Visual search and eye movements: Studies of perceptual span

In visual search one tries to find the currently relevant item among other, irrelevant items. In the present study, visual search performance for complex objects (characters, faces, computer icons and words) was investigated, and the contribution of different stimulus properties, such as luminance contrast between characters and background, set size, stimulus size, colour contrast, spatial frequency, and stimulus layout were investigated. Subjects were required to search for a target object among distracter objects in two-dimensional stimulus arrays. The outcome measure was threshold search time, that is, the presentation duration of the stimulus array required by the subject to find the target with a certain probability. It reflects the time used for visual processing separated from the time used for decision making and manual reactions. The duration of stimulus presentation was controlled by an adaptive staircase method. The number and duration of eye fixations, saccade amplitude, and perceptual span, i.e., the number of items that can be processed during a single fixation, were measured. It was found that search performance was correlated with the number of fixations needed to find the target. Search time and the number of fixations increased with increasing stimulus set size. On the other hand, several complex objects could be processed during a single fixation, i.e., within the perceptual span. Search time and the number of fixations depended on object type as well as luminance contrast. The size of the perceptual span was smaller for more complex objects, and decreased with decreasing luminance contrast within object type, especially for very low contrasts. In addition, the size and shape of perceptual span explained the changes in search performance for different stimulus layouts in word search. Perceptual span was scale invariant for a 16-fold range of stimulus sizes, i.e., the number of items processed during a single fixation was independent of retinal stimulus size or viewing distance. It is suggested that saccadic visual search consists of both serial (eye movements) and parallel (processing within perceptual span) components, and that the size of the perceptual span may explain the effectiveness of saccadic search in different stimulus conditions. Further, low-level visual factors, such as the anatomical structure of the retina, peripheral stimulus visibility and resolution requirements for the identification of different object types are proposed to constrain the size of the perceptual span, and thus, limit visual search performance. Similar methods were used in a clinical study to characterise the visual search performance and eye movements of neurological patients with chronic solvent-induced encephalopathy (CSE). In addition, the data about the effects of different stimulus properties on visual search in normal subjects were presented as simple practical guidelines, so that the limits of human visual perception could be taken into account in the design of user interfaces.

Dynamics of contour, object and face processing in the human visual cortex

The neural basis of visual perception can be understood only when the sequence of cortical activity underlying successful recognition is known. The early steps in this processing chain, from retina to the primary visual cortex, are highly local, and the perception of more complex shapes requires integration of the local information. In Study I of this thesis, the progression from local to global visual analysis was assessed by recording cortical magnetoencephalographic (MEG) responses to arrays of elements that either did or did not form global contours. The results demonstrated two spatially and temporally distinct stages of processing: The first, emerging 70 ms after stimulus onset around the calcarine sulcus, was sensitive to local features only, whereas the second, starting at 130 ms across the occipital and posterior parietal cortices, reflected the global configuration. To explore the links between cortical activity and visual recognition, Studies II III presented subjects with recognition tasks of varying levels of difficulty. The occipito-temporal responses from 150 ms onwards were closely linked to recognition performance, in contrast to the 100-ms mid-occipital responses. The averaged responses increased gradually as a function of recognition performance, and further analysis (Study III) showed the single response strengths to be graded as well. Study IV addressed the attention dependence of the different processing stages: Occipito-temporal responses peaking around 150 ms depended on the content of the visual field (faces vs. houses), whereas the later and more sustained activity was strongly modulated by the observers attention. Hemodynamic responses paralleled the pattern of the more sustained electrophysiological responses. Study V assessed the temporal processing capacity of the human object recognition system. Above sufficient luminance, contrast and size of the object, the processing speed was not limited by such low-level factors. Taken together, these studies demonstrate several distinct stages in the cortical activation sequence underlying the object recognition chain, reflecting the level of feature integration, difficulty of recognition, and direction of attention.

A Probabilistic Approach to the Primary Visual Cortex

What can the statistical structure of natural images teach us about the human brain? Even though the visual cortex is one of the most studied parts of the brain, surprisingly little is known about how exactly images are processed to leave us with a coherent percept of the world around us, so we can recognize a friend or drive on a crowded street without any effort. By constructing probabilistic models of natural images, the goal of this thesis is to understand the structure of the stimulus that is the raison d etre for the visual system. Following the hypothesis that the optimal processing has to be matched to the structure of that stimulus, we attempt to derive computational principles, features that the visual system should compute, and properties that cells in the visual system should have. Starting from machine learning techniques such as principal component analysis and independent component analysis we construct a variety of sta- tistical models to discover structure in natural images that can be linked to receptive field properties of neurons in primary visual cortex such as simple and complex cells. We show that by representing images with phase invariant, complex cell-like units, a better statistical description of the vi- sual environment is obtained than with linear simple cell units, and that complex cell pooling can be learned by estimating both layers of a two-layer model of natural images. We investigate how a simplified model of the processing in the retina, where adaptation and contrast normalization take place, is connected to the nat- ural stimulus statistics. Analyzing the effect that retinal gain control has on later cortical processing, we propose a novel method to perform gain control in a data-driven way. Finally we show how models like those pre- sented here can be extended to capture whole visual scenes rather than just small image patches. By using a Markov random field approach we can model images of arbitrary size, while still being able to estimate the model parameters from the data.

Functional imaging of peripheral vision and dorsal stream function in the human cerebral cortex

Visual information processing in brain proceeds in both serial and parallel fashion throughout various functionally distinct hierarchically organised cortical areas. Feedforward signals from retina and hierarchically lower cortical levels are the major activators of visual neurons, but top-down and feedback signals from higher level cortical areas have a modulating effect on neural processing. My work concentrates on visual encoding in hierarchically low level cortical visual areas in human brain and examines neural processing especially in cortical representation of visual field periphery. I use magnetoencephalography and functional magnetic resonance imaging to measure neuromagnetic and hemodynamic responses during visual stimulation and oculomotor and cognitive tasks from healthy volunteers. My thesis comprises six publications. Visual cortex forms a great challenge for modeling of neuromagnetic sources. My work shows that a priori information of source locations are needed for modeling of neuromagnetic sources in visual cortex. In addition, my work examines other potential confounding factors in vision studies such as light scatter inside the eye which may result in erroneous responses in cortex outside the representation of stimulated region, and eye movements and attention. I mapped cortical representations of peripheral visual field and identified a putative human homologue of functional area V6 of the macaque in the posterior bank of parieto-occipital sulcus. My work shows that human V6 activates during eye-movements and that it responds to visual motion at short latencies. These findings suggest that human V6, like its monkey homologue, is related to fast processing of visual stimuli and visually guided movements. I demonstrate that peripheral vision is functionally related to eye-movements and connected to rapid stream of functional areas that process visual motion. In addition, my work shows two different forms of top-down modulation of neural processing in the hierachically lowest cortical levels; one that is related to dorsal stream activation and may reflect motor processing or resetting signals that prepare visual cortex for change in the environment and another local signal enhancement at the attended region that reflects local feed-back signal and may perceptionally increase the stimulus saliency.

CNS injury, γ1 laminin, and its KDI peptide

Nisäkkäillä keskushermoston uudistuminen on rajallista. Keskushermostovamman jälkeen aktivoituu monien paranemista edistävien tekijöiden lisäksi myös estäviä tekijöitä. Monella molekyylillä, kuten laminiinilla, on keskushermoston paranemista tehostava vaikutus. Laminiinit ovat myös kehon tyvikalvojen oleellisia rakennuskomponentteja. Keskushermoston laminiinit ovat tärkeitä sikiökehityksen aikana, esimerkiksi hermosäikeiden ohjauksessa. Myöhemmin ne osallistuvat veriaivoesteen ylläpitoon sekä vammojen jälkeiseen kudosreaktioon. Väitöskirjatutkimuksessani olen selvittänyt lamiiniinien, erityisesti γ1 laminiinin ja sen KDI peptidin, ekspressiota keskushermoston vammatilanteissa. Kokeellisessa soluviljelmäasetelmassa, joka simuloi vammautunutta keskushermostoympäristöä, osoitimme että KDI peptidi voimistaa sekä hermosolujen selviytymistä että hermosäikeiden kasvua. Kainihappo on glutamaattianalogi, ja glutamaattitoksisuudella uskotaan olevan tärkeä merkitys keskushermoston eri vamma- ja sairaustilanteissa tapahtuvassa hermosolukuolemassa. Toisessa väitöskirjani osatyössä osoitimme eläinmallissa KDI peptidin suojaavan rotan aivojen hippokampuksen hermosoluja kainihapon aiheuttamalta solutuholta. Elektrofysiologisilla mittauksilla osoitimme kolmannessa osatyössäni, että KDI peptidi estää glutamaattireseptorivirtoja ja suojaa siten glutamaattitoksisuudelta. Aivoveritulpan aiheuttama aivovaurio on yleinen syy aivohalvaukseen. Viimeisessä osatyössäni tutkimme eläinmallissa laminiinien ekspressiota iskemian vaurioittamassa aivokudoksessa. Laminiiniekspression todettiin voimistuvan vaurion jälkeen sekä tyvikalvo- että soluväliainerakenteissa. Vaurion ympärillä havaittiin astrosyyttejä, jotka jo melko aikaisessa vaiheessa vamman jälkeen ekspressoivat γ1 laminiinia ja KDI peptidiä. Tästä voidaan päätellä laminiinien osallistuvan aivoiskeemisen vaurion patofysiologiaan. Yleisesti väitöskirjatyöni kartoitti laminiinien ekspressiota sekä terveessä että vammautuneessa keskushermostossa. Väitöskirjatyöni tukee hypoteesia, jonka mukaan KDI peptidi suojaa keskushermostoa vaurioilta.

Molecular genetics of Usher syndrome -inherited deafness and blindness

Usher syndrome (USH) is an inherited blindness and deafness disorder with variable vestibular dysfunction. The syndrome is divided into three subtypes according to the progression and severity of clinical symptoms. The gene mutated in Usher syndrome type 3 (USH3), clarin 1 (CLRN1), was identified in Finland in 2001 and two mutations were identified in Finnish patients at that time. Prior to this thesis study, the two CLRN1 gene mutations were the only USH mutations identified in Finnish USH patients. To further clarify the Finnish USH mutation spectrum, all nine USH genes were studied. Seven mutations were identified: one was a previously known mutation in CLRN1, four were novel mutations in myosin VIIa (MYO7A) and two were a novel and a previously known mutation in usherin (USH2A). Another aim of this thesis research was to further study the structure and function of the CLRN1 gene, and to clarify the effects of mutations on protein function. The search for new splice variants resulted in the identification of eight novel splice variants in addition to the three splice variants that were already known prior to this study. Studies of the possible promoter regions for these splice variants showed the most active region included the 1000 bases upstream of the translation start site in the first exon of the main three exon splice variant. The 232 aa CLRN1 protein encoded by the main (three-exon) splice variant was transported to the plasma membrane when expressed in cultured cells. Western blot studies suggested that CLRN1 forms dimers and multimers. The CLRN1 mutant proteins studied were retained in the endoplasmic reticulum (ER) and some of the USH3 mutations caused CLRN1 to be unstable. During this study, two novel CLRN1 sequence alterations were identified and their pathogenicity was studied with cell culture protein expression. Previous studies with mice had shown that Clrn1 is expressed in mouse cochlear hair cells and spiral ganglion cells, but the expression profile in mouse retina remained unknown. The Clrn1 knockout mice display cochlear cell disruption/death, but do not have a retinal phenotype. The zebrafish, Danio rerio, clrn1 was found to be expressed in hair cells associated with hearing and balance. Clrn1 expression was also found in the inner nuclear layer (INL), photoreceptor layer and retinal pigment epithelium layer (RPE) of the zebrafish retina. When Clrn1 production was knocked down with injected morpholino oligonucleotides (MO) targeting Clrn1 translation or correct splicing, the zebrafish larvae showed symptoms similar to USH3 patients. These larvae had balance/hearing problems and reduced response to visual stimuli. The knowledge this thesis research has provided about the mutations in USH genes and the Finnish USH mutation spectrum are important in USH patient diagnostics. The extended information about the structure and function of CLRN1 is a step further in exploring USH3 pathogenesis caused by mutated CLRN1 as well as a step in finding a cure for the disease.