Gaze-contingent flicker pupil perimetry detects scotomas in patients with cerebral visual impairments or glaucoma

The pupillary light reflex is weaker for stimuli presented inside as compared to outside absolute scotomas. Pupillograph perimetry could thus be an objective measure of impaired visual processing. However, the diagnostic accuracy in detecting scotomas has remained unclear. We quantitatively investigated the accuracy of a novel form of pupil perimetry. The new perimetry method, termed gaze-contingent flicker pupil perimetry, consists of the repetitive on, and off flickering of a bright disk (2 hz; 320 cd/m; 4° diameter) on a gray background (160 cd/m) for 4 seconds per stimulus location. The disk evokes continuous pupil oscillations at the same rate as its flicker frequency, and the oscillatory power of the pupil reflects visual sensitivity. We monocularly presented the disk at a total of 80 locations in the central visual field (max. 15°). The location of the flickering disk moved along with gaze to reduce confounds of eye movements (gaze-contingent paradigm). The test lasted ~5 min per eye and was performed on 7 patients with cerebral visual impairment (CVI), 8 patients with primary open angle glaucoma (age >45), and 14 healthy, age/gender-matched controls. For all patients, pupil oscillation power (FFT based response amplitude to flicker) was significantly weaker when the flickering disk was presented in the impaired as compared to the intact visual field (CVI: 12%, AUC = 0.73; glaucoma: 9%, AUC = 0.63). Differences in power values between impaired and intact visual fields of patients were larger than differences in power values at corresponding locations in the visual fields of the healthy control group (CVI: AUC = 0.95; glaucoma: AUC = 0.87). Pupil sensitivity maps highlighted large field scotomas and indicated the type of visual field defect (VFD) as initially diagnosed with standard automated perimetry (SAP) fairly accurately in CVI patients but less accurately in glaucoma patients. We provide the first quantitative and objective evidence of flicker pupil perimetry's potential in detecting CVI-and glaucoma-induced VFDs. Gaze-contingent flicker pupil perimetry is a useful form of objective perimetry and results suggest it can be used to assess large VFDs with young CVI patients whom are unable to perform SAP

Continuous perception of motion and shape across saccadic eye movements

Although our naïve experience of visual perception is that it is smooth and coherent, the actual input from the retina involves brief and discrete fixations separated by saccadic eye movements. This raises the question of whether our impression of stable and continuous vision is merely an illusion. To test this, we examined whether motion perception can “bridge” a saccade in a two-frame apparent motion display in which the two frames were separated by a saccade. We found that transformational apparent motion, in which an object is seen to change shape and even move in three dimensions during the motion trajectory, continues across saccades. Moreover, participants preferred an interpretation of motion in spatial, rather than retinal, coordinates. The strength of the motion percept depended on the temporal delay between the two motion frames and was sufficient to give rise to a motion-from-shape aftereffect, even when the motion was defined by a second-order shape cue (“phantom transformational apparent motion”). These findings suggest that motion and shape information are integrated across saccades into a single, coherent percept of a moving object.Psycholog

Time course of spatiotopic updating across saccades

Humans move their eyes several times per second, yet we perceive the outside world as continuous despite the sudden disruptions created by each eye movement. To date, the mechanism that the brain employs to achieve visual continuity across eye movements remains unclear. While it has been proposed that the oculomotor system quickly updates and informs the visual system about the upcoming eye movement, behavioral studies investigating the time course of this updating suggest the involvement of a slow mechanism, estimated to take more than 500 ms to operate effectively. This is a surprisingly slow estimate, because both the visual system and the oculomotor system process information faster. If spatiotopic updating is indeed this slow, it cannot contribute to perceptual continuity, because it is outside the temporal regime of typical oculomotor behavior. Here, we argue that the behavioral paradigms that have been used previously are suboptimal to measure the speed of spatiotopic updating. In this study, we used a fast gaze-contingent paradigm, using high phi as a continuous stimulus across eye movements. We observed fast spatiotopic updating within 150 ms after stimulus onset. The results suggest the involvement of a fast updating mechanism that predictively influences visual perception after an eye movement. The temporal characteristics of this mechanism are compatible with the rate at which saccadic eye movements are typically observed in natural viewing

Intra-saccadic displacement sensitivity after a lesion to the posterior parietal cortex

Visual perception is introspectively stable and continuous across eye movements. It has been hypothesized that displacements in retinal input caused by eye movements can be dissociated from displacements in the external world using extra-retinal information, such as a corollary discharge from the oculomotor system. The extra-retinal information can inform the visual system about an upcoming eye movement and accompanying displacements in retinal input. The parietal cortex has been hypothesized to be critically involved in integrating retinal and extra-retinal information. Two tasks have been widely used to assess the quality of this integration: double-step saccades and intra-saccadic displacements. Double-step saccades performed by patients with parietal cortex lesions seemed to show hypometric second saccades. However, recently idea has been refuted by demonstrating that patients with very similar lesions were able to perform the double step saccades, albeit taking multiple saccades to reach the saccade target. So, it seems that extra-retinal information is still available for saccade execution after a lesion to the parietal lobe. Here, we investigated whether extra-retinal signals are also available for perceptual judgements in nine patients with strokes affecting the posterior parietal cortex. We assessed perceptual continuity with the intra-saccadic displacement task. We exploited the increased sensitivity when a small temporal blank is introduced after saccade offset (blank effect). The blank effect is thought to reflect the availability of extra-retinal signals for perceptual judgements. Although patients exhibited a relative difference to control subjects, they still demonstrated the blank effect. The data suggest that a lesion to the posterior parietal cortex (PPC) alters the processing of extra-retinal signals but does not abolish their influence altogether

Peri-saccadic orientation identification performance and visual neural sensitivity are higher in the upper visual field

Visual neural processing is distributed among a multitude of sensory and sensory-motor brain areas exhibiting varying degrees of functional specializations and spatial representational anisotropies. Such diversity raises the question of how perceptual performance is determined, at any one moment in time, during natural active visual behavior. Here, exploiting a known dichotomy between the primary visual cortex (V1) and superior colliculus (SC) in representing either the upper or lower visual fields, we asked whether peri-saccadic orientation identification performance is dominated by one or the other spatial anisotropy. Humans (48 participants, 29 females) reported the orientation of peri-saccadic upper visual field stimuli significantly better than lower visual field stimuli, unlike their performance during steady-state gaze fixation, and contrary to expected perceptual superiority in the lower visual field in the absence of saccades. Consistent with this, peri-saccadic superior colliculus visual neural responses in two male rhesus macaque monkeys were also significantly stronger in the upper visual field than in the lower visual field. Thus, peri-saccadic orientation identification performance is more in line with oculomotor, rather than visual, map spatial anisotropies

Point-spread function of the BOLD response across columns and cortical depth in human extra-striate cortex

Columns and layers are fundamental organizational units of the brain. Well known examples of cortical columns are the ocular dominance columns (ODCs) in primary visual cortex and the column-like stripe-based arrangement in the second visual area V2. The spatial scale of columns and layers is beyond the reach of conventional neuroimaging, but the advent of high field magnetic resonance imaging (MRI) scanners (UHF, 7 Tesla and above) has opened the possibility to acquire data at this spatial scale, in-vivo and non-invasively in humans. The most prominent non-invasive technique to measure brain function is blood oxygen level dependent (BOLD) fMRI, measuring brain activity indirectly, via changes in hemodynamics. A key determinant of the ability of high-resolution BOLD fMRI to accurately resolve columns and layers is the point-spread function (PSF) of the BOLD response in relation to the spatial extent of neuronal activity. In this study we take advantage of the stripe-based arrangement present in visual area V2, coupled with sub-millimetre anatomical and gradient-echo BOLD (GE BOLD) acquisition at 7 T to obtain PSF estimates and along cortical depth in human participants. Results show that the BOLD PSF is maximal in the superficial part of the cortex (1.78 mm), and it decreases with increasing cortical depth (0.83 mm close to white matter)

Topographic organization of eye-position dependent gain fields in human visual cortex

The ability to move has introduced animals with the problem of sensory ambiguity: the position of an external stimulus could change over time because the stimulus moved, or because the animal moved its receptors. This ambiguity can be resolved with a change in neural response gain as a function of receptor orientation. Here, we developed an encoding model to capture gain modulation of visual responses in high field (7 T) fMRI data. We characterized population eye-position dependent gain fields (pEGF). The information contained in the pEGFs allowed us to reconstruct eye positions over time across the visual hierarchy. We discovered a systematic distribution of pEGF centers: pEGF centers shift from contra- to ipsilateral following pRF eccentricity. Such a topographical organization suggests that signals beyond pure retinotopy are accessible early in the visual hierarchy, providing the potential to solve sensory ambiguity and optimize sensory processing information for functionally relevant behavior

Cortical depth dependent population receptive field attraction by spatial attention in human V1

Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions

Linear systems analysis for laminar fMRI: evaluating BOLD amplitude scaling for luminance contrast manipulations

A fundamental assumption of nearly all functional magnetic resonance imaging (fMRI) analyses is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal can be described as following linear systems theory. With the advent of ultra-high field (7T and higher) MRI scanners, it has become possible to perform sub-millimeter resolution fMRI in humans. A novel and promising application of sub-millimeter fMRI is measuring responses across cortical depth, i.e. laminar imaging. However, the cortical vasculature and associated directional blood pooling towards the pial surface strongly influence the cortical depth-dependent BOLD signal, particularly for gradient-echo BOLD. This directional pooling may potentially affect BOLD linearity across cortical depth. Here we assess whether the amplitude scaling assumption for linear systems theory holds across cortical depth. For this, we use stimuli with different luminance contrasts to elicit different BOLD response amplitudes. We find that BOLD amplitude across cortical depth scales with luminance contrast, and that this scaling is identical across cortical depth. Although nonlinearities may be present for different stimulus configurations and acquisition protocols, our results suggest that the amplitude scaling assumption for linear systems theory across cortical depth holds for luminance contrast manipulations in sub-millimeter laminar BOLD fMRI

Gaze-Contingent Flicker Pupil Perimetry Detects Scotomas in Patients With Cerebral Visual Impairments or Glaucoma

Background: The pupillary light reflex is weaker for stimuli presented inside as compared to outside absolute scotomas. Pupillograph perimetry could thus be an objective measure of impaired visual processing. However, the diagnostic accuracy in detecting scotomas has remained unclear. We quantitatively investigated the accuracy of a novel form of pupil perimetry.Methods: The new perimetry method, termed gaze-contingent flicker pupil perimetry, consists of the repetitive on, and off flickering of a bright disk (2 hz; 320 cd/m2; 4° diameter) on a gray background (160 cd/m2) for 4 seconds per stimulus location. The disk evokes continuous pupil oscillations at the same rate as its flicker frequency, and the oscillatory power of the pupil reflects visual sensitivity. We monocularly presented the disk at a total of 80 locations in the central visual field (max. 15°). The location of the flickering disk moved along with gaze to reduce confounds of eye movements (gaze-contingent paradigm). The test lasted ~5 min per eye and was performed on 7 patients with cerebral visual impairment (CVI), 8 patients with primary open angle glaucoma (age >45), and 14 healthy, age/gender-matched controls.Results: For all patients, pupil oscillation power (FFT based response amplitude to flicker) was significantly weaker when the flickering disk was presented in the impaired as compared to the intact visual field (CVI: 12%, AUC = 0.73; glaucoma: 9%, AUC = 0.63). Differences in power values between impaired and intact visual fields of patients were larger than differences in power values at corresponding locations in the visual fields of the healthy control group (CVI: AUC = 0.95; glaucoma: AUC = 0.87). Pupil sensitivity maps highlighted large field scotomas and indicated the type of visual field defect (VFD) as initially diagnosed with standard automated perimetry (SAP) fairly accurately in CVI patients but less accurately in glaucoma patients.Conclusions: We provide the first quantitative and objective evidence of flicker pupil perimetry's potential in detecting CVI-and glaucoma-induced VFDs. Gaze-contingent flicker pupil perimetry is a useful form of objective perimetry and results suggest it can be used to assess large VFDs with young CVI patients whom are unable to perform SAP