Background Individuals with Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), and stroke experience various cognitive and motor impairments, which can negatively affect their ability to complete daily activities such as walking and talking. Walking and talking or dual-task walking often leads to a decline in performance in one or both tasks, which is called dual-task cost. This dual-task cost seems to be more pronounced in individuals with neurological conditions compared to age-matched healthy individuals, possibly due to disease-associated impairments. While the results of neuroimaging studies are inconsistent, several studies have found structural or functional brain changes that might contribute to a decrease in dual-task walking performance in people with neurological disorders. Research question/objective The objective of this study was to systematically review peer-reviewed articles that examined the neural correlates of cognitive-motor dual-task interference in people with neurological conditions. The primary aim was to identify brain areas or measures that might underlie dual-task walking performance of people with MS, stroke, AD, and PD. The secondary aim was to compare their dual-task performance with other groups such as healthy individuals. Methods A systematic review of the literature was conducted, following PRISMA guidelines, on Medline, Embase, and Scopus databases. Studies were included if they examined dual-task walking performance and associated structural or functional brain changes in adults with stroke, MS, PD, and AD. Studies were first screened using a title and abstract and then full-text review was performed. The quality of each study was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist and then the data regarding cognitive and motor performance during dual- versus single task conditions and brain imaging were extracted. The findings were grouped according to neurological condition and then by imaging technique. Results After screening, 23 studies were selected to be included in this review. The majority (90%) showed a decline in dual-task walking performance compared to single-walking in people with neurological conditions and this decline was greater than healthy individuals. Most structural imaging studies (75%) reported a significant positive correlation between lower brain structural integrity and poorer dual-task walking performance. Specifically, the striatum regions including pedunculopontine nucleus and hippocampus in PD demonstrated this positive correlation. In MS, the supplementary motor area showed a positive correlation. In terms of functional brain changes, 60% observed an increase in prefrontal cortex activity during dual tasking in people with PD and stroke, which was associated with decreased performance in most cases (n = 3) while some found an association with maintained performance (n = 2). Further, people with MS and stroke both showed a significant relationship between a higher supplementary motor area activity and poor dual-task walking performance. Conclusions This systematic review identified several structural and functional neural correlates of dual-task walking in people with PD, MS, and stroke and has facilitated a better understanding of neural basis of dual-task interference in people with neurological conditions. However, the relationship between the brain and behavioural outcomes is complicated and various factors may influence neural correlates, such as individuals’ characteristics (e.g., neural reserve, age), the nature of cognitive task used, and presentation modality (e.g., visual).

Introduction: Obsessive-compulsive disorder (OCD) is a complex disorder that is associated with significantly impaired functioning. The current prevailing model of OCD implicates dysfunction of the serotonergic neurotransmitter system and fronto-striatal neural networks, but challenges in replicating findings within OCD samples are often attributed to clinical heterogeneity. OCD symptoms that develop or worsen within the perinatal period appears to reflect a distinct subtype of the disorder, but the genetic and neurobiological factors that contributes to its presentation in women is poorly understood. In this dissertation, we aimed to review the literature on the genetic architecture of OCD, identify potential gene candidates for perinatal OCD and analyze one serotonin system gene according to OCD and possible subtypes using meta-analytic techniques. Based on these findings, we then tested the association of serotonergic candidate gene polymorphisms with the presence of infant-related obsessive-compulsive symptoms (OCS). Lastly, we investigated the cortical morphological features associated with perinatal OCD and OCS symptom severity in postpartum mothers. Results: From prior reports in the literature and our own meta-analytic investigation, polymorphic variants in genes coding for the serotonergic transporter and serotonin 2A receptor subtype (SLC6A4 and HTR2A, respectively) appear to be candidates for perinatal OCD due to their association in female samples. However, upon investigation in our perinatal sample (n=107), we found no evidence to support the association of the 5-HTTLPR polymorphism of SLC6A4 with perinatal-related OCS, but larger samples are needed to confirm this finding. Due to technical challenges, the HTR2A polymorphism remains to be tested. Our novel whole-brain explorations revealed distinct cortical morphology associated with symptom worsening across the perinatal period, irrespective of diagnosis. Cortical parameters were not able to differentiate mothers with and without OCD; however, OCD mothers displayed positive correlations between cortical surface area and symptom severity in widespread regions, including the frontal, parietal, temporal and occipital cortex. Conclusions: Overall, this body of work aimed to fill the gap in the literature by exploring the possible genetic and cortical correlates of perinatal-related OCS and OCD. While 5-HTTLPR or HTR2A are candidates for perinatal OCD, it is not yet clear whether they increase susceptibility for the development of infant-related OCS in the perinatal period. Distinct cortical alterations in surface area appeared alongside OCS exacerbation in the postpartum period in regions that extend beyond the frontoparietal network. This suggests that additional neural networks may be contributing to symptom severity and that the cortical plasticity that occurs across the perinatal period may predispose women for risk of OCD. Future studies should continue to use a multiple perspective approach, that utilizes genetic and neurobiological techniques, in order to provide greater insight into the etiology of perinatal OCD. / Dissertation / Doctor of Philosophy (PhD) / Women are at greater risk for the development of mental illness in the time surrounding pregnancy and postpartum, known as the perinatal period. In the case of perinatal obsessive-compulsive disorder (OCD), mothers may experience unique worries in regard to their parenting or fears that their baby may be harmed. While these worries are common, they can become disruptive when persistent and impact the mother’s mood and ability to bond with the infant. Our current understanding of OCD includes the influence of genetic factors and brain changes, but little is understood about what factors may increase risk for OCD in the perinatal period. In this thesis, we aimed to review whether certain alterations within DNA segments, known as gene variants, may be linked to the development of OCD in females and if these gene changes, as well as differences in brain structures in postpartum mothers, are associated with OCD symptoms during the perinatal period. The genes we examined are important for regulating a chemical signaling substance in the brain known as serotonin. Based on our results, we did not find a relationship between serotonin gene variants and OCD symptoms in perinatal women. We also found no differences when comparing the cortical brain structures between mothers with OCD and healthy mothers; however, we observed that measures of surface area across several cortical brain regions were related to symptom worsening from pregnancy to postpartum, and also with symptom severity in postpartum mothers with OCD. These results suggest that there are widespread brain changes during the postpartum period that may increase a mother’s risk for developing OCD. Overall, the work in this thesis provides the first glimpse into potential risk factors for perinatal OCD.

Impulsivität ist ein zentraler Aspekt der Persönlichkeit, welcher entlang eines Kontinuums in normaler bis devianter Ausprägung auftreten kann. So moduliert persönlichkeitsbezogene Impulsivität sowohl das Verhalten Gesunder, als auch, in ihrer extremen Ausprägung, klinisch relevante Verhaltensweisen. Signifikant überdurchschnittlich ausgeprägte Impulsivität gilt als charakteristisch für eine Vielzahl psychiatrischer Krankheitsbilder wie Abhängigkeitserkrankungen. Die differentiell-psychologische Forschung geht von einer Persönlichkeitseigenschaft aus, welche den verschiedenen Facetten des Phänomens Impulsivität zu Grunde liegt. Jedoch sind strukturelle Bildgebungsstudien an gesunden Probanden zu diesem Gegenstand noch immer rar und ihre Befunde sehr heterogen. Ziel der vorliegenden publikationsbasierten Dissertationsschrift ist es, einen Beitrag zu einem vertieften Verständnis zerebraler struktureller Korrelate persönlichkeitsbezogener Impulsivität bei Gesunden zu leisten. In drei empirischen Untersuchungen wurden Daten struktureller Magnetresonanztomographie bei Gesunden erhoben und jeweils auf korrelative Zusammenhänge mit persönlichkeitsbezogener Impulsivität getestet. Insgesamt zeigten die für multiple Testung korrigierten Ergebnisse dieser Arbeit negative Korrelationen zwischen persönlichkeitsbezogener Impulsivität und morphometrischen Maßen (kortikale Dicke, kortikales Volumen) des linken superior frontalen Kortex, des linken mittleren frontalen Kortex sowie des linken orbitofrontalen Kortex. Erstmalig wurden Zusammenhänge zwischen Impulsivität als spezifischer Persönlichkeitsfacette und der Kortexdicke an einer repräsentativen gesunden Stichprobe gezeigt. Insgesamt weisen die Ergebnisse auf eine zentrale Rolle linkshemisphärischer Strukturen im Bereich des präfrontalen Kortex für Impulsivität hin. / Impulsiveness is a pivotal aspect of personality comprising a continuum from normal to deviant occurrence. Trait impulsiveness modulates both behavior in healthy individuals and, in its extreme occurrence, even clinically relevant behavior. So, inhibition disorder is understood to be a characteristic in a number of mental health problems such as addiction disorders, personality disorders and attention deficit/ hyperactivity disorders. Research in the field of personality psychology views impulsiveness as a broad trait underlying all of the different facets of impulsiveness. The interest in the biological correlates of trait impulsiveness has stimulated a growing number of neuroscientific studies. However, non-clinical structural imaging studies on impulsiveness are still rare and their findings very heterogeneous. The present cumulative thesis aims to contribute to an advanced understanding of structural cerebral correlates of trait impulsiveness in healthy individuals. Within the scope of three empirical studies structural data were acquired by means of high-resolution magnetic resonance scans in healthy participants and tested respectively for correlations with trait impulsiveness. Summarizing these present studies’ findings, the results surviving a multiple comparison corrected threshold showed negative correlations between trait impulsiveness and morphometric measurements (cortical thickness, cortical volume) of the left superior frontal cortex, the left middle frontal cortex and the left orbitofrontal cortex. For the first time, associations between impulsiveness as a certain facet of personality and cortical thickness have been shown in a representative healthy sample. The present work provides further insight into structural cerebral substrates of trait impulsiveness considering novel methodological aspects. In summary, the results suggest structures of the left prefrontal cortex play a central role in impulsiveness.

Cette thèse a pour objectif l’investigation du circuit des récompenses, sur les plans comportementaux et neuronaux, chez des adolescents à risque parental élevé de dépression majeure et de trouble bipolaire, en comparaison à des jeunes à risque parental peu élevé. Plus précisément, le but est d’identifier des marqueurs comportementaux et neuronaux du risque de développer une dépression majeure ou un trouble bipolaire, afin d’être en mesure de détecter et de prévenir ces troubles le plus tôt possible pour éviter, ou du moins retarder, leur émergence. Pour ce faire, nous avons réalisé deux études, présentées ici dans deux articles empiriques. Dans le premier article, le fonctionnement comportemental et neuronal du circuit des récompenses a été investigué au moyen d’une tâche d’anticipation et d’obtention de gains et de pertes monétaires, chez des adolescents à risque parental de dépression majeure (i.e., jeunes asymptomatiques dont un des parents souffre de dépression majeure), des adolescents à risque parental de trouble bipolaire (i.e., jeunes asymptomatiques dont un des parents souffre de trouble bipolaire) et des adolescents contrôles (i.e., jeunes asymptomatiques dont les deux parents sont en bonne santé mentale). Au niveau comportemental, les résultats ont révélé une meilleure performance chez les jeunes à risque de dépression majeure lorsqu’ils devaient éviter d’obtenir des pertes monétaires de magnitude variée (0,20$, 1$ ou 5$), ainsi qu’une meilleure performance chez les jeunes à risque de trouble bipolaire sur les essais impliquant d’éviter des pertes monétaires de magnitude nulle (0$). Au niveau neuronal, les jeunes à risque de dépression majeure démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude variée, tandis que les jeunes à risque de trouble bipolaire démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude nulle. De plus, les jeunes à risque de dépression majeure tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal durant l’évitement réussi de pertes monétaires, tandis que les jeunes à risque de trouble bipolaire tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal lors de l’obtention de pertes monétaires. Dans le deuxième article, l’intégrité structurelle des régions fronto-limbiques a été investiguée, au moyen de mesures du volume, de l’épaisseur corticale et de la superficie corticale. Les résultats ont mis en évidence, chez les jeunes à risque de trouble bipolaire, un volume plus élevé du cortex préfrontal dorsolatéral, par rapport aux jeunes à risque de dépression majeure et contrôles. De plus, les jeunes à risque de trouble bipolaire présentaient un volume plus élevé du cortex cingulaire postérieur, en comparaison aux jeunes à risque de dépression majeure. Enfin, une diminution de l’épaisseur corticale du cortex orbitofrontal et du gyrus frontal moyen a été observée chez les adolescents à risque de trouble bipolaire, en comparaison au groupe contrôle. L’ensemble de ces résultats démontre ainsi l’existence de particularités comportementales et d’altérations neuronales sur les plans fonctionnel et structurel, chez des jeunes à risque élevé de troubles de l’humeur, et ce, avant même l’émergence des premiers symptômes thymiques. Plus particulièrement, ces caractéristiques pourraient constituer des marqueurs du risque de développer un trouble de l’humeur. Par conséquent, ces marqueurs pourraient aider à mieux identifier les jeunes qui sont le plus à risque de développer un trouble de l’humeur, et ainsi permettre la mise en place précoce de stratégies préventives adaptées, afin d’éviter des trajectoires développementales psychopathologiques. / This thesis aims to investigate the behavioral and neural reward circuitry, in youths at high parental risk for major depressive and bipolar disorder, in comparison to youths at low parental risk for mood disorders. More specifically, the goal is to identify behavioral and neural markers of the risk to develop a major depressive or a bipolar disorder in order to early detect and prevent these disorders, and ultimately to avoid, or at least delay, their emergence. To do so, we conducted two experiments, presented herein in two empirical articles. In the first article, behavioral and neuronal reward circuitry were investigated in youths at high parental risk for major depressive disorder (i.e, asymptomatic youths which one of the parents is suffering from major depression), youths at high parental risk for bipolar disorder (i.e, asymptomatic youths which one of the parents is suffering from bipolar disorder) and control youths (i.e, asymptomatic youths from mentally healthy parents). Therefore, we used a monetary incentive delay task allowing the assessment of monetary gain and loss anticipation and outcome. Behaviorally, results revealed a better performance in youths at risk for major depressive disorder on trials involving potential losses of various magnitude (0,20$, 1$ or 5$), as well as a better performance in youths at risk for bipolar disorder on trials involving potential null losses (0$). Regarding imaging data, youths at risk for major depressive disorder demonstrated a reduced activity in the dorsolateral prefrontal cortex during the anticipation of potential monetary losses of various magnitude, while youths at risk for bipolar disorder showed a reduced activity in the dorsolateral prefrontal cortex during the anticipation of potential null losses. Moreover, youths at risk for major depressive disorder tended to have an increased activity in the orbitofrontal cortex during successful avoidance of monetary losses, while youths at risk for bipolar disorder tended to demonstrate an increased activity in the orbitofrontal cortex during feedback of monetary losses. In the second article, structural integrity of fronto-limbic regions was investigated, through volumetric, cortical thickness and surface area measures. Results have highlighted, in youths at risk for bipolar disorder, an increased volume in the dorsolateral prefrontal cortex, compared to both youths at risk for major depressive disorder and controls. Moreover, youths at risk for bipolar disorder showed an increased volume in the posterior cingulate cortex, in comparison to youths at risk for major depressive disorder. Finally, a reduced thickness in the orbitofrontal cortex and middle frontal gyrus were observed in youths at risk for bipolar disorder, in comparison to control youths. Taken together, these results demonstrate the existence of behavioral particularities, and neuronal alterations regarding functional and structural data, in youths at high risk for mood disorders, and this, even before the emergence of the first mood symptoms. More specifically, these characteristics might constitute markers of the risk to develop a mood disorder. Consequently, these markers could help to better identify youths who are most at risk to develop a mood disorder, and thus allow the early implementation of adapted preventive strategies to avoid psychopathological developmental trajectories.

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