Backward Walking: A Novel Marker Of Fall Risk, Cognitive Dysfunction, And Myelin Damage In Persons With Multiple Sclerosis

Multiple sclerosis (MS) is a progressive, neurologic disease of the central nervous system that causes debilitating motor, sensory and cognitive impairments. As a result, persons with MS are at an increased risk for falls and falls represent a serious public health concern for the MS population. The current clinical measures used to assess fall risk in MS patients lack sensitivity and predictive validity for falls and are limited in their ability to capture to multiple functional domains (i.e., motor, sensory, cognitive and pathological domains) that are impaired by MS. Backward walking sensitively detects falls in the elderly and other neurologic diseases. However, backward walking and falls has never been explored in the MS population and the underlying reasons as to why backward walking sensitively detects falls remains unknown. Identification of a quick, simply and clinically feasible fall risk measures related to multiple functions impacted by MS and related to fall risk, which can detect falls before they occur is critical for fall prevention and timely and targeted intervention. Therefore, this dissertation examines backward walking as a novel marker of fall risk and its cognitive and pathological underpinnings to support its clinical utility. Our results indicate that backward walking is a sensitive marker of fall risk in the MS population, regardless of co-morbid cognitive deficits, and that examining underlying brain regions likely to contribute to backward walking performance including the corticospinal tract, corpus callosum and cerebellum, with neuroimaging tools sensitive to myelin (i.e., Myelin Water Imaging) demonstrate potential to identify underlying mechanisms of backward walking performance in the MS population. This work is the critical first step in establishing backward walking as a sensitive marker of fall risk for the MS population and leads the way to more personalized fall prevention therapies and interventions to improve clinical outcomes and decrease fall rates in the MS population

Characterisation of neural activity across the mouse visual cortex during virtual navigation

The brain’s visual and navigational systems are thought to be involved in distinct neural processes. Yet, it is known that neurons in areas involved in the formation of spatial representations, such as the hippocampus, are also influenced by visual signals. In this Thesis I asked whether a similar influence exists in the opposite direction, namely whether navigational signals influence processing in primary visual cortex (V1) and in six higher visual areas. In parallel, given that little is known about the role of higher visual areas, especially during behaviour, I will seek to characterise their functional properties and differences across conditions of increased behavioural complexity, from passive viewing of drifting gratings all the way to virtual navigation. In the first Results chapter, Chapter 3, I will demonstrate that during running through a virtual reality environment, visual responses as early as in V1 are strongly influenced by spatial position. From Chapter 4 onward, together with V1 I will also focus on 6 higher visual areas (LM, AL, RL, A, AM and PM). Specifically, I will attempt to probe activity in these areas across a wide spectrum of conditions: passive viewing of drifting gratings (Chapter 4); active engagement in virtual reality (Chapter 5) and passive viewing in virtual reality (Chapter 6). The results presented in Chapters 5 and 6 will suggest that spatial modulation is present across visual areas specifically during active behaviour. Finally, in Chapter 7 I will ask whether activity in V1, AL and the posterior parietal cortex (PPC) depends on yet another navigational variable, distance run, and how is this dependence different between areas. In summary, by combining ideas and approaches from research in vision and navigation, I will seek to provide new, intriguing evidence about how neurons across the visual cortex combine visual with navigation-related signals to inform behaviour

Cortical Mechanisms of Visual Target Memory and Movement Planning and Execution for Reaches and Saccades in Humans

The cortical mechanisms for reach have been studied extensively, but directionally selective mechanisms for visuospatial target memory, movement planning, and movement execution have not been clearly differentiated in the human. It is also unclear how effector-specificity evolves in the human brain across these three phases for reaches and saccades. To study these phenomenon, an event-related fMRI design with three key phases was used to break apart a movement into target memory, movement planning and movement execution phases. In the first experimental chapter (chapter 2) directionally selective mechanisms were studied in a memory-guided reach task that informed the subject to perform a pro- or anti-reach after the target memory phase. Using the pro/anti instruction to differentiate visual and motor directional selectivity during planning, we found that one occipital area showed contralateral visual selectivity, whereas a broad constellation of left hemisphere occipital, parietal, and frontal areas showed contralateral movement selectivity. Temporal analysis of these areas through the entire memory-planning sequence revealed early visual selectivity in most areas, followed by movement selectivity in most areas, with all areas showing a stereotypical visuo-movement transition. Cross-correlation of these spatial parameters through time revealed separate spatiotemporally correlated modules for visual input, motor output, and visuo-movement transformations that spanned occipital, parietal, and frontal cortex. In the second experimental chapter (Chapter 3), effector-specific activation for reaches and saccades was studied using a similar design that informed subjects of the effector after the target memory phase. Our analysis revealed more medial (pIPS, mIPS, M1, and PMd) activity during both reach planning and execution, and more lateral (mIPS, AG, and FEF) activity only during saccade execution. These motor activations were bilateral, with a left (contralateral) preference for reach. Apart from right FEF, effector-specific contrasts comparing reach and saccade activation revealed significantly more parietofrontal activation for reaches than saccades during both planning and execution. Cross-correlation of reach, saccade, and reach-saccade activation through time revealed spatiotemporally correlated activation both within and across effectors in each hemisphere, but with higher correlations in the right hemisphere. Taken together, these results demonstrate highly distributed, coordinated occipital-parietal-frontal networks for both reach and saccade, with effector-specific activation

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Adaptive robot body learning and estimation through predictive coding

The predictive functions that permit humans to infer their body state by sensorimotor integration are critical to perform safe interaction in complex environments. These functions are adaptive and robust to non-linear actuators and noisy sensory information. This paper introduces a computational perceptual model based on predictive processing that enables any multisensory robot to learn, infer and update its body configuration when using arbitrary sensors with Gaussian additive noise. The proposed method integrates different sources of information (tactile, visual and proprioceptive) to drive the robot belief to its current body configuration. The motivation is to enable robots with the embodied perception needed for self-calibration and safe physical human-robot interaction. We formulate body learning as obtaining the forward model that encodes the sensor values depending on the body variables, and we solve it by Gaussian process regression. We model body estimation as minimizing the discrepancy between the robot body configuration belief and the observed posterior. We minimize the variational free energy using the sensory prediction errors (sensed vs expected). In order to evaluate the model we test it on a real multisensory robotic arm. We show how different sensor modalities contributions, included as additive errors, improve the refinement of the body estimation and how the system adapts itself to provide the most plausible solution even when injecting strong sensory visuo-tactile perturbations. We further analyse the reliability of the model when different sensor modalities are disabled. This provides grounded evidence about the correctness of the perceptual model and shows how the robot estimates and adjusts its body configuration just by means of sensory information.Comment: Accepted for IEEE International Conference on Intelligent Robots and Systems (IROS 2018

Contextual signals in visual cortex:How sounds, state, and task setting shape how we see

What we see is not always what we get. Even though the light that hits the retina might convey the same images, how visual information is processed and what we eventually do with it depend on many contextual factors. In this thesis, we show in a series of experiments how the sensory processing of the same visual input in the visual cortex of mice is affected by our internal state, movements, other senses and any task we are performing. We found that recurrent activity originating within higher visual areas modulates activity in the primary visual cortex (V1) and selectivity amplifies weak compared to strong sensory-evoked responses. Second, visual stimuli evoked similar early activity in V1, but later activity strongly depended on whether mice were trained to report the visual stimuli, and on the specific task. Specifically, adding a second modality to the task demands extended the temporal window during which V1 was causally involved in visual perception. Third, we report that not only visual stimuli but also sounds led to strong responses in V1, composed of distinct auditory-related and motor-related activity. Finally, we studied the role of Posterior Parietal Cortex in an audiovisual change detection task. Despite extensive single-neuron and population-level encoding of task-relevant visual and auditory stimuli, as well as upcoming behavioral responses, optogenetic inactivation did not affect task performance. Whereas these contextual factors have previously been studied in isolation, we obtain a more integrated understanding of how factors beyond visual information determine what we actually see

The Relationship of Somatosensory Perception and Fine-Force Control in the Adult Human Orofacial System

The orofacial area stands apart from other body systems in that it possesses a unique performance anatomy whereby oral musculature inserts directly into the underlying cutaneous skin, allowing for the generation of complex three-dimensional deformations of the orofacial system. This anatomical substrate provides for the tight temporal synchrony between self-generated cutaneous somatosensation and oromotor control during functional behaviors in this region and provides the necessary feedback needed to learn and maintain skilled orofacial behaviors. The Directions into Velocity of Articulators (DIVA) model highlights the importance of the bidirectional relationship between sensation and production in the orofacial region in children learning speech. This relationship has not been as well-established in the adult orofacial system. The purpose of this observational study was to begin assessing the perception-action relationship in healthy adults and to describe how this relationship may be altered as a function of healthy aging. This study was designed to determine the correspondence between orofacial cutaneous perception using vibrotactile detection thresholds (VDT) and low-level static and dynamic force control tasks in three representative age cohorts. Correlational relationships among measures of somatosensory capacity and low-level skilled orofacial force control were determined for 60 adults (19-84 years). Significant correlational relationships were identified using non-parametric Spearman’s correlations with an alpha at 0.1 between the 5 Hz test probe and several 0.5 N low-level force control assessments in the static and slow ramp-and-hold condition. These findings indicate that as vibrotactile detection thresholds increase (labial sensation decreases), ability to maintain a low-level force endpoint decreases. Group data was analyzed using non-parametric Kruskal-Wallis tests and identified significant differences between the 5 Hz test frequency probe and various 0.5 N skilled force assessments for group variables such as age, pure tone hearing assessments, sex, speech usage and smoking history. Future studies will begin the processing of modeling this complex multivariate relationship in healthy individuals before moving to a disordered population