Tidigare forskning visar att individer med en diagnos inom autismspektrumet (ASD) upplever en större sinneskänslighet vad gäller hörsel, syn och känsel men få studier har undersökt lukt känsligheten. Syftet med föreliggande studie är att få en djupare förståelse för luktfunktioner hos vuxna med ASD.16 deltagare med ASD (14 kontroller) testades i luktkänslighet, fri- och stödd luktidentifiering. Samtliga deltagare självskattade även den upplevda luktkänslighet samt genomgick ett screeningtest för autism, The adult spectrum quotient, AQ. Lukt känslighet, fri och stödd luktidentifikation skiljde sig inte åt mellan de båda grupperna Självskattning av luktfunktioner korrelerade signifikant positivt med AQ poäng vilket visar att personer med högre grad av ASD också upplevde sig som mer luktkänsliga. Föreliggande resultat påvisade att personer med högre AQ-poäng upplevde att de hade en känsligare luktfunktion. Dock reflekterades denna självskattade känslighet inte i de standardiserade lukttesten där inga signifikanta skillnader mellan ASD och kontroller i luktfunktioner påvisades. / Previous research has shown that individuals with a diagnosis within the autism spectrum (ASD) experience a greater sensory sensitivity, but few studies have investigated the olfaction sensitivity. The aim of the present study is to gain a deeper understanding of the olfactory functions in adults with ASD.16 participants with ASD (14 controls) participated in the study where sniffin sticks were used to evaluate the differences between the groups. All participants answered a questionnaire about perceived olfaction sensitivity and the adult spectrum quotient; AQ. Olfactory discrimination and identification (with and without cue) did not differ between the groups, as for olfaction sensitivity, perceived pleasantness, intensity and edibility. When it came to self-assessed olfactory sensitivity, differences were found. However, this self-rated sensitivity did not appear in the standardized odor tests, where no significant differences between ASD and controls odor features were detected.

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.

Cette étude explore les réponses évoquées, l'activité intrinsèque et spontanée de deux populations neuronales différentes dans la région du cerveau correspondant à la patte arrière des souris. Dans cet article, nous nous sommes concentrés sur un modèle murin du syndrome de l'X fragile (SXF), qui est la forme la plus commune de syndrome de retard mental héréditaire et une cause fréquente de troubles du spectre autistique (TSA). SXF est un trouble à gène unique (Fmr1), qui peut être modélisé de manière fiable par un modèle murin transgénique : la souris Fmr1-/y déficiente pour le gène codant Fmr1. L'hyperexcitabilité des réseaux néocorticaux et l'hypersensibilité aux stimuli sensoriels sont des caractéristiques importantes du SXF et des TSA.Ceci est directement lié à un changement du nombre de synapses locales, de canaux ioniques, de l'excitabilité membranaire et de la connectivité des circuits de cellules individuelles. Précédemment, nous avons identifié un défaut dans les canaux ioniques, comme pouvant contribuer à ces phénotypes. Nous avons testé cette hypothèse comme un mécanisme contribuant aux défauts de traitement sensoriel chez les souris Fmr1-/y. Le cortex somatosensoriel primaire de la souris (S1) traite différentes informations sensorielles et constitue la plus grande zone du néocortex, soulignant l'importance de la modalité sensorielle pour le comportement des rongeurs. Nos connaissances concernant le traitement de l'information dans S1 proviennent d'études du cortex en tonneaux lié aux moustaches, mais le traitement des entrées sensorielles des pattes postérieures est mal compris. Par l’utilisation de la technique d’enregistrement de cellule entière par patch clamp in vivo, nous avons classes les cellules en répondeurs supraliminaires (cellules qui répondaient aux stimulations de la patte arrière avec un potentiel d'action), les répondeurs subliminaires (les cellules qui répondaient sans déclencher un potentiel d'action) et les cellules non répondeuses qui ne présentaient aucune réponse. Puis, nous avons comparé les réponses évoquées sub et supraliminaires, les propriétés intrinsèques et l’activité spontanée des neurones pyramidaux de la couche 2/3 (L2/3) de la region S1 de la patte arrière (S1-HP) d’animaux anesthésiés sauvage (WT) et Fmr1-/y. Nous avons identifié des altérations de réponse spontanée, intrinsèque et évoquée chez les souris Fmr1-/y. L’application d’un ouvreur de canaux ioniques BKCa a restauré certaines de ces propriétés altérées chez les souris Fmr1-/y / This study explores the evoked responses, intrinsic and spontaneous activity of two different neuronal populations in the hind paw region of the primary somatosensory cortex (S1) of mice. Initially, we explored information processing in these neurons under normal physiological conditions, and subsequently in a mouse model of Fragile X Syndrome (FXS). FXS is the most common form of inherited mental retardation syndrome and a frequent cause of autism spectrum disorders (ASD). FXS is a single gene (Fmr1) disorder, which can be reliably modeled by a mutant mouse model, the Fmr1 knockout (Fmr1-/y) mouse. Hyperexcitability of neocortical networks and hypersensibility to sensory stimuli are prominent features of FXS and ASD. We previously established a strong causal link between a channelopathy, hyperexcitability of neurons in the primary sensory region of the neocortex and sensory hypersensitivity in this mouse model. In the current study, we extended these findings, by conducting a detailed exploration of the processing of tactile sensory information (evoked by hind paw stimulation) in the neocortex of these mice.Most of our knowledge regarding information processing in S1 comes from studies of the whisker-related barrel cortex (which processes tactile-related sensory information derived from the whiskers), yet the processing of sensory inputs from the hind-paws is poorly understood. Using in vivo whole-cell patch-clamp recordings, we classified the cells into suprathreshold responders (the cells which responded to the hind-paw stimulations with an action potential), subthreshold responders (the cells responded without eliciting an action potential) and non-responder cells (neurons which did not show any response). We then compared the evoked sub- and supra-threshold responses, intrinsic properties, and spontaneous activity of layer (L) 2/3 pyramidal neurons of the S1 hind-paw (S1-HP) region of anaesthetized wild type (WT) and Fmr1-/y mice. We identified spontaneous, intrinsic and evoked response alterations in Fmr1-/y mice. We probed possible mechanisms contributing to this sensory impairment in Fmr1-/y mice. Finally, we tested the possibility of correcting pathophysiological alterations in these neurons using specific pharmacological agents targeting the ion channel defects described previously by our team.