Properties of Visual Field Maps in Health and Disease

The visual world that surrounds us is represented in and processed by multiple topographically organised maps in the human brain. The organising principle underlying these retinotopic maps is also apparent across other sensory modalities and appears highly conserved across species. Moreover, the template for these visual maps is laid down during development, without the need for visual experience. This thesis binds and summarises seven publications describing work to characterise the functional properties of visual maps in the human brain. Initially, we describe TMS and fMRI measurements designed to probe the functional specificity of two spatially distinct but spatially adjacent maps, LO-1 and LO-2. Concurrently I developed software (visualisation tools) for precise dissection of these areas and to more broadly facilitate the visualisation of neuroimaging data. Our experiment revealed a double dissociation in the functional specificity of these areas, with preferential processing of orientation and shape information by LO-1 and LO-2, respectively. We then used fMRI to examine the effect of spatial attention on the responses measured from visual field maps. We showed that attention modulated visual responses by both enhancing attended locations and suppressing unattended locations; these effects were evident in the maps of early visual cortex and subcortical structures including the lateral geniculate and pulvinar nuclei. Finally, we examined the properties of visual field maps in patients with retinal lesions. Although maps can be abnormally organised with certain congenital visual deficits, we asked whether normally developed maps were able to reorganise when input to them is lost later in life, specifically due to central retinal lesions. Our measurements showed no evidence of reorganisation in the maps of patients with macular degeneration: the extent of activity measured in these maps was both highly predictable based on individual retinal lesions and could be reliably simulated in normally sighted individuals

An Orientation Dependent Size Illusion Is Underpinned by Processing in the Extrastriate Visual Area, LO1

We use the simple, but prominent Helmholtz’s squares illusion in which a vertically striped square appears wider than a horizontally striped square of identical physical dimensions to determine whether functional magnetic resonance imaging (fMRI) BOLD responses in V1 underpin illusions of size. We report that these simple stimuli which differ in only one parameter, orientation, to which V1 neurons are highly selective elicited activity in V1 that followed their physical, not perceived size. To further probe the role of V1 in the illusion and investigate plausible extrastriate visual areas responsible for eliciting the Helmholtz squares illusion, we performed a follow-up transcranial magnetic stimulation (TMS) experiment in which we compared perceptual judgments about the aspect ratio of perceptually identical Helmholtz squares when no TMS was applied against selective stimulation of V1, LO1, or LO2. In agreement with fMRI results, we report that TMS of area V1 does not compromise the strength of the illusion. Only stimulation of area LO1, and not LO2, compromised significantly the strength of the illusion, consistent with previous research that LO1 plays a role in the processing of orientation information. These results demonstrate the involvement of a specific extrastriate area in an illusory percept of size

Multivariate Patterns in the Human Object-Processing Pathway Reveal a Shift from Retinotopic to Shape Curvature Representations in Lateral Occipital Areas, LO-1 and LO-2

Representations in early visual areas are organized on the basis of retinotopy, but this organizational principle appears to lose prominence in the extrastriate cortex. Nevertheless, an extrastriate region, such as the shape-selective lateral occipital cortex (LO), must still base its activation on the responses from earlier retinotopic visual areas, implying that a transition from retinotopic to “functional” organizations should exist. We hypothesized that such a transition may lie in LO-1 or LO-2, two visual areas lying between retinotopically defined V3d and functionally defined LO. Using a rapid event-related fMRI paradigm, we measured neural similarity in 12 human participants between pairs of stimuli differing along dimensions of shape exemplar and shape complexity within both retinotopically and functionally defined visual areas. These neural similarity measures were then compared with low-level and more abstract (curvature-based) measures of stimulus similarity. We found that low-level, but not abstract, stimulus measures predicted V1–V3 responses, whereas the converse was true for LO, a double dissociation. Critically, abstract stimulus measures were most predictive of responses within LO-2, akin to LO, whereas both low-level and abstract measures were predictive for responses within LO-1, perhaps indicating a transitional point between those two organizational principles. Similar transitions to abstract representations were not observed in the more ventral stream passing through V4 and VO-1/2. The transition we observed in LO-1 and LO-2 demonstrates that a more “abstracted” representation, typically considered the preserve of “category-selective” extrastriate cortex, can nevertheless emerge in retinotopic regions

A Direct Demonstration of Functional Differences between Subdivisions of Human V5/MT

Two subdivisions of human V5/MT+: one located posteriorly (MT/TO-1) and the other more anteriorly (MST/TO-2) were identified in human participants using functional magnetic resonance imaging on the basis of their representations of the ipsilateral versus contralateral visual field. These subdivisions were then targeted for disruption by the application of repetitive transcranial magnetic stimulation (rTMS). The rTMS was delivered to cortical areas while participants performed direction discrimination tasks involving 3 different types of moving stimuli defined by the translational, radial, or rotational motion of dot patterns. For translational motion, performance was significantly reduced relative to baseline when rTMS was applied to both MT/TO-1 and MST/TO-2. For radial motion, there was a differential effect between MT/TO-1 and MST/TO-2, with only disruption of the latter area affecting performance. The rTMS failed to reveal a complete dissociation between MT/TO-1 and MST/TO-2 in terms of their contribution to the perception of rotational motion. On the basis of these results, MT/TO-1 and MST/TO-2 appear to be functionally distinct subdivisions of hV5/MT+. While both areas appear to be implicated in the processing of translational motion, only the anterior region (MST/TO-2) makes a causal contribution to the perception of radial motion

An enhanced role for right hV5/MT+ in the analysis of motion in the contra- and ipsi-lateral visual hemi-fields

Previous experiments have demonstrated that transcranial magnetic stimulation (TMS) of human V5/MT+, in either the left or right cerebral hemisphere, can induce deficits in visual motion perception in their respective contra- and ipsi-lateral visual hemi-fields. However, motion deficits in the ipsi-lateral hemi-field are greater when TMS is applied to V5/MT + in the right hemisphere relative to the left hemisphere. One possible explanation for this asymmetry might lie in differential stimulation of sub-divisions within V5/MT + across the two hemispheres. V5/MT + has two major sub-divisions; MT/TO-1 and MST/TO-2, the latter area contains neurons with large receptive fields (RFs) that extend up to 15° further into the ipsi-lateral hemi-field than the former. We wanted to examine whether applying TMS to MT/TO-1 and MST/TO-2 separately could explain the previously reported functional asymmetries for ipsi-lateral motion processing in V5/MT + across right and left cerebral hemispheres. MT/TO-1 and MST/TO-2 were identified in seven subjects using fMRI localisers. In psychophysical experiments subjects identified the translational direction (up/down) of coherently moving dots presented in either the left or right visual field whilst repetitive TMS (25 Hz; 70%) was applied synchronously with stimulus presentation. Application of TMS to MT/TO-1 and MST/TO-2 in the right hemisphere affected translational direction discrimination in both contra-lateral and ipsi-lateral visual fields. In contrast, deficits of motion perception following application of TMS to MT/TO-1 and MST/TO-2 in the left hemisphere were restricted to the contra-lateral visual field. This result suggests an enhanced role for the right hemisphere in processing translational motion across the full visual field

On the role of suppression in spatial attention : evidence from negative BOLD in human subcortical and cortical structures

There is clear evidence that spatial attention increases neural responses to attended stimuli in extrastriate visual areas and, to a lesser degree, in earlier visual areas. Other evidence shows that neurons representing unattended locations can also be suppressed. However, the extent to which enhancement and suppression is observed, their stimulus dependence, and the stages of the visual system at which they are expressed remains poorly understood. Using fMRI we set out to characterize both the task and stimulus dependence of neural responses in the lateral geniculate nucleus (LGN), primary visual cortex (V1), and visual motion area (V5) in humans to determine where suppressive and facilitatory effects of spatial attention are expressed. Subjects viewed a lateralized drifting grating stimulus, presented at multiple stimulus contrasts, and performed one of three tasks designed to alter the spatial location of their attention. In retinotopic representations of the stimulus location, we observed increasing attention-dependent facilitation and decreasing dependence on stimulus contrast moving up the visual hierarchy from the LGN to V5. However, in the representations of unattended locations of the LGN and V1, we observed suppression, which was not significantly dependent on the attended stimulus contrast. These suppressive effects were also found in the pulvinar, which has been frequently associated with attention. We provide evidence, therefore, for a spatially selective suppressive mechanism that acts at a subcortical level

Differential processing of the direction and focus of expansion of optic flow stimuli in areas MST and V3A of the human visual cortex

Human neuropsychological and neuroimaging studies have raised the possibility that different attributes of optic flow stimuli, namely radial direction and the position of the focus of expansion (FOE), are processed within separate cortical areas. In the human brain, visual areas V5/MT+ and V3A have been proposed as integral to the analysis of these different attributes of optic flow stimuli. To establish direct causal relationships between neural activity in human (h)V5/MT+ and V3A and the perception of radial motion direction and FOE position, we used transcranial magnetic stimulation (TMS) to disrupt cortical activity in these areas while participants performed behavioral tasks dependent on these different aspects of optic flow stimuli. The cortical regions of interest were identified in seven human participants using standard functional MRI retinotopic mapping techniques and functional localizers. TMS to area V3A was found to disrupt FOE positional judgments but not radial direction discrimination, whereas the application of TMS to an anterior subdivision of hV5/MT+, MST/TO-2 produced the reverse effects, disrupting radial direction discrimination but eliciting no effect on the FOE positional judgment task. This double dissociation demonstrates that FOE position and radial direction of optic flow stimuli are signaled independently by neural activity in areas hV5/MT+ and V3A.NEW & NOTEWORTHY Optic flow constitutes a biologically relevant visual cue as we move through any environment. With the use of neuroimaging and brain-stimulation techniques, this study demonstrates that separate human brain areas are involved in the analysis of the direction of radial motion and the focus of expansion in optic flow. This dissociation reveals the existence of separate processing pathways for the analysis of different attributes of optic flow that are important for the guidance of self-locomotion and object avoidance

Following the status of visual cortex over time in patients with macular degeneration reveals atrophy of visually deprived brain regions

Purpose: Previous research has shown atrophy of visual cortex can occur in retinotopic representations of retinal lesions resulting from eye disease. However, the time course of atrophy cannot be established from these cross-sectional studies, which included patients with long-standing disease of varying severity. Our aim therefore was to measure visual cortical structure over time in participants after onset of unilateral visual loss resulting from age-related macular degeneration (AMD). Methods: Inclusion criteria were onset of acute unilateral neovascular AMD with bilateral dry-AMD based on clinical examination. Therefore, substantial loss of unilateral visual input to cortex was relatively well-defined in time. Changes in cortical anatomy were assessed in the occipital lobe as a whole, and in cortical representations of the lesion and intact retina, the lesion and intact projection zones, respectively. Whole brain, T1-weighted MRI was taken at diagnosis (before anti-angiogenic treatment to stabilise the retina), during the 3-4-month initial treatment period, with a long-term follow-up ~5 (range 3.8 – 6.1 years) years later. Results: Significant cortical atrophy was detected at long-term follow-up only, with a reduction in mean cortical volume across the whole occipital lobe. Importantly, this reduction was explained by cortical thinning of the lesion projection zone, which suggests additional changes to those associated with normal ageing. Over the period of study, anti-angiogenic treatment stabilised visual acuity and central retinal thickness, suggesting that the atrophy detected was most likely governed by long-term decreased visual input. Conclusions: Our results indicate that consequences of eye disease on visual cortex are atrophic and retinotopic. Our work also raises the potential to follow the status of visual cortex in individuals over time to inform on how best to treat patients, particularly with restorative techniques

Assessing functional reorganization in visual cortex with simulated retinal lesions

Macular degeneration (MD) causes central vision loss, removing input to corresponding representations in the primary visual cortex. There is disagreement concerning whether the cortical regions deprived of input can remain responsive, and the source of reported cortical responses is still debated. To simulate MD in controls, normally sighted participants viewed a bright central disk to adapt the retina, creating a transient 'retinal lesion' during a functional MRI experiment. Participants viewed blocks of faces, scrambled faces and uniform grey stimuli, either passively or whilst performing a one-back task. To assess the impact of the simulated lesion, participants repeated the paradigm using a more conventional mean luminance simulated scotoma without adaptation. Our results suggest our attempt to create a more realistic simulation of a lesion did not impact on responses in the representation of the simulated lesion. While most participants showed no evidence of stimulus-driven activation within the lesion representation, a few individuals (22%) exhibited responses similar to a participant with juvenile MD who completed the same paradigm (without adaptation). Reliability analysis showed that responses in the representation of the lesion were generally consistent irrespective of whether positive or negative. We provide some evidence that peripheral visual stimulation can also produce responses in central representations in controls while performing a task. This suggests that the 'signature of reorganization of visual processing', is not found solely in patients with retinal lesions, consistent with the idea that activity may be driven by unmasked top-down feedback

Assessing the structure of the posterior visual pathway in bilateral macular degeneration

Abstract Macular degeneration (MD) embodies a collection of disorders causing a progressive loss of central vision. Cross-sectional MRI studies have revealed structural changes in the grey and white matter in the posterior visual pathway in MD but there remains a need to understand how such changes progress over time. To that end we assessed the posterior pathway, characterising the visual cortex and optic radiations over a ~ 2-year period in MD patients and controls. We performed cross-sectional and longitudinal analysis of the former. Reduced cortical thickness and white matter integrity were observed in patients compared to controls, replicating previous findings. While faster, neither the rate of thinning in visual cortex nor the reduction in white matter integrity during the ~ 2-year period reached significance. We also measured cortical myelin density; cross-sectional data showed this was higher in patients than controls, likely as a result of greater thinning of non-myelinated tissue in patients. However, we also found evidence of a greater rate of loss of myelin density in the occipital pole in the patient group indicating that the posterior visual pathway is at risk in established MD. Taken together, our results revealed a broad decline in grey and white matter in the posterior visual pathway in bilateral MD; cortical thickness and fractional anisotropy show hints of an accelerated rate of loss also, with larger effects emerging in the occipital pole