudes, time to peaks, and linear combinations of those. RESULTS Dichoptic multifocal pupillography provided response amplitudes with a median z-score of 2.63 +/- 0.26 (SE). The diagnostic performance (expressed as areas under ROC plots) of the eight subjects (32 fields) who had had T2D for at least 10 years was 0.87 +/- 0.06 (mean +/- SE) for response amplitude deviations from normative data, rising to 0.95 +/- 0.04 when between-eye symmetry was considered. Mean pupil size did not have diagnostic power. Comparison of direct and consensual response fields indicated that the observed localized field defects were afferent. CONCLUSIONS Reasonable diagnostic power was obtained, especially for the 16 eyes that had had T2D for more than 10 years, inferring that even in the near absence of visible diabetic retinopathy, some retinal damage had been sustained. This result, if confirmed in a wider group, suggests the that the method may be clinically useful in screening for early damage to the retina in T2D diabetes.

Multifocal pupillographic visual field testing in glaucoma

Purpose:  This preliminary study investigated a means of concurrently assessing the visual field defects of both eyes by recording pupillary responses to multifocal stimuli.

Quantitative multifocal fMRI shows active suppression in human V1

Multifocal functional magnetic resonance imaging has recently been introduced as an alternative method for retinotopic mapping, and it enables effective functional localization of multiple regions‐of‐interest in the visual cortex. In this study we characterized interactions in V1 with spatially and temporally identical stimuli presented alone, or as a part of a nine‐region multifocal stimulus. We compared stimuli at different contrasts, collinear and orthogonal orientations and spatial frequencies one octave apart. Results show clear attenuation of BOLD signal from the central region in the multifocal condition. The observed modulation in BOLD signal could be produced either by neural suppression resulting from stimulation of adjacent regions of visual field, or alternatively by hemodynamic saturation or stealing effects in V1. However, we find that attenuation of the central response persists through a range of contrasts, and that its strength varies with relative orientation and spatial frequency of the central and surrounding stimulus regions, indicating active suppression mechanisms of neural origin. Our results also demonstrate that the extent of the signal spreading is commensurate with the extent of the horizontal connections in primate V1. Hum Brain Mapp, 2008.

A Spatiotemporal White Noise Analysis of Photoreceptor Responses to UV and Green Light in the Dragonfly Median Ocellus

Adult dragonflies augment their compound eyes with three simple eyes known as the dorsal ocelli. While the ocellar system is known to mediate stabilizing head reflexes during flight, the ability of the ocellar retina to dynamically resolve the environment is unknown. For the first time, we directly measured the angular sensitivities of the photoreceptors of the dragonfly median (middle) ocellus. We performed a second-order Wiener Kernel analysis of intracellular recordings of light-adapted photoreceptors. These were stimulated with one-dimensional horizontal or vertical patterns of concurrent UV and green light with different contrast levels and at different ambient temperatures. The photoreceptors were found to have anisotropic receptive fields with vertical and horizontal acceptance angles of 15° and 28°, respectively. The first-order (linear) temporal kernels contained significant undershoots whose amplitudes are invariant under changes in the contrast of the stimulus but significantly reduced at higher temperatures. The second-order kernels showed evidence of two distinct nonlinear components: a fast acting self-facilitation, which is dominant in the UV, followed by delayed self- and cross-inhibition of UV and green light responses. No facilitatory interactions between the UV and green light were found, indicating that facilitation of the green and UV responses occurs in isolated compartments. Inhibition between UV and green stimuli was present, indicating that inhibition occurs at a common point in the UV and green response pathways. We present a nonlinear cascade model (NLN) with initial stages consisting of separate UV and green pathways. Each pathway contains a fast facilitating nonlinearity coupled to a linear response. The linear response is described by an extended log-normal model, accounting for the phasic component. The final nonlinearity is composed of self-inhibition in the UV and green pathways and inhibition between these pathways. The model can largely predict the response of the photoreceptors to UV and green light.