京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第17819号 / 医博第3817号 / 新制||医||999(附属図書館) / 30634 / 京都大学大学院医学研究科医学専攻 / (主査)教授 金子 武嗣, 教授 大森 治紀, 教授 福山 秀直 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The vitreous cavity, the largest chamber of the eye, is delimited anteriorly by the lens and posteriorly by the retina and is filled by the vitreous humour. Under normal conditions the vitreous humour has the consistency of a gel, however, typically, with advancing age a disintegration of the gel structure occurs, leading to a vitreous liquefaction. Moreover, after a surgical procedure called vitrectomy the vitreous body may be completely removed and replaced by tamponade fluids. Besides allowing the establishment of an unhindered path of light from the lens to the retina, the vitreous also has important mechanical functions. In particular, it has the role of supporting the retina in contact to the outer layers of the eye, and of acting as a diffusion barrier for molecule transport between the anterior and the posterior segments of the eye. Studying the dynamics of the vitreous induced by eye rotations (saccadic movements) is important in connection of both the above aspects. On the one hand indications exist that the shear stress exerted by the vitreous on the retina may be connected with the occurrence of retinal detachment. On the other hand, if the vitreous motion is intense enough (a situation occurring either when the vitreous is liqueed or when it has been replaced with a uid after vitrectomy), advective transport may be by far more important than diffusion and may have complex characteristics. Advection has indeed been shown to play an important role in the transport phenomena within the vitreous cavity, but, so far, only advection due to the slow overall fluid ux from the anterior to the posterior segments of the eye has been accounted for, while fluid motion due to eye rotations, even if it is generally believed to play an important role, has been invariably disregarded. Some recent contributions have pointed out the importance of accounting for the real vitreous cavity shape in studying uid motion induced by eye rotations. Modelling the vitreous cavity as a deformed sphere, showed that the flow field displays very complex three- dimensional characteristics to which effective fluid mixing is likely to be associated. The purpose of the thesis is to model numerically the motion of the liqueed vitreous within the vitreous cavity induced by different eye movements. Create the model in the Comsol interface, compare the results with theoretical, experimental measurements and do some ow visualizations. Finally show the dependence of the streaming intensity from the amplitude of rotations and the Womersley number .

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Clinicians are becoming increasingly aware of the effect of various pathologieso n the characteristicso f saccadice ye movements.A s such, an efficient and non-invasivem eano f measuringe ye-movementisn a clinical environmenti s of interest to many. The aim of this thesis is to investigate the clinical application of a non-invasive eye movement recording technique as a part of a clinical examination. Eye movements were measured using an IRIS 6500 infrared limbal eye tracker, which we customized for the direct recording of oblique eye movements as well as horizontal and vertical. Firstly, the eye-tracker itself was assessed. Visually normal observers made saccadic eye movements to a 10' stimulus in eight directions of gaze. Primary (ANOVA) and secondary analyses (mean error less than 5%) resulted in acceptance that averaging four measurements would give a representative measurement of saccadic latency, peak velocity, amplitude and duration. Test-retest results indicated that this technique gives statistically (± 1.96*STDEVDifference) repeatable responses. Severalf actors that could potentially influence clinically basedm easureso f eye-movementsw ere examined. These included, the effect of ageing, viewing distances, dioptric blur and cataract. The results showed that saccadic latency and durationa re significantly (p< 0.05) longer in older (60-89 years)o bserversc ompared to younger (20-39 years). Peak velocity and amplitude were not significantly affectedb y the age of the observer.A ll saccadicp arameters( SP) were significantly affected by direction (Chapter 5). The compact nature of this eye movement methodology is obtainable since there is no significant effect on viewing distance (300 cm vs. 49 cm) (Chapter 6). There is also no significant effect of dioptric blur (up to +LOODS) on any of the four SP. In contrast, a higher level of defocus (+3.O ODS)h as a larger probability of interfering with the measurementso f peak velocity and duration (Chapter 7). Saccadice ye-movementsw ere also recorded whilst normally sighted subjects wore cataract simulation goggles. The results suggested that the presence of dense cataract introduces significant increases in saccadic latencies and durations. No effect was found on the peak velocities and amplitudes.T he effect of amblyopiao n SP was also investigatedin order to examine if this methodologyi s able to detectn ormal from abnormalr esponses(i . e. increased saccadicla tencies).T his set of data (Chapter9 ) showedt hat using IRIS 6500, longer than normal latencies may be recorded from the amblyopic eye but no consistent effect was found for the other SP (peak velocity, amplitude, duration). overall, the results of this thesis demonstrateth at the IRIS 6500 eye-tracker has many desirable elements (it is non-invasive; comfortable for the observers and gives repeatable and precise results in an acceptable time) that would potentially make it a useful clinical tool as a part of a routine examination.

Clinicians are becoming increasingly aware of the effect of various pathologies on the characteristics of saccadic eye movements. As such, an efficient and non-invasive means of measuring eye-movement in a clinical environment is of interest to many. The aim of this thesis is to investigate the clinical application of a non-invasive eye movement recording technique as a part of a clinical examination. Eye movements were measured using an IRIS 6500 infrared limbal eye tracker, which we customized for the direct recording of oblique eye movements as well as horizontal and vertical. Firstly, the eye-tracker itself was assessed. Visually normal observers made saccadic eye movements to a 10' stimulus in eight directions of gaze. Primary (ANOVA) and secondary analyses (mean error less than 5%) resulted in acceptance that averaging four measurements would give a representative measurement of saccadic latency, peak velocity, amplitude and duration. Test-retest results indicated that this technique gives statistically (± 1.96*STDEVDifference) repeatable responses. Several factors that could potentially influence clinically based measures of eye-movements were examined. These included, the effect of ageing, viewing distances, dioptric blur and cataract. The results showed that saccadic latency and duration are significantly (p < 0.05) longer in older (60-89 years) observers compared to younger (20-39 years). Peak velocity and amplitude were not significantly affected by the age of the observer. All saccadic parameters (SP) were significantly affected by direction (Chapter 5). The compact nature of this eye movement methodology is obtainable since there is no significant effect on viewing distance (300 cm vs. 49 cm) (Chapter 6). There is also no significant effect of dioptric blur (up to +LOODS) on any of the four SP. In contrast, a higher level of defocus (+3.O ODS) has a larger probability of interfering with the measurements of peak velocity and duration (Chapter 7). Saccadic eye-movements were also recorded whilst normally sighted subjects wore cataract simulation goggles. The results suggested that the presence of dense cataract introduces significant increases in saccadic latencies and durations. No effect was found on the peak velocities and amplitudes. The effect of amblyopia on SP was also investigated in order to examine if this methodology is able to detect normal from abnormal responses (i.e. increased saccadic latencies). This set of data (Chapter9 ) showed that using IRIS 6500, longer than normal latencies may be recorded from the amblyopic eye but no consistent effect was found for the other SP (peak velocity, amplitude, duration). Overall, the results of this thesis demonstrate that the IRIS 6500 eye-tracker has many desirable elements (it is non-invasive; comfortable for the observers and gives repeatable and precise results in an acceptable time) that would potentially make it a useful clinical tool as a part of a routine examination.

The Remote Distractor Effect (RDE) is a robust phenomenon where a saccade to a lateralised target is delayed by the appearance of a distractor in the contralateral hemifield (Walker, Kentridge, & Findlay, 1995). The main aim of this thesis was to test whether the RDE generalises to response modalities other then the eyes. In Chapter 2, the RDE was tested on saccadic and simple manual keypress responses, and on a choice discrimination task requiring a covert shift of attention. The RDE was observed for saccades, but not simple manual responses, suggesting that spatially oriented responses may be necessary for the phenomenon. However, it was unclear whether distractor interference occurred in the covert task. Chapter 4 compared the effects of distractors between spatially equivalent tasks requiring saccadic and manual aiming responses respectively. Again, the RDE was observed for the eyes but not for the hands. This dissociation was also replicated in a more naturalistic task in which participants were free to move their eyes during manual aiming. In order to examine the time-course of distractor effects for the eyes and the hands, a third experiment investigated distractor effects across a wider range of target-distractor delays, finding no RDE for manual aiming responses at distractor delays of 0, 100, or 150 ms. The failure of the RDE to generalise to manual aiming suggests that target selection mechanisms are not shared between hand and eye movements. Chapter 5 further investigated the role of distractors during covert discrimination. The first experiment showed that distractor appearance did not interfere with discrimination performance. A second experiment, in which participants were also asked to saccade toward the target, confirmed the lack of RDE for covert discrimination while saccades were slower in distractor trials. The dissociation between covert and overt orienting suggests important differences between shifts of covert attention and preparation of eye movements. Finally, Chapter 6 investigated the mechanism driving the RDE. In particular it was assessed whether saccadic inhibition (Reingold & Stampe, 2002) is responsible for the increase in saccadic latency induced by remote distractors. Examination of the distributions of saccadic latencies at different distractor delays showed that each distractor produced a discrete dip in saccadic frequency, time-locked to distractor onset, conforming closely to the character of saccadic inhibition. It is concluded that saccadic inhibition underlies the remote distractor effect.

Deal or no deal? Hold ‘em or fold ‘em? Buy, hold or sell? When faced with uncertainty, a wise decision-maker evaluates each option and chooses the one they deem most valuable. Scientists studying decision making processes have spent much theoretical and experimental effort formalizing a framework that captures how decision makers can maximize the amount of subjective value they accrue from such decisions. This thesis tested two hypotheses. The first was that subjective value guides our simplest and most common of motor actions similar to how it guides more deliberative economic decisions. The second was that subjective value is allocated across pre-motor regions of the brain to make our actions more efficient. To accomplish these goals, I adapted a paradigm used by behavioural economists for use in neurophysiological experiments in non-human primates. In our task, monkeys repeatedly make quick, orienting eye movements, known as saccades, to targets, which they learned through experience, had different values. In support of the hypothesis that subjective value influences simple motor actions, the speed with which monkeys responded, known as saccadic reaction time (SRT), and their saccadic choices to valued targets were highly correlated and therefore both acted as a behavioural measures of subjective value. Two complimentary results support the hypothesis that subjective value influences activity in the intermediate layers of the superior colliculus (SCi) – a well-studied brain region important to the planning and execution of saccades - to produce efficient actions. First, when saccades were elicited with microstimulation, we found that the timing and spatial allocation of pre-saccadic activity in the SC was shaped by subjective value. Second, the baseline preparatory activity and transient visual activity of SCi neurons prior to saccade generation was also influenced by subjective value. Our results can be incorporated into existing models of SC functioning that use dynamic neural field theory. I suggest that saccades of higher subjective value will result in higher activation of their associated neural field such that they will be more likely and more quickly selected. In summary, this thesis demonstrates that subjective value influences neural mechanisms, not only for deliberative decision making, but also for the efficient selection of simple motor actions. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2013-06-25 17:18:25.393

O presente estudo teve como objetivo avaliar o efeito da incerteza a respeito da direção do deslocamento de um alvo na estratégia visual e controle motor em uma tarefa de interceptação. Participaram do Experimento I 17 voluntários, executando movimentos manuais interceptativos de um alvo virtual projetado em uma tela de LCD. A tarefa interceptativa foi executada com um mouse sem fio. Os participantes foram submetidos a três condições experimentais em duas velocidades: (1) certeza de descolamento com direção inicial do alvo inalterada, (2) 50% de incerteza de mudança na direção de deslocamento do alvo, e (3) certeza de mudança na direção de deslocamento do alvo. Participaram do Experimento II 20 voluntários destros diferentes dos do experimento anterior, que executaram a mesma tarefa descrita no Experimento I. Dez voluntários integraram o grupo que recebeu informação prévia sobre a probabilidade de deslocamento do alvo antes de cada série de tentativas (INF), e os demais integraram o grupo que não recebeu informação prévia (SI). Ambos os grupos foram submetidos a três condições de avaliação: (1) 25% de certeza de mudança na direção do alvo, (2) 50% de certeza de mudança na direção do alvo, e (3) 75% de certeza de mudança na direção do alvo. Os resultados revelaram que o comportamento visual é modulado pela velocidade e incerteza sobre o deslocamento do alvo. Foi encontrado também que o conhecimento prévio sobre a probabilidade de deslocamento do alvo influenciou a estratégia visual utilizada e o desempenho da interceptação. Comportamentos preditivos foram evidenciados tanto no comportamento visual quanto no motor / The present study aimed to evaluate the effect of uncertainty about direction of target displacement on the visual strategy and motor control in an interception task. Seventeen volunteers participated of Experiment I. They performed interceptive manual movements of a virtual target projected on a LCD screen. The task was performed with a wireless mouse. Participants were submitted to three experimental conditions in two speeds: (1) certainty about unchanged initial target displacement direction, (2) 50% of uncertainty about change of target displacement direction, and (3) certainty about change of initial target displacement direction. Twenty volunteers different from Experiment I participated of Experiment II. Participants performed the same task described in the first experiment. Ten volunteers were assigned to a group which received prior information about the probability of displacement of the target before each condition (INF), and the others were assigned to a group that received no prior information (SI). The groups were evaluated in three conditions: 25%, 50% and 75% of uncertainty about change of target direction. Results of this study revealed that visual behavior is modulated by target speed and uncertainty about the target\'s motion. We also found that prior knowledge about the probability of the target\'s movement influenced the visual strategy used and the performance of the interception. Predictive behaviors were evidenced in both the visual and motor behavior

The Where's Waldo problem concerns how individuals can rapidly scan a scene to detect a target object in it. This dissertation develops the ARTSCAN Search neural model to clarify how brain mechanisms that govern spatial and object attention, spatially-invariant object learning and recognition, reinforcement learning, and eye movement search are coordinated to enable learning and directed search for desired objects at specific locations in a cluttered scene. In the model, interactions from the Where cortical processing stream to the What cortical processing stream modulate invariant category learning of a desired object, whereas interactions from the What cortical processing stream to the Where cortical processing stream support search for the object. In particular, when an invariant object category representation is activated top-down by a cognitive plan or by an active motivational source in the model's What stream, it can shift spatial attention in the Where stream and thereby selectively activate the locations of sought-after object exemplars. These combined What-to-Where and Where-to-What interactions clarify how the brain's solution of the Where's Waldo problem overcomes the complementary deficiencies of What and Where stream processes taken individually by using inter-stream interactions that allow both invariant object recognition and spatially selective attention and action to occur.

Right parietal lesions often lead to neglect, in which patients fail to attend to leftward stimuli. Recent models of neglect suggest that, in addition to attentional impairments, patients demonstrate impairments of spatial remapping and/or spatial working memory (SWM). Although spatial remapping could be considered a kind of spatial memory process itself (i.e., updating remembered locations based on anticipated saccade outcomes), the two processes operate on very different time scales (milliseconds versus seconds). In the present study, the influence of saccadic and spatial remapping on SWM was examined in healthy individuals. An initial control condition, in which participants had to respond to a probe stimulus (i.e., “is the probe in the location previously occupied by the target?”) following a 1500 ms delay, was contrasted with conditions in which the fixation point moved (left, right, up, or down) at the onset of the delay. In a second version of the task, participants made covert shifts of attention at delay onset requiring covert spatial, rather than saccadic, remapping. In both tasks SWM performance was best when no remapping was required. Decrements in SWM were largest overall in the spatial remapping task, whereas for both saccadic and spatial remapping, a consistent cost was observed for remapping the target array into right visual space. Results are discussed in terms of hemispheric biases in attention and differences in performance for peripersonal versus extrapersonal space.