A avaliação da variabilidade inter-individual da atividade funcional é de grande importância na utilização da ressonância magnética funcional (fMRI) no contexto clínico. O objetivo principal desse estudo é analisar a variabilidade da ativação cerebral dos sistemas vestibular e oculomotor, através da fMRI em resposta à estimulação optocinética horizontal e aos movimentos de rastreio e sacade dos olhos. Para isso, imagens por ressonância magnética foram obtidas de vinte e três voluntários assintomáticos (treze para o estudo optocinético e dez para os estudos rastreio e sacade) em um scanner de 1.5 T Siemens (Magneton Vision) com seqüências do tipo EPI-BOLD. Os mapas estatísticos foram obtidos no programa Brain Voyager, utilizando o método Modelo Geral Linear. Encontramos ativação significante no córtex visual primário, ao longo do giro occipital médio e inferior, no giro temporal médio, superior e inferior, no giro pós- e pré-central, ao longo do giro frontal inferior, superior e médio, no giro supramarginal, no lobo parietal superior e inferior, na ínsula e no cíngulo anterior e posterior. Grupos de atividade também foram encontrados em estruturas subcorticais (putamen, globo pálido, corpo caloso e tálamo), além do cerebelo. A análise da freqüência de ativação revelou uma alta variabilidade entre voluntários. Contudo, as regiões com maior freqüência de ativação foram as áreas frontais e a área que compreende o giro temporal médio e médio superior. Utilizamos dois métodos para a análise dos índices de lateralização, o primeiro admite um valor estatístico fixo e o segundo leva em consideração a dependência do limiar estatístico com o número de pixels ativados, o segundo método mostrou-se mais confiável. Os índices mostraram uma dominância do hemisfério direito para o estudo optocinético. Já, para os estudos rastreio e sacade, não verificamos essa dominância. Esse estudo permitiu a caracterização das mais freqüentemente áreas envolvidas nas tarefas de estimulação optocinética e dos movimentos de rastreio e sacade dos olhos. A combinação dessas tarefas constitui uma grande ferramenta para determinar a lateralização dessas funções e mapear as maiores áreas envolvidas nos sistemas oculomotor e vestibular. / Assessing inter-variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in clinical context. The main objective of this study is to analyze the variability of cerebral activation of the vestibular and oculomotor systems through an optokinetic horizontal, a pursuit and saccadic eye movement stimulations by means of fMRI. For this, images of magnetic resonance were acquired of twenty and three asymptomatic volunteers (thirteen for the optokinetic study and ten for the pursuit and saccade stimulations) in scanner of 1.5 T Siemens (Magneton Vision) with EPI-BOLD fMRI sequences. The statistical maps were analyzed in Brain Voyager software, using the method General Linear Model. We find significant activation in primary visual cortex, in middle and inferior occipital gyrus, in middle, superior and inferior temporal gyrus, in postcentral and precentral gyrus, in middle, inferior and superior frontal gyrus, in supramarginal gyrus, in superior and inferior parietal lobule, in insula and in anterior and posterior cingulate gyrus. Groups of activity had been also found in subcorticals structures (putamen, globus pallidus, corpus callosum and thalamus), beyond the cerebellum. The analysis of the activation frequency displays a high variability between volunteers. However, the most frequently activation regions were localized in areas frontals and in regions comprehending the middle and medial superior temporal gyrus. We use two methods for the analysis of the laterality index, the first admits a fixed statistical value and the second takes in consideration the dependence of the statistical threshold within the activated number of pixels, the second method revealed more reliability. The indices had shown a right hemisphere dominance for the optokinetic study but, for the pursuit and saccade stimulations, we do not verify this dominance. Our study allowed the characterization of the most frequently involved foci in tasks of optokinetic and pursuit and saccade eye movement stimulations. The combination of these tasks constitutes a suitable tool for determine the lateralization of these functions and for mapping major areas involved in the oculomotor and vestibular systems.

A avaliação da variabilidade inter-individual da atividade funcional é de grande importância na utilização da ressonância magnética funcional (fMRI) no contexto clínico. O objetivo principal desse estudo é analisar a variabilidade da ativação cerebral dos sistemas vestibular e oculomotor, através da fMRI em resposta à estimulação optocinética horizontal e aos movimentos de rastreio e sacade dos olhos. Para isso, imagens por ressonância magnética foram obtidas de vinte e três voluntários assintomáticos (treze para o estudo optocinético e dez para os estudos rastreio e sacade) em um scanner de 1.5 T Siemens (Magneton Vision) com seqüências do tipo EPI-BOLD. Os mapas estatísticos foram obtidos no programa Brain Voyager, utilizando o método Modelo Geral Linear. Encontramos ativação significante no córtex visual primário, ao longo do giro occipital médio e inferior, no giro temporal médio, superior e inferior, no giro pós- e pré-central, ao longo do giro frontal inferior, superior e médio, no giro supramarginal, no lobo parietal superior e inferior, na ínsula e no cíngulo anterior e posterior. Grupos de atividade também foram encontrados em estruturas subcorticais (putamen, globo pálido, corpo caloso e tálamo), além do cerebelo. A análise da freqüência de ativação revelou uma alta variabilidade entre voluntários. Contudo, as regiões com maior freqüência de ativação foram as áreas frontais e a área que compreende o giro temporal médio e médio superior. Utilizamos dois métodos para a análise dos índices de lateralização, o primeiro admite um valor estatístico fixo e o segundo leva em consideração a dependência do limiar estatístico com o número de pixels ativados, o segundo método mostrou-se mais confiável. Os índices mostraram uma dominância do hemisfério direito para o estudo optocinético. Já, para os estudos rastreio e sacade, não verificamos essa dominância. Esse estudo permitiu a caracterização das mais freqüentemente áreas envolvidas nas tarefas de estimulação optocinética e dos movimentos de rastreio e sacade dos olhos. A combinação dessas tarefas constitui uma grande ferramenta para determinar a lateralização dessas funções e mapear as maiores áreas envolvidas nos sistemas oculomotor e vestibular. / Assessing inter-variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in clinical context. The main objective of this study is to analyze the variability of cerebral activation of the vestibular and oculomotor systems through an optokinetic horizontal, a pursuit and saccadic eye movement stimulations by means of fMRI. For this, images of magnetic resonance were acquired of twenty and three asymptomatic volunteers (thirteen for the optokinetic study and ten for the pursuit and saccade stimulations) in scanner of 1.5 T Siemens (Magneton Vision) with EPI-BOLD fMRI sequences. The statistical maps were analyzed in Brain Voyager software, using the method General Linear Model. We find significant activation in primary visual cortex, in middle and inferior occipital gyrus, in middle, superior and inferior temporal gyrus, in postcentral and precentral gyrus, in middle, inferior and superior frontal gyrus, in supramarginal gyrus, in superior and inferior parietal lobule, in insula and in anterior and posterior cingulate gyrus. Groups of activity had been also found in subcorticals structures (putamen, globus pallidus, corpus callosum and thalamus), beyond the cerebellum. The analysis of the activation frequency displays a high variability between volunteers. However, the most frequently activation regions were localized in areas frontals and in regions comprehending the middle and medial superior temporal gyrus. We use two methods for the analysis of the laterality index, the first admits a fixed statistical value and the second takes in consideration the dependence of the statistical threshold within the activated number of pixels, the second method revealed more reliability. The indices had shown a right hemisphere dominance for the optokinetic study but, for the pursuit and saccade stimulations, we do not verify this dominance. Our study allowed the characterization of the most frequently involved foci in tasks of optokinetic and pursuit and saccade eye movement stimulations. The combination of these tasks constitutes a suitable tool for determine the lateralization of these functions and for mapping major areas involved in the oculomotor and vestibular systems.

Doctor of Philosophy / Department of Psychology / Lester C. Loschky / Öhman and Mineka (2001) proposed the existence of an evolved fear module with four Fodorian characteristics of modularity. They presented evidence that the fear module is selective, automatic, encapsulated, and operates in dedicated subcortical neural circuitry. The consistently rapid physiological and behavioral (attention capture) evidence (e.g., Öhman & Mineka, 2001) provides clear support for its automaticity. However, recent developments (e.g., Blanchette, 2006) cast doubt on the selectivity of the module. Specifically, it is unclear whether or not the fear module automatically responds selectively to evolutionarily ancient fear stimuli or whether modern threats may also elicit automatic responding. Furthermore, previous research using visual search paradigms has produced unclear results regarding the evolutionarily derived selectivity of the fear module. Unfortunately, the visual search method is notoriously sensitive to visual characteristics of stimuli (Duncan & Humphreys, 1989). However, eye movements provide a valid alternative measure of covert attention capture. In order to clarify the issues, Experiment 1 used an oculomotor inhibition paradigm to present ancient and modern threats with one another or neutral stimuli in competition for visual attention. In addition, we collected measures of participants’ experience with the stimuli to assess the influence of experience/familiarity/learning on rapid attention to threats. Furthermore, because image inversion maintains low level stimulus characteristics (e.g., spatial frequencies, contrast, and luminance) while disrupting the semantic processing of images, presenting the stimulus pairs upside down was used to determine whether any observed effects were due to low level stimulus characteristics. Experiment 1 produced null results with respect to systematic differences in attentional processes as a function of threat type. Because Experiment 1 was modeled after Nummenmaa et al., (2009, Exp 3), it was therefore necessary to attempt to replicate their findings. Experiment 2 successfully replicated the findings of Nummenmaa et al. Therefore, it is suggested that the rapid attention processes responsible for systematic deviations in saccade trajectories seen in Experiment 2 (and Nummenmaa et al., 2009, Exp 3) do not translate to the methodology used in Experiment 1. Given the findings from the present study, the question of whether or not there exists and evolved fear module remains open. This study clearly supports the existence of an attentional bias for emotional content as indicated through the use of oculomotor inhibition paradigm. However, like the visual search methodology, the oculomotor inhibition paradigm appears to be very sensitive to visual differences of the stimuli.

<p>Smooth pursuit eye movements are movements of the eyes that are used to foveate moving objects. Their precision and adaptation is believed to depend on a constellation of sites across the cerebellum, but only one region’s contribution is well characterized, the floccular complex. Here, I characterize the response properties of neurons in the oculomotor vermis, another major division of the oculomotor cerebellum whose role in pursuit remains unknown. I recorded Purkinje cells, the output neurons of this region, in two monkeys as they executed pursuit eye movements in response to step ramp target motion. The responses of these Purkinje cells in the oculomotor vermis were very different from responses that have been documented in the floccular complex. The simple spikes of these cells encoded movement direction in retinal, as opposed to muscle coordinates. They were less related to movement kinematics, and had smaller values of trial-by-trial correlations with pursuit speed, latency, and direction than their floccular complex counterparts. Unlike Purkinje cells in the floccular complex, simple spike firing rates in the oculomotor vermis remained unchanged over the course of pursuit adaptation, likely excluding the oculomotor vermis as a site of directional plasticity. Complex spikes of these Purkinje cells were only partially responsive to target motion, and did not fall into any clear opponent directional organization with simple spikes, as has been found in the floccular complex. In general, Purkinje cells in the oculomotor vermis were responsive to both pursuit and to saccadic eye movements, but maintained tuning for the direction of these movements along separate directions at a population level. Predictions of caudal fastigial nucleus activity, generated on the basis of our population of oculomotor vermal Purkinje cells, faithfully tracked moment-by-movement changes in pursuit kinematics. By contrast, these responses did not faithfully track moment-by-moments changes in saccade kinematics. These results suggest that the oculomotor vermis is likely to play a smaller role in influencing pursuit eye movements by comparison to the floccular complex.</p> / Dissertation

There have been few studies investigating the eye movement behavior of Parkinson’s disease patients during fixation. This study objectively measured the eye movements of 36 patients with Parkinson’s disease, and 20 age matched controls. Stimuli consisted of ten standardized text passages first organized by Miller and Coleman. In addition, subjects followed a randomly displaced step jump target motion. Pendular nystagmus was found in all Parkinson’s subjects, with an average frequency of 7.44 Hz. Saccadic peak velocity and duration along the main sequence were not statistically different from controls. A slower rate of reading was also noted in the Parkinson’s group in terms of characters per minute, but with no more regressions than normal. Rate of square wave jerks was also found to be normal. This suggests that the hallmark feature of eye movements in Parkinson’s disease is a pendular nystagmus during fixation, and all saccadic activity to be normal.

To date, invasive brain-computer interface (BCI) research has largely focused on replacing lost limb functions using signals from hand/arm areas of motor cortex. However, the oculomotor system may be better suited to BCI applications involving rapid serial selection from spatial targets, such as choosing from a set of possible words displayed on a computer screen in an augmentative and alternative communication application. First, we develop an intracortical oculomotor BCI based on the delayed saccade paradigm and demonstrate its feasibility to decode intended saccadic eye movement direction in primates. Using activity from three frontal cortical areas implicated in oculomotor production – dorsolateral prefrontal cortex, supplementary eye field, and frontal eye field – we could decode intended saccade direction in real time with high accuracy, particularly at contralateral locations. In a number of analyses in the decoding context, we investigated the amount of saccade-related information contained in different implant regions and in different neural measures. A novel neural measure using power in the 80-500 Hz band is proposed as the optimal signal for this BCI purpose. In the second part of this thesis, we characterize the interactions between the neural signals recorded from electrodes in these three implant areas. We employ a number of techniques to quantify the spectrotemporal dynamics in this complex network, and we describe the resulting functional connectivity patterns between the three implant regions in the context of eye-movement production. In addition, we compare and contrast the amount of saccade-related information present in the coupling strengths in the network, on both an electrode-to-electrode scale and an area-to-area scale. Different frequency bands stand out during different epochs of the task, and their information contents are distinct between implant regions. For example, the 13-30 Hz band stands out during the delay epoch, and the 8-12 Hz band is relevant during target and response epochs. This work extends the boundary of BCI research into the oculomotor domain, and invites potential applications by showing its feasibility. Furthermore, it elucidates the complex dynamics of the functional coupling underlying oculomotor production across multiple areas of frontal cortex.

The superior colliculus (SC) is a laminated oculomotor structure in the midbrain. In non-human primates SC has long been known to contain a retinotopically-organized map of visual stimulation in its superficial layers, which is aligned to a map of saccadic eye movements in the deeper layers. Microstimulation and electrophysiology experiments have shown that SC also plays a key role in covert visuospatial attention and suggest that attentional modulation also occurs in a retinotopic manner. Retinotopic organization of the visual field can be non-invasively mapped in humans using functional MRI with a technique called phase-encoded retinotopy. In this technique, rotating wedges and expanding rings of visual stimuli are used to map the polar angle and eccentricity dimensions of a polar coordinates system, respectively. A similar technique can also be used to map spatial attention by keeping the visual stimulus constant and cueing subjects to attend to apertures of rotating wedges and expanding rings within the stimulus. A previous study using fMRI has shown the polar angle representation of visual stimulation in human SC but was unable to find a representation of eccentricity. This work uses high-resolution fMRI along with special surface analysis techniques developed in our lab to demonstrate maps of both polar angle and eccentricity for visual stimulation. Moreover, visual attention is also shown to be topographically organized within SC and in registration with visual stimulation. Finally, in human visual cortex, fMRI is known to show activity for sustained spatial attention even in the absence of a significant visual stimulus, an attentional "base response". In this work, SC is shown to exhibit a similar sustained attention base response using a threshold-contrast detection paradigm. This base response was compared with a response for attention with visual stimulation. The peak amplitude of the base response occurred more deeply within SC tissue than the peak for attention with stimulation. It is proposed that this reflects the specific attentional enhancement of the deeper visuomotor neurons, which are hypothesized to be a direct neuronal correlate of the oculomotor theory of attention. / text

Nearly all imaginable human activities rest on a context-appropriate dynamic control of the flow of retinal data into the nervous system via eye movements. The brain’s task is to move the eyes so as to exert intelligent predictive control over the informational content of the retinal data stream. An intelligent oculomotor controller would first model future contingent upon each possible next action in the oculomotor repertoire, then rank-order the repertoire by assigning a value v(a,t) to each possible action a at each time t, and execute the oculomotor action with the highest predicted value each time. We present a striking evidence of such an intelligent neural control of human eyes in a laboratory task of visual search for a small target camouflaged by a natural-like stochastic texture, a task in which the value of fixating a given location naturally corresponds to the expected information gain about the unknown location of the target. Human searchers behave as if maintaining a map of beliefs (represented as probabilities) about the target location, updating their beliefs with visual data obtained on each fixation optimally using the Bayes Rule. On average, human eye movement patterns appear remarkably consistent with an intelligent strategy of moving eyes to maximize the expected information gain, but inconsistent with the strategy of always foveating the currently most likely location of the target (a prevalent intuition in the existing theories). We derive principled, simple, accurate, and robust mathematical formulas to compute belief and information value maps across the search area on each fixation (or time step). The formulas are exact expressions in the limiting cases of small amount of information extracted, which occurs when the number of potential target locations is infinite, or when the time step is vanishingly small (used for online control of fixation duration). Under these circumstances, the computation of information value map reduces to a linear filtering of beliefs on each time step, and beliefs can be maintained simply as running weighted averages. A model algorithm employing these simple computations captures many statistical properties of human eye movements in our search task. / text

This is a comparative study of eye movement behaviour of teleost fish from 5 families with diverse visual specialisations and oculomotor function. In chapter 3 I compared basic oculomotor parameters in three species of fish from the families Creediidae, Syngnathidae and Pinguipedidae, that show asynchronous eye movements and a fovea. All three species showed a close correlation between their specific retinal specialisation, oculomotor range and the lifestyles and feeding habits. Direction of gaze was correlated in the two independently moving eyes in both sandperch (Pinguipedidae) and pipefish (Syngnathidae) but not in the sandlance (Creediidae). Properties of spontaneous and fixational fast eye movements (saccades) in the species studied show many similarities to those found in other vertebrates. The apparent independence of the two eyes in the teleosts studied seem to set them apart from many other vertebrates, where eye movements are largely correlated with respect to each other. The results presented in chapter 4, however, reveal a regular switching of saccadic activity between the left and the right eye in sandlance, pipefish and sandperch, suggesting that the two eyes are in some way correlated. Since saccades are often a motor correlate of attention this finding suggests that these teleosts with asynchronous eye movements may show periodic shifts of attention while observing their environment. In chapter 5 the correlation between the two eyes was also tested during optokinetic nystagmus. This basic response shown by all animals stabilises the gaze against rotational head movements and translation. In most vertebrates the optokinetic response is tightly yoked in both eyes. This is also the case for the butterflyfish (Chaetodontidae) which shows strong yoking of the eyes during spontaneous eye movements. However some capacity for independent optokinesis in the two eyes was observed. Both sandlance and pipefish are capable of following two conflicting stimuli independently. However monocular occlusion in the pipefish unmasks a link between the two eyes, which is overridden when both eyes receive visual input. The sandlance never showed any correlation between eyes during optokinesis, even during monocular stimulation. This suggests that there are different levels of linkage between the two eyes in the oculomotor system of teleosts, depending on the visual input. One of the main functions of the oculomotor system in vertebrates and most invertebrates is to keep the image of the world relatively still on the retina. As shown in chapter 6 the sandlance breaks this universal rule of image stabilisation by showing large postsaccadic drifting eye movements as part of its normal oculomotor behaviour. In these animals, up to 40% of spontaneous saccades are followed by a drifting movement, either binocularly or in one eye only. The drifts are large and are always directed towards the most relaxed position of the eye, indicating that this form of eye movement is not visually driven. However the eye is visually responsive and saccades and an optokinetic response can be elicited during a drift. The drifting speed and the known acuity of the sandlance eye suggest that, during the drift, the image quality is not degraded. Several advantages of this unusual oculomotor behaviour can be related to the unusual optics and lifestyle of the sandlance. A unique modification of the eye muscles of billfish (Xiphiidae) maintains the eye and brain above ambient temperature; however the function of this adaptation and its effect on the oculomotor system is unknown. Chapter 7 aims to provide an insight into the visual abilities of billfish derived from anatomical observations of their retinal structure. The observations help explain the effect the increased retinal temperature might have for vision and eye movements. The blue marlin (Makaira nigricans) shows a well developed temporal area centralis and no visual streak, suggesting that a functional oculomotor system is required in this fish. A convergence of cones to ganglion cells at a ratio of at least 5:1 is present even in the area of highest acuity. The finding of two cone types suggest that the animal is capable of wavelength discrimination. Regional differences in size and composition of photoreceptors between dorsal and ventral retina potentially affect colour vision and sensitivity. The anatomical results suggest that sensitivity and spatial summation are of high priority to billfish. The possible function of the warm retina for increasing temporal resolution is discussed. These findings show the adaptability of the oculomotor system to suit the needs of different teleost lifestyles. However most of the parameters established for the oculomotor system of higher vertebrates also hold for teleosts.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.