Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

A reevaluation of achromatic spatio-temporal vision: nonoriented filters are monocular, they adapt, and can be used for decision making at high flicker speeds

Masking, adaptation, and summation paradigms have been used to investigate the characteristics of early spatio-temporal vision. Each has been taken to provide evidence for (i) oriented and (ii) nonoriented spatial-filtering mechanisms. However, subsequent findings suggest that the evidence for nonoriented mechanisms has been misinterpreted: those experiments might have revealed the characteristics of suppression (eg, gain control), not excitation, or merely the isotropic subunits of the oriented detecting mechanisms. To shed light on this, we used all three paradigms to focus on the ‘high-speed’ corner of spatio-temporal vision (low spatial frequency, high temporal frequency), where cross-oriented achromatic effects are greatest. We used flickering Gabor patches as targets and a 2IFC procedure for monocular, binocular, and dichoptic stimulus presentations. To account for our results, we devised a simple model involving an isotropic monocular filter-stage feeding orientation-tuned binocular filters. Both filter stages are adaptable, and their outputs are available to the decision stage following nonlinear contrast transduction. However, the monocular isotropic filters (i) adapt only to high-speed stimuli—consistent with a magnocellular subcortical substrate—and (ii) benefit decision making only for high-speed stimuli (ie, isotropic monocular outputs are available only for high-speed stimuli). According to this model, the visual processes revealed by masking, adaptation, and summation are related but not identical.

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms

Background - Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. Methods - We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age = 36.9; 11 females) and 20 schizophrenia patients (age = 39.9; 8 females) in an fMRI study. Results - In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster) < 0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster) < 0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster) < 0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. Conclusions - Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas.

The impact of visual-verbal relationships on native-nonnative english speakers' reading processes and comprehension

The aim of this study was to comparatively investigate the impact of visual-verbal relationships that exist in expository texts on the reading process and comprehension of readers from different language background: native speakers of English (LI) and speakers of English as a foreign language (EFL). The study focussed, in this respect, on the visual elements (VEs) mainly graphs and tables that accompanied the selected texts. Two major experiments were undertaken. The first, was for the reading process using the post-reading questionnaire technique. Participants were 163 adult readers representing three groups: 77 (LI), 56 (EFL postgraduates); and 30 (EFL undergraduates). The second experiment was for the reading comprehension using cloze procedure. Participants were 123 representing the same above gorups: 50, 33 and 40 respectively. It was hypothesised that the LI readers would make use of VEs in the reading process in ways different from both EFL groups and that use would enhance each group's comprehension in different aspects and to different levels. In the analysis of the data of both experiments two statistical measurements were used. The chi-square was used to measure the differences between frequencies and the t-test was used to measure the differences between means. The results indicated a significant relationship between readers' language background and the impact of visual-verbal relationships on their reading processes and comprehension of such type of texts. The results also revealed considerable similarities between the two EFL groups in the reading process of texts accompanied by VEs. In the reading comprehension, however, the EFL undergraduates seemed to benefit from the visual-verbal relationships in their comprehension more than the postgraduates, suggesting a weak relationship of this impact for older EFL readers. Furthermore, the results showed considerable similarities between the reading process of texts accompanied by VEs and of whole prose texts. Finally an evaluation of this study was undertaken as well as practical implications for EFL readers and suggestions for future research.

Retrieval of implicit inhibitory processes:the impact of visual field, object-identity, and memory dynamics

After exogenously cueing attention to a peripheral location, the return of attention and response to the location can be inhibited. We demonstrate that these inhibitory mechanisms of attention can be associated with objects and can be automatically and implicitly retrieved over relatively long periods. Furthermore, we also show that when face stimuli are associated with inhibition, the effect is more robust for faces presented in the left visual field. This effect can be even more spatially specific, where most robust inhibition is obtained for faces presented in the upper as compared to the lower visual field. Finally, it is revealed that the inhibition is associated with an object’s identity, as inhibition moves with an object to a new location; and that the retrieved inhibition is only transiently present after retrieval.

The impact of ageing and gender on visual mental imagery processes:a study of performance on tasks from the Complete Visual Mental Imagery Battery (CVMIB)

In this study we aim to evaluate the impact of ageing and gender on different visual mental imagery processes. Two hundred and fifty-one participants (130 women and 121 men; age range = 18–77 years) were given an extensive neuropsychological battery including tasks probing the generation, maintenance, inspection, and transformation of visual mental images (Complete Visual Mental Imagery Battery, CVMIB). Our results show that all mental imagery processes with the exception of the maintenance are affected by ageing, suggesting that other deficits, such as working memory deficits, could account for this effect. However, the analysis of the transformation process, investigated in terms of mental rotation and mental folding skills, shows a steeper decline in mental rotation, suggesting that age could affect rigid transformations of objects and spare non-rigid transformations. Our study also adds to previous ones in showing gender differences favoring men across the lifespan in the transformation process, and, interestingly, it shows a steeper decline in men than in women in inspecting mental images, which could partially account for the mixed results about the effect of ageing on this specific process. We also discuss the possibility to introduce the CVMIB in clinical assessment in the context of theoretical models of mental imagery.

Stimuli of varying spatial scale induce gamma activity with distinct temporal characteristics in human visual cortex

Gamma activity to stationary grating stimuli was studied non-invasively using MEG recordings in humans. Using a spatial filtering technique, we localized gamma activity to primary visual cortex. We tested the hypothesis that spatial frequency properties of visual stimuli may be related to the temporal frequency characteristics of the associated cortical responses. We devised a method to assess temporal frequency differences between stimulus-related responses that typically exhibit complex spectral shapes. We applied this methodology to either single-trial (induced) or time-averaged (evoked) responses in four frequency ranges (0-40, 20-60, 40-80 and 60-100 Hz) and two time windows (either the entire duration of stimulus presentation or the first second following stimulus onset). Our results suggest that stimuli of varying spatial frequency induce responses that exhibit significantly different temporal frequency characteristics. These effects were particularly accentuated for induced responses in the classical gamma frequency band (20-60 Hz) analyzed over the entire duration of stimulus presentation. Strikingly, examining the first second of the responses following stimulus onset resulted in significant loss in stimulus specificity, suggesting that late signal components contain functionally relevant information. These findings advocate a functional role of gamma activity in sensory representation. We suggest that stimulus specific frequency characteristics of MEG signals can be mapped to processes of neuronal synchronization within the framework of coupled dynamical systems.

Subtractive and divisive adaptation in visual motion computations

Models of visual motion processing that introduce priors for low speed through Bayesian computations are sometimes treated with scepticism by empirical researchers because of the convenient way in which parameters of the Bayesian priors have been chosen. Using the effects of motion adaptation on motion perception to illustrate, we show that the Bayesian prior, far from being convenient, may be estimated on-line and therefore represents a useful tool by which visual motion processes may be optimized in order to extract the motion signals commonly encountered in every day experience. The prescription for optimization, when combined with system constraints on the transmission of visual information, may lead to an exaggeration of perceptual bias through the process of adaptation. Our approach extends the Bayesian model of visual motion proposed byWeiss et al. [Weiss Y., Simoncelli, E., & Adelson, E. (2002). Motion illusions as optimal perception Nature Neuroscience, 5:598-604.], in suggesting that perceptual bias reflects a compromise taken by a rational system in the face of uncertain signals and system constraints. © 2007.

Attentional processes link perception and action

Behavioural studies on normal and brain-damaged individuals provide convincing evidence that the perception of objects results in the generation of both visual and motor signals in the brain, irrespective of whether or not there is an intention to act upon the object. In this paper we sought to determine the basis of the motor signals generated by visual objects. By examining how the properties of an object affect an observer's reaction time for judging its orientation, we provide evidence to indicate that directed visual attention is responsible for the automatic generation of motor signals associated with the spatial characteristics of perceived objects.

Cascaded Bayesian processes: an account of bias in orientation perception

Following adaptation to an oriented (1-d) signal in central vision, the orientation of subsequently viewed test signals may appear repelled away from or attracted towards the adapting orientation. Small angular differences between the adaptor and test yield 'repulsive' shifts, while large angular differences yield 'attractive' shifts. In peripheral vision, however, both small and large angular differences yield repulsive shifts. To account for these tilt after-effects (TAEs), a cascaded model of orientation estimation that is optimized using hierarchical Bayesian methods is proposed. The model accounts for orientation bias through adaptation-induced losses in information that arise because of signal uncertainties and neural constraints placed upon the propagation of visual information. Repulsive (direct) TAEs arise at early stages of visual processing from adaptation of orientation-selective units with peak sensitivity at the orientation of the adaptor (theta). Attractive (indirect) TAEs result from adaptation of second-stage units with peak sensitivity at theta and theta+90 degrees , which arise from an efficient stage of linear compression that pools across the responses of the first-stage orientation-selective units. A spatial orientation vector is estimated from the transformed oriented unit responses. The change from attractive to repulsive TAEs in peripheral vision can be explained by the differing harmonic biases resulting from constraints on signal power (in central vision) versus signal uncertainties in orientation (in peripheral vision). The proposed model is consistent with recent work by computational neuroscientists in supposing that visual bias reflects the adjustment of a rational system in the light of uncertain signals and system constraints.

Synchronization processes in nonlinear systems and their relation to cortical oscillatory dynamics

This thesis was focused on theoretical models of synchronization to cortical dynamics as measured by magnetoencephalography (MEG). Dynamical systems theory was used in both identifying relevant variables for brain coordination and also in devising methods for their quantification. We presented a method for studying interactions of linear and chaotic neuronal sources using MEG beamforming techniques. We showed that such sources can be accurately reconstructed in terms of their location, temporal dynamics and possible interactions. Synchronization in low-dimensional nonlinear systems was studied to explore specific correlates of functional integration and segregation. In the case of interacting dissimilar systems, relevant coordination phenomena involved generalized and phase synchronization, which were often intermittent. Spatially-extended systems were then studied. For locally-coupled dissimilar systems, as in the case of cortical columns, clustering behaviour occurred. Synchronized clusters emerged at different frequencies and their boundaries were marked through oscillation death. The macroscopic mean field revealed sharp spectral peaks at the frequencies of the clusters and broader spectral drops at their boundaries. These results question existing models of Event Related Synchronization and Desynchronization. We re-examined the concept of the steady-state evoked response following an AM stimulus. We showed that very little variability in the AM following response could be accounted by system noise. We presented a methodology for detecting local and global nonlinear interactions from MEG data in order to account for residual variability. We found crosshemispheric nonlinear interactions of ongoing cortical rhythms concurrent with the stimulus and interactions of these rhythms with the following AM responses. Finally, we hypothesized that holistic spatial stimuli would be accompanied by the emergence of clusters in primary visual cortex resulting in frequency-specific MEG oscillations. Indeed, we found different frequency distributions in induced gamma oscillations for different spatial stimuli, which was suggestive of temporal coding of these spatial stimuli. Further, we addressed the bursting character of these oscillations, which was suggestive of intermittent nonlinear dynamics. However, we did not observe the characteristic-3/2 power-law scaling in the distribution of interburst intervals. Further, this distribution was only seldom significantly different to the one obtained in surrogate data, where nonlinear structure was destroyed. In conclusion, the work presented in this thesis suggests that advances in dynamical systems theory in conjunction with developments in magnetoencephalography may facilitate a mapping between levels of description int he brain. this may potentially represent a major advancement in neuroscience.

Functional neuroimaging and behavioural studies on global form processing in the human visual system

Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. Behavioural studies using Glass patterns examined sensitivity for detecting radial, rotational and horizontal structure. Neuroimaging experiments using either Glass patterns or arrays of Gabor patches determined the spatio-temporal neural responseto global form. MEG data were analysed using synthetic aperture magnetometry (SAM) to spatially map event-related cortical oscillatory power changes: the temporal sequencing of activity within a discrete cortical area was determined using a Morlet wavelet transform. A case study was conducted to determine the effects of strbismic amblyopia on global form processing: all other observers were normally-sighted. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.

Abnormal visual habituation in pediatric photosensitive epilepsy

Objective - To investigate visual habituation – a measure of visual cortical excitability – in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. Methods - We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75–P100 and P100–N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75–P100 and P100–N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75–P100 and P100–N145 latencies was also analyzed. Results - Statistical analysis revealed significant differences between the three groups in the slope index of N75–P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. Conclusions - Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. Significance This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.