A major challenge in neuroscience is to understand neural coding - how sensory stimuli, or motor actions controlling the behaviour of an animal, are represented by the activity of neurons in the nervous system. Information theory provides a powerful tool for investigating such codes; a rigorous non-parametric theoretical framework for quantifying the properties of noisy communication channels. By viewing various stages of the nervous system as such channels, we can use information theory to obtain meaningful quantitative results about the information capacity of the system, the sensory stimuli or features that are represented, as well as the performance of different candidate codes. In this thesis, we first develop an open source neuroinformatics toolbox implementing robust estimators and bias-corrections for a range of information theoretic quantities. This also includes a novel implementation of an algorithm for numerically obtaining distributions with maximum entropy over discrete probability spaces subject to marginal equality constraints. These maximum entropy distributions provide a powerful tool for investigating the effect of interactions on information transmission by neural population codes. These neuroinformatics tools are then used to explore population coding of the velocity of sinusoidal whisker stimulation in the cortex of anaesthetised rats. We show that both with a pooled model (assuming the neural population is homogenous) and with a labelled line model, interactions are present and affect the information transmission in the system. We show that interactions of order higher than two have a measurable but minor effect on the information capacity of the neural population. This is the first direct quantification of the effect of high order interactions on information transmission in a neural system, and is one of the first studies for which the data lie outside of the perturbative regime in which pairwise models are guaranteed to perform well. We then consider results from a novel experimental preparation, recording from populations in VPm thalamus under both white noise and naturalistic whisker stimulation. We show that sub-millisecond precise spike timing, previously observed with white noise stimuli, is also present with naturalistic stimuli, and that the diverse feature selectivity previously observed across different single unit recording sessions is also present with neurons simultaneously recorded within a single barrelloid. We use a novel information theoretic approach to probe the kinetic selectivity of the recorded cells, showing that they encode combinations of position, velocity and acceleration and that of these, velocity is the best encoded feature. We also quantify the information available to cortex under both a count code and a labelled line code, showing that a simple pooling of the population by a downstream decoder results in a large loss of information, but that this loss may be ameliorated by choosing more carefully the subpopulations over which to pool activity. Finally, we again apply the maximum entropy tools to quantify the effect of interactions, including a novel calculation of the maximal information available to a downstream decoder neglecting correlations of different orders, and find that, similar to the results in cortex, high order correlations do have a measurable effect on information transmission.

Given the dramatic rise in obesity and the diseases linked with it, it is becoming increasingly important to understand the mechanisms that underlie the body's ability to recognize fat. The chemoreception of dietary fat in the oral cavity has largely been attributed to activation of the somatosensory system that relays the textural properties of fat. However, the ability of fatty acids, which are believed to represent the proximate stimulus for fat taste, to activate trigeminal ganglionic neurons has remained unexplored. In general, my research has provided the first evidence of fatty acids activating the somatosensory system by increasing the intracellular calcium concentration and generating receptor potentials. Other experiments were focused on identifying fatty acids-responsive pathways in acute isolated trigeminal neurons involved with fat somatosensory perception. My results revealed that fatty acids-activated pathways involved the release of intracellular calcium stores in subpopulations of trigeminal neurons. By using pseudorabies virus as a "live-cell" tracer, a subpopulation of lingual-innervated trigeminal neurons was labeled. Quantitative real-time polymerase chain reaction on individual neurons showed several transient receptor potential channel markers were expressed in these labeled neurons, which indicated the identification of lingual-innervated neurons was successful. This technique helped resolve the problem of trigeminal neurons being a mixed population of cells, and confirmed the role of the release of intracellular calcium stores in fatty acid-activated pathways. Using patch clamp recording, I discovered that the linoleic acid activated signaling pathway involved the activation of G protein and phospholipase C. I further began to characterize the downstream conductance that is activated by linoleic acid in rat trigeminal neurons. Using perforated patch clamp recording, I have recorded linoleic acid-induced currents that exhibited many of the properties of transient receptor potential-like channels, suggesting that this "cellular sensor" is probably playing an important role in the somatosensory perception of fat. Taken together, this dissertation research has revealed the ability of fatty acids to act as effective tactile stimuli and identified several elements of the fatty acids-activated signaling pathway involved in the somatosensory perception of fat.

The effect of refractive blur upon postural stability was investigated under three conditions: normal standing, standing with input from the somatosensory system disrupted and standing with input from the somatosensory and vestibular systems disrupted. Standing stability was assessed using the centre of pressure (COP) signal from force plate data in four young subjects (mean 23.9 ± 3.1 years) and five repeated sets of measurements were taken. The subjects looked straight ahead at a horizontal and vertical square wave pattern of 2.5 cycles (degree)¿1. Under each of the three test conditions, standing stability was measured with the optimal refractive correction and under binocular blur levels of 0, + 1, + 2, + 4, and + 8 D and with eyes closed. In the normal standing condition, dioptric blur had only a mild effect on postural stability. However refractive blur produced large increases in postural instability when input from one or both of the other two sensory systems were disrupted. We hypothesized that dioptric blur would have an even great effect on postural stability if the visual target used was of higher spatial frequency. This was confirmed by repeated measurements on one subject using a target of 8 cycles (degree)¿1. The study highlights the possible importance of an optimal correction to postural stability, particular in situations (or people) where input from the somatosensory and/or vestibular systems are disrupted, and where the visual surrounds are of high spatial frequency.

This essay is about the somatosensory system, which is divided into different kinds of touch. Described briefly are the proprioceptive touch, which is transported to the brain via A-alfa fibers and transmits information about e. g. limb position and movement. The cutaneous touch is the main focus and it is divided into discriminative touch and affective touch. The first corresponds to stimuli such as vibration and pressure and is transported via A-beta axons. The second, affective touch, corresponds to e.g. painful and pleasant stimuli which are transported to the brain via A-delta and C-fibers. The aim of the essay is to give an overview of the sense of touch, by doing a literature search, including a discussion of relevant neuronal correlates focusing particularly on affective touch. Moreover, the physiological aspects of touch will be presented. The sources that are used are review and original articles taken from databases such as ScienceDirect, and some articles send by the author. Some books have also been used to find more general knowledge. The conclusion for the essay is that touch is important for humans to function in everyday life. Additional, a specific receptor called C- tactile (CT) is identified to correspond to gentle touch and is suggested to have a vital role for humans in maintaining and forming social bounds. Moreover, discriminative touch is associated with activation in the primary and secondary somatosensory cortex, whereas affective touch seems to be associated with activity in the orbitofrontal cortex, cingulate cortex and the insula cortex, as well as the prefrontal cortex, which is suggested to be activated during interpersonal touch. Further, the sense touch needs to be more researched in order to understand its functions and benefits deeper.

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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22828号 / 医博第4667号 / 新制||医||1047(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 古川 壽亮, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

ABSTRACT Whiplash associated disorders (WAD) is one of the most debated musculoskeletal conditions. Sensory disturbances including hypersensitive responses to mechanical, thermal and electrical stimulation have been consistently shown to be a feature of both the acute and chronic stages of the whiplash condition. More importantly, such dysfunctions have also been found to be associated with higher risk of poor functional recovery. It is apparent that better understanding of the sensory disturbances in WAD is needed in order to elucidate mechanisms underlying the pain and disability of this recalcitrant condition and to facilitate the development of more effective management strategies. Comprehensive Quantitative Sensory Testing (QST) combining sensory detection and pain threshold measures is proving to be a valuable tool to advance the classification and illuminating the underlying mechanisms of an array of musculoskeletal pain disorders but such protocol has never been undertaken in a WAD cohort. In order to fill this gap in knowledge, the series of studies in the thesis aimed to utilize comprehensive QST to investigate the presence of somatosensory dysfunction in chronic WAD and to compare the somatosensory profile of WAD to cervical radiculopathy and idiopathic (non-traumatic) neck pain. Once a better understanding of the potential underlying mechanisms in chronic WAD was established, the research then focused on documenting the presence of such somatosensory disturbances soon after whiplash injury and its temporal development over a 6 months period. The results have provided a number of significant insights into some of the potential underlying mechanisms of the somatosensory dysfunction in WAD as well as other neck pain conditions of different aetiology. It is clear that generalised sensory hypoaesthesia coexisted with sensory hypersensitivity in chronic WAD and a combination of pain and detection measures best discriminated patients with WAD and controls. Similar sensory presentation was also found in patients with cervical radiculopathy but not in idiopathic neck pain patients. This finding indicates that different mechanisms underlie various musculoskeletal conditions with disordered central processes contributing to a greater degree in some conditions. Patients with whiplash and those with cervical radiculopthy may share similar underlying pain mechanisms involving the central nervous system and the discrepant findings in the idiopathic neck pain group may be due to the magnitude of nociceptive input required to induce/maintain altered central adaptive changes. Another important observation from the studies was that sensory hypoaesthesia was present in the majority of patients with whiplash injury in the acute stage. However, it persisted only in individuals who initially reported higher levels of pain and disability levels and sign of hypersensitivity. It was this group of individuals who predominantly developed persistent symptoms at six months post injury. The longitudinal findings indicate that such sensory impairments can be identified very early on and treatment interventions directed at these sensory disturbances (both sensory hypersensitivity and hypoaesthesia) should aim to reduce the nociceptive input and this may improve recovery post whiplash injury. The findings in this thesis demonstrated the clear association between sensory hypersensitivity and other sensory disturbances and their potential influence on recovery. Furthermore, the heterogeneity of the whiplash condition highlighted the importance of the early identification of “low-risk and “high-risk” patients in order to assist the clinicians to make clinical decisions on the best management approach. It cannot be overemphasised that the early assessment of whiplash injured patients should aim to identify features associated with poor recovery and a better classification system will be an important step. Implications for assessment and management of whiplash are vital in the acute stage of injury and may well go some way toward preventing the transition to chronicity, particularly in those with a more complex clinical presentation involving somatosensory disturbances. Further research directions have also been identified in order to improvement management of this complex clinical condition.

Title: 3D analysis of immediate effect on posture of shoe with postural insoles based on Rašev and with proceptor insoles PodoAktiv® Objectives: The thesis aims to show the immediate effect of application of custom-made insole on postural hold of chosen body segments and we would like to determine whether it is possible to use PodoAktiv® or insole based on Rašev to correct body posture. Methodology: In this thesis we examined 9 participants who agreed joining the study. We used the Balance®4D device made by Paromed company. The selected body segments were marked by white spheric stickers. To compare postural hold of selected body segments we examined the participants in altogether 4 situations. Barefoot stand, stand in shoes without insoles, stand in shoes with postural insoles based on Rašev and stand in shoes with proceptor insoles PodoAktiv®. Results: The results of this study show that there is a slight immeadiate effect of the custom- made insoles on postural hold of body segments. Larger effect was observed in the participants who already had a bad postural barefoot hold. Of all 6 parameters, the biggest effect was observed in the shift of overall body axis after application of PodoAktiv® insoles. Keywords: Shoe insoles, proprioceptors, somatosensory system, 3D static analysis, postural hold

Fascial tissues form a continuous whole-body three-dimensional network penetrating all parts of the human body. They include all fibrous connective tissue that significantly contributes both to themaintaining of the integrity of the organism and the functioning of body systems and the somesthetic perception.That is because of the facia is richly populated by proprioceptiveand mechanosensitive nociceptive nerve endings. Although the stretching is a routine method used in sports and rehabilitation, its exact mechanism of influence and effects on the body are not fully understood so far. Stretching exercises affect the mechanical state of the myofascial tissues and also the quality of the nociception and proprioception by alteration of their preload. There is evidence about some differences of the mechanical properties of the tissuesboth between thesexes and hypermobile individuals. The theses assesses the effect of static stretching m. QF on the somesthetic perception by measuring pressure pain threshold (PPT) using pressure algometry and the quality of propcioception bygoniometric measurement considering the interindividual variance in quality of the connective tissues. Our research includes testing of 29 healthy subjects (14 women and 15 men) and it has proved significant impact of the intervention on the...

OF DIPLOMA THESIS Name and surname: Bc. Lia Medková Thesis supervisor: MUDr. Yvona Angerová, Ph. D., MBA Referee: Title thesis: The effect of sensation disorders on upper limb function in patients after brain injury Abstract The aim of this thesis was to determine The effect of sensation disorders on upper limb function in patients after brain injury. Method: The research for this thesis involved non-experimental pre-research and quasiexperiments. The thesis' theoretical hypothesis was developed on the basis of previous studies that had looked at the effect of brain damage on patients' upper limb function. A total of twenty patients between the ages of 20 - 59 were selected to participate in the empirical study reported in this thesis. All participating patients had suffered damage to their cerebral cortex. The causes of their brain damage included strokes, trauma and tumor. The participants were divided into two groups of ten using the Nottingham Sensory Assessment. Participants with sensory disorders were allocated to the experimental group. Participants without sensory disorders were placed in the control group. The Jebsen-Taylor test was performed on all participants to assess their upper limb function after they had suffered brain damage. Results: Hypothesis thesis: Disorders of superficial,...