Autism Spectrum disorder (ASD) is a wide ranging developmental condition commonly recognised by impairments in social interaction, communication, repetitive behaviour and restricted interests. Deficits in imitation, sensory processing and motor control are also extensive, but conflicting findings mean a clear picture regarding the true nature of these is yet to be established. The aim of this thesis was to further investigate imitation with a specific focus on the effect of goals. It has been suggested that imitation occurs along two routes; a direct route for the imitation of meaningless actions i.e. goal-less, and a semantic route for meaningful or goal-directed actions. There is evidence to suggest that while individuals with ASD may have an impairment in goal-less imitation, goal-directed imitation is unaffected (Hamilton, Brindley & Frith, 2007). The experiments in the present work were based on the hypothesis that impaired goal-less imitation in ASD may be due to a problem with sensory motor integration in the direct visuomotor pathway for imitation (Tessari and Rumiati, 2004).The first experiment was conducted to ascertain whether movement kinematics differed between imitation during goal-directed and goal-less hand movements in a neurotypical control group. Participants observed and imitated hand movements of different speeds, while their movement was recorded with a motion sensor. Movement was modulated between the different speeds in the goal-less, but not goal-directed trials. These findings support the dual route model where visuomotor mapping occurs via the direct pathway during goal-less imitation but during goal-directed imitation there is greater reliance on representations of actions from long term memory.In experiment two, the same paradigm was employed, including additional movement types, and a group of adult individuals diagnosed with an ASD was compared to a control group. It was predicted that, unlike the control group, the ASD group would fail to modulate their movement in the goal-less condition, due to a disruption in the direct pathway. Eye movements were also recorded in this experiment, to ascertain if differences in gaze position or eye movements might influence the ability of the ASD group to imitate goal-less actions. The ASD group did not modulate their movement for goal-less imitation. In addition, the ASD group exhibited more goal-directed gaze, and less gaze toward the hand, than the control group. The ASD group also failed to maintain pursuit of the hand, which may have influenced the amount of information collected regarding the movement.The third study extended the investigation by introducing a training phase halfway through the experiment. Based on eye movement findings, it was hypothesised that drawing attention to the hand might increase the importance of the hand in goal-less trials, subsequently leading to increased tracking, and improved imitation. Perspective was also investigated to determine whether observing the action from an egocentric perspective would improve imitation. Movement modulation was not improved for either the post training or the egocentric condition. However, both training and egocentric viewing resulted in faster performance of movements while training also reduced the amount of movement variability; suggesting that these conditions made imitation easier. Findings strongly support the hypothesis that people with ASD are impaired in goal-less but not goal-directed imitation. These results are discussed in terms of bottom-up and top-down influences on imitation. The observed eye movement differences between the ASD and control group suggest eye movement abnormalities, and the finding that egocentric observation facilitates imitation indicates problems with visuospatial transformation during allocentric imitation. Finally, failure to pursue may be due to lack of attention to the hand movement, evidenced by no increase in pursuit after training. This thesis concludes with the suggestion that impaired goal-less imitation in ASD may result primarily from bottom-up low level visual processing and oculomotor control problems, combined with a high level attentional mechanism. Future studies need to address whether these are the primary causes of imitation difficulties, or whether there is a fundamental sensory motor integration deficit in ASD.

Les informations visuelles sont prépondérantes pour guider le comportement. Malgré une bonne connaissance du système visuel, un phénomène représentant une latéralisation de celui-ci, le phénomène de dominance oculaire (DO), reste mal compris et finalement peu étudié. Nos travaux de thèse ont permis de démontrer que cette DO exerce une large influence sur différentes étapes de la transformation des informations visuelles en mouvements manuels ou oculaires et que celle-ci s’exprime en interaction avec d’autres latéralisations du système nerveux telles que les latéralisations manuelle et des réseaux attentionnels. Nous montrons également son influence sur les processus de transfert d'information entre les deux hémisphères du cerveau. Enfin, nos travaux comportent des retombées cliniques directes : ils introduisent une méthode de quantification plus précise de la DO utilisable par les cliniciens pour une meilleure réussite de certaines techniques chirurgicales. En conclusion, nous montrons que la DO constitue un aspect important de la latéralisation du cerveau humain, relativement négligé jusqu’à présent. / Processing of visual information from the environment is preponderant for the successful performance of many motor behaviors. Despite a good knowledge of the visual system, a phenomenon corresponding to a lateralization of this system, called eye dominance (ED), remains not well understood and poorly studied. Our thesis demonstrated that ED has a widespread influence on different levels of the transformation of visual information into manual or ocular movements and interacts with other lateralizations of the central nervous system such as the manual and attentional networks. We also show the influence of ED on the process of information transfer between the two hemispheres of the brain. Finally, our work has direct clinical implications: it introduces a more accurate method of quantifying ED which is usable by clinicians for better success of some surgical techniques. In sum, we show that ED is an important aspect of the human brain lateralization which has been overlooked until now.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20967号 / 医博第4313号 / 新制||医||1026(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 村井 俊哉, 教授 松田 秀一, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Healthy individuals can adjust their movements when changes arise to the body or the environment. Advanced age is associated with central and peripheral changes that may negatively impact one’s ability to adapt motor performance, such us upper-limb (UL) reaching movements. In this thesis, we conducted four studies to address the impact of aging on coordination and adaptation of goal-directed reaches. In the first experiment, we examined compensatory arm–trunk coordination in older adults during trunk-assisted reaching, using two motor tasks : 1) the Stationary Hand Task (SHT) in which older and young participants were asked to maintain a fixed hand position while flexing forward at the trunk, and 2) the Reaching Hand Task (RHT) in which participants were instructed to reach to a within-arm’s reach target while simultaneously flexing forward at the trunk (Raptis et al., 2007; Sibindi et al., 2013). We found that in SHT, young and older participants were able to maintain a stable hand position and compensate for trunk movement by appropriate angular rotations at the elbow and shoulder joints. As well, in the RHT, both groups made similar small overshoot errors. However, older participants performance was significantly more variable compared to young adults. These results suggest that older adult preserve their ability to coordinate arm and trunk movements efficiently during reaching but are not as consistent as young adults. In the second experiment, we sought to determine the ability of older adults to adjust shoulder and elbow coordination in response to changing task demands. Thus, we asked young and older adults to perform the RHT of Raptis et al. (2007) from the first experiment. A detailed comparison of UL kinematics during reaches in the presence and absence of trunk motion (i.e., free- vs. blocked-trunk trials) was performed and compared between young and older adults. We found that participants in both age group were able to coordinate motion at the elbow and shoulder joints in accordance with motion at the trunk. However, the extent of changes at the UL joints was smaller and more variable in older adults compared to young ones, especially when trunk motion was involved. These results imply that older adults can coordinate their UL movements based on task requirements, but with less consistent performance compared to young adults. In the third experiment, we investigated the preservation of intermanual transfer and retention of implicit visuomotor adaptation in older adults. We had young and older participants train to reach with visual feedback rotated 30° counter-clockwise relative to their actual hand motion. Furthermore, we examined whether providing augmented somatosensory feedback regarding movement endpoint would enhance visuomotor adaptation. We found that older adults demonstrated a comparable magnitude of implicit adaptation, transfer, and retention of visuomotor adaptation as observed in young adults, regardless of the presence of augmented somatosensory feedback. These results indicate that intermanual transfer and retention do not differ significantly between young and older adults when adaptation is driven implicitly, regardless the availability of augmented somatosensory feedback. In the fourth experiment, we looked to determine age-related differences in the engagement of offline and online control processes during implicit visuomotor adaptation. A detailed analysis of reaching performance was conducted and between young and older adults, during and after visuomotor adaptation. We found that when rotation was introduced, participants in both age took longer time to complete their movements, reached with a lower peak velocity and spent more time homing in on the target compared to reaches with aligned cursor feedback. Additionally, older adults had more curved paths with rotated cursor feedback compared to their reaches with aligned cursor feedback. Moreover, these changes in reaching performance continued following adaptation for both groups. These results suggest that young and older adults engage more in online control processes during implicit visuomotor adaptation. Together, these studies show that older adults: 1) maintain the ability to use compensatory arm-trunk coordination to maintain reaching accuracy, 2) preserve the ability to adjust the coordination between UL joints to meet task demands, 3) maintain the ability to adjust reaches to meet changes in the reaching environment, as well as transfer and retain the newly acquired movement, and 4) preserve the ability to modify the control processes underlying these adapted movements to meet the demands of the reaching environment. In conclusion, the flexibility to coordinate and adapt upper limb reaching performance to meet changes in task demands is maintained across lifespan.

At least 2.6 billion people all over the world suffer from nearsightedness, among whom 312 million are under 19 years old. Just like other vision problems, uncorrected nearsightedness brings inconvenience to many human daily activities including walking. However, the influence of nearsightedness on gait patterns and gaze behaviours remains barely discovered. This project aimed to study the influence of nearsightedness on human visuomotor coordination in different environmental settings. An integrated system combining motion capture and eye-tracking was implemented for measuring gait and gaze simultaneously. Twelve participants were recruited to perform a protocol consisting of walking tasks in various visual and environmental conditions. Nine of the participants were eligible for data analysis. Gaze time distribution and gait cycle parameters were compared between participant groups (five with normal vision, four nearsighted), and among different walking tasks. Results revealed that comparing with the control group, the nearsighted participants made shorter and slower steps, as well as spent more time looking at the walking path. The walking path also affected the gait and gaze behaviours, with shorter step length and longer step time observed when the participants were walking uphill, while increased gaze attention was paid downhill. The practicality of combining gait analysis with eye-tracking was proved in this project, laying a foundation for future studies of visuomotor coordination.

Recent technological developments have ushered in an exciting era for collaborative robots (cobots), which can operate in close proximity with humans, sharing and supporting task goals. While there is increasing research on the biomechanical and ergonomic consequences of using cobots, there is relatively little work on the potential motor-cognitive demand associated with these devices. These cognitive demands primarily stem from the need to form accurate internal (mental) models of robot behavior, while also dealing with the intrinsic motor-cognitive demands of physical co-manipulation tasks, and visually monitoring the environment to ensure safe operation. The primary aim of this work was to investigate the viability of eye-tracking measures for characterizing mental workload during the use of cobots, while accounting for the potential effects of learning, task-type, expertise, and age-differences. While eye-tracking is gaining traction in surgical/rehabilitation robotics domains, systematic investigations of eye tracking for studying interactions with industrial cobots are currently lacking. We conducted three studies in which participants of different ages and expertise levels learned to perform upper- and lower-limb tasks using a dual-armed cobot and a whole-body powered exoskeleton respectively, over multiple trials. Robot-control difficulty was manipulated by changing the joint impedance on one of the robot arms (for the dual-armed cobot). The first study demonstrated that when individuals were learning to interact with a dual-armed cobot to perform an upper-limb co-manipulation task simulated in a virtual reality (VR) environment, pupil dilation (PD) and stationary gaze entropy (SGE) were the most sensitive and reliable measures of mental workload. A combination of eye-tracking measures predicted performance with greater accuracy than experimental task variables. Measures of visual attentional focus were more sensitive to task difficulty manipulations than typical eye-tracking workload measures, and PD was most sensitive to changes in workload over learning. The second study showed that compared to walking freely, walking while using a complex whole-body powered exoskeleton: a) increased PD of novices but not experts, b) led to reduced SGE in both groups and c) led to greater downward focused gaze (on the walking path) in experts compared to novices. In the third study using an upper-limb co-manipulation task similar to Study 1, we found that the PD of younger adults reduced at a faster rate over learning, compared to that of older adults, and older adults showed a significantly greater drop in gaze transition entropy with an increase in task difficulty, compared to younger adults. Also, PD was sensitive to learning and robot-difficulty but not environmental-complexity (collisions with objects in the task environment), and gaze-behavior measures were generally more sensitive to environmental-complexity. This research is the first to conduct a comprehensive analysis of mental workload in physical human-robot interaction using eye-tracking measures. PD was consistently found to show larger effects over learning, compared to task difficulty. Gaze-behavior measures quantifying visual attention towards environmental areas of interest were found to show relatively large effects of task difficulty and should continue to be explored in future research. While walking in a powered exoskeleton, both novices and experts exhibited compensatory gaze strategies. This finding highlights potentially persistent effects of using cobots on visual attention, with potential implications to safety and situational awareness. Older adults were found to apply greater mental effort (indicated by sustained PD) and followed more constrained gaze patterns in order to maintain similar levels of performance to younger adults. Perceived workload measures could not capture these age-differences, thus highlighting the advantages of eye-tracking measures. Lastly, the differential sensitivity of pupillary- and gaze behavior metrics to different types of task demands highlights the need for future research to employ both kinds of measures for evaluating pHRI. Important questions for future research are the potential sensitivity of eye-tracking workload measures over long-term adaptations to cobots, and the potential generalizability of eye-tracking measures to real-world (non-VR) tasks. / Doctor of Philosophy / Collaborative robots (cobots) are an exciting and novel technology that may be used to assist human workers in manual industrial work, reduce physical demand, and potentially enable older adults to re-enter the workforce. However, relatively little is known about the potential cognitive demands that cobots may impose on the human user. Although intended to assist humans, some cobots have been found to be difficult to use, because of the time and effort that is needed to learn their control dynamics (i.e. to learn how to physically control them to perform a complex manual task). Thus, it is important to better understand the potential mental demand/workload that a human operator may experience, while using a cobot, and how this demand may vary over time and learning to use the cobot. Eye-tracking is a promising technique to measure a cobot-operators' mental workload, since it can provide various measures that correlate with the involuntary physiological response to mental workload (e.g. pupil dilation - PD), as well as voluntary gaze strategies (e.g. the durations and patterns of where people look) in order to perform a physical/motor task. Eye-tracking measures may be used to continuously and precisely evaluate whether a cobot imposes excessive workload on the human operator, and if high workload is observed, the cobot may be programmed to adapt its behavior to reduce workload. Although eye-tracking is gaining traction in surgical/rehabilitation robotics domains, systematic investigations of eye tracking for studying interactions with industrial cobots are currently lacking. We designed three studies in which we investigated 1) the ability of eye-tracking measures to measure changes in mental workload while participants learned to use a cobot under different difficulty-levels 2) the changes in pupil diameter and gaze behavior when participants walked while wearing a whole-body powered exoskeleton as opposed to walking freely, and potential differences between novice- and expert exoskeleton-users 3) the differences in mental workload and visual attention between younger and older adults while learning to use a cobot. The first and third studies used virtual reality (VR) to simulate the task environment, to allow for precise control over the presentation of stimuli. In study 1, we found that in higher difficulty-levels, participants' pupils were significantly more dilated, i.e., participants experienced higher mental workload, than in lower-difficulty levels. Also, PD gradually reduced as participants learned to better perform the task. In difficult task-conditions, participants gazed more frequently at the robot, and showed higher randomness (entropy) in their gaze patterns. The proportion of gaze falling on certain objects was at least as sensitive an indicator of task-difficulty, as PD and gaze entropy. In study 2, we found that walking in a whole-body exoskeleton was cognitively demanding, but only for novice participants. However, both novice and expert participants showed changes in their gaze patterns while walking in the exoskeleton – both groups lowered their gaze and focused on the walking path to a greater extent, compared to walking freely. Lastly, in study 3, we also found that older adults applied greater mental effort for maintaining similar levels of performance as younger adults. Older adults also exhibited more repetitive scanning patterns compared to younger adults, when task difficulty increased. This may have been due to potential reduction in the capacity to control attention with age. Our work demonstrates that eye-tracking measures are sensitive and reliable metrics of workload, and that different metrics are sensitive to different sources of workload. Specifically, PD was sensitive to robot-difficulty, and measures of visual attention were generally more sensitive to the complexity of the task environment. Important questions for future research are the potential changes in eye-tracking workload measures over longer time periods of learning to use cobots, and how these results generalize to real-world tasks that are not performed in virtual reality.

Yes / Huntington’s disease (HD) is associated with impairments in dual-task performance. Despite that, only a few studies have investigated dual-tasking in HD. We examined dual-task performance in 15 participants in the early stages of HD and 15 healthy controls. Participants performed direct circle tracing (able to view arm) and indirect circle tracing (arm obscured) either on their own (single tasks) or paired with serial subtraction by twos or threes (dual tasks). Overall, our results suggested that HD participants were significantly slower and less accurate than controls. Both groups were slower and less accurate when performing indirect circle tracing compared with direct circle tracing. HD participants experienced greater dual-task interference in terms of accuracy when performing direct circle tracing compared with indirect circle tracing. Despite that, controls were more inclined to speed–accuracy trade-offs compared with HD participants. Importantly, unlike controls, HD participants were not disproportionately faster when performing direct circle tracing as a single task compared with the dual-task conditions. Our results suggest that simple tasks place greater attentional demands on HD participants compared with controls. These findings support that impaired automaticity may be responsible for some of the attentional deficits manifested in HD. / Supported by the School of Psychological Sciences, Monash University.

Yes / The aim of this study was to investigate age-related differences in dual task performance by using an upper limb proprioceptive task. Twenty-eight younger (18–30 years) and 28 older (>60 years) healthy adults performed circle tracing and serial subtraction tasks separately and concurrently. The tasks had two levels of difficulty: easy and hard. The circle tracing task included direct (easy) and indirect (hard) visual feedback conditions, and it was paired with serial subtraction by twos (easy) or threes (hard). We found that older adults were significantly slower than younger adults across all conditions and had significantly greater dual task costs when they performed circle tracing with easy serial subtraction. Higher levels of task difficulty were associated with slower speed in both groups. We found no age differences in accuracy. Participants either traded speed for accuracy or accuracy for speed regardless of age group. Overall, the findings suggest that speed and accuracy may be affected differently during dual tasking. In addition, older adults may rely more extensively on proprioceptive feedback to guide upper limb movement compared with younger adults. / Financial support for this study was obtained from the School of Psychology and Psychiatry, Monash University.

Essential tremor (ET) is the most common movement disorder worldwide and is characterized by an isolated tremor of the upper limb that worsens over the course of time. Evidence has accumulated to support the theory that the cerebellum is primary involved in the development of ET disease, although the contribution of cerebellar pathology to ET’s aetiology remains poorly understood. Beside motor deficits, numerous studies report the presence of cognitive impairment in ET patients. The cerebellum is crucial for motor as well as cognitive functions as it integrates sensorimotor information to create an internal model of movement using prediction errors. In this study, I tested the performance of 34 ET patients and 34 age-matched healthy controls in a visuomotor adaptation (VMA) task whose proper execution critically depends on the cerebellum. Participants performed the VMA while sitting in front of a computer screen. At the beginning of each trial, eight grey circles in one of eight possible positions arrayed around a central cross appeared on the screen. Next, one of the eight circles was marked as a blue target, and participants had to move from the central cross towards the target using a digital pen moved on a digital tablet. The movement on the tablet was represented as a cursor on the screen. Visual feedback from the moving hand was prevented. Over the course of the experiment, a 30° clockwise visuomotor perturbation of the cursor movement on the screen was introduced abruptly. To this end, subjects implicitly modified the reach direction such that they are able to hit the target again. The extent to which a subject adapts to the visuomotor perturbation can be measured by the angular error between a straight line connecting the center cross and the target, and a line connecting the center cross and the position of the cursor at peak velocity. Reaction times and movement times were analyzed to assess motor performance. In accordance with my hypothesis, I found evidence for impaired visuomotor adaptation in ET that could not be explained by altered general motor performance due to tremor. This deficit was also specific to both early and late adaptation phases. There were no group differences during a baseline phase, in which no visual perturbation was present, as well as at a de-adaptation phase, when the visual perturbation was suddenly removed. This deficit seems to also not relate to clinical features, i.e., disease state (measured by TETRAS/SARA), disease duration, current medication, and patients’ cognitive state (evaluated by MoCA). Thus, these findings support the hypothesis that a functional disturbance of the cerebellum is present in mildly to moderately affected ET patients without marked cerebellar signs and is detectable using a behavioral task that targets cerebellar functionality. What could be further mechanisms that negatively affect visuomotor adaptation in patients with ET and are not associated with basic motor functions? Unlike a pure motor task, the visuomotor adaptation task entails a cognitive component with implicit and/or explicit learning processes. Thus, it could be that cognitive deficits in ET, frequently reported among studies may have driven performance deficits in this task. Note however that I did not find any association between cognitive abilities as measured by MoCA and visuomotor adaptation impairment in the ET cohort. As no extensive neurocognitive testing was performed in our cohort and MoCA was shown to be not very sensitive for cerebellar cognitive symptoms, it is impossible to rule out the effect of cognitive decline in ET on visuomotor adaptation.

El aprendizaje visuomotor condicional es un paradigma en el que las asociaciones estímulo-respuesta se aprenden a través de una recompensa. Un experimento típico se desarrolla de la siguiente forma: cuando se presenta un estímulo a un sujeto, éste debe decidir qué acción realizar de entre un conjunto. Una vez seleccionada la acción, el sujeto recibirá una recompensa en el caso de que la acción escogida sea correcta. En este tipo de tareas interactúan distintas regiones cerebrales, entre las que destacan el córtex prefrontal, el córtex premotor, el hipocampo y los ganglios basales. El objetivo de este proyecto consiste en estudiar la dinámica neuronal subyacente a esta clase de tareas a través de modelos computacionales. Proponemos el término processing pathway para describir cómo ejecuta esta tarea el cerebro y explicar los roles e interacciones entre las distintas áreas cerebrales. Además, tratamos el procesamiento anómalo en una hipótesis neurodinámica de la esquizofrenia. / Conditional visuomotor learning is a paradigm in which stimulus-response associations are learned upon reward feedback. A typical experiment is as follows: Upon a stimulus presentation, a subject has to decide which action to choose among a number of actions. After an action is selected, the subject receives reward if the action was correct. Several interacting brain regions work together to perform this task, most prominently the prefrontal cortex, the premotor cortex, the hippocampus, and the basal ganglia. Using computational modeling, we analyze and discuss the neurodynamics underlying this task. We propose the term processing pathway to describe how the brain performs this task and detail the roles and interactions of the brain regions. In addition, we address aberrant processing in a neurodynamical hypothesis of schizophrenia.