In a series of studies, lifestyle activities, mental health and aerobic fitness were investigated in relation to mean RT and response time variability (trial-to-trial variability in RT performance) obtained from a battery of cognitive measures in 257 healthy adults aged 50 to 90 years (M = 63.60). Cognition was assessed across four domains; psychomotor performance, executive function, visual search and word recognition. Hierarchical multiple regression analyses and structural equation modelling (SEM) were used to explore associations between age and outcome measures in a mediated-moderator analysis. The dedifferentiation of cognition and the dissociation between the outcome measures of mean RT and response time variability was also explored. Additionally, the neural correlates of response time variability were investigated using functional magnetic resonance imaging (fMRI). The findings indicated that poor mental health was associated with greater within-person (WP) variability and slower mean RTs and that this effect was greater in older adults. Higher lifestyle activity scores and higher aerobic fitness (VO2max) attenuated negative age gradients in WP variability and mean RT. Analyses suggested that the above effects were mediated by executive function. There was no evidence of dedifferentiation across cognitive domains and there was selective dissociation between the measures of mean RT and WP variability. The fMRI results suggested that WP variability was associated with fluctuations in executive control and, relatedly, attentional lapses. Overall, the findings suggest that executive function mediates a substantial portion of age-related variance in cognition and that this association is influenced by moderators such as an active lifestyle, aerobic fitness and mental health. The findings underline the potential benefits and importance of interventions to help maintain and promote mental health, and active lifestyles, in old age.

With an estimated prevalence of ~1%, Autism Spectrum Disorder (ASD) is relatively common. Whilst accepted as a neurodevelopmental disorder, currently the diagnosis of autism is based on the observation of characteristic behaviour: deficits in language, communication and social skills in addition to unusual or restricted interests. Research in the condition has been approached with psychological and physiological methodology however a full understanding of the underlying neuropathology of autism is still unclear. Functional Magnetic Resonance Imaging (fMRI) has been employed to study face processing in ASD with varied results. The processing of other types of social cues has been far less extensively explored and similarly, whilst there have been some reports of aberrant neural responsiveness to emotion in ASD, this component of social cognition requires further study. In particular, it is unclear whether there is a specific deficit in processing faces in ASD or rather a global deficit in emotion processing which is present across stimulus types, sensory domains and emotions. In this study basic emotion labelling using a range of stimulus types has been investigated within the same ASD cohort. In comparison to a control group, deficits were apparent in the ASD group when processing emotion in face, whole body and voice stimuli. This indicates a global emotion processing deficit in ASD that cannot be fully accounted for by deficits in basic face processing alone. Processing neutral and emotional faces and static whole body images was subsequently investigated using fMRI. When neutral faces, neutral bodies, fearful faces and fearful bodies were contrasted with fixation baseline, both groups broadly recruited the expected network of brain regions. When the emotional condition was contrasted with the neutral condition for each stimulus type significant between groups differences were apparent. The bilateral inferior parietal lobe responded significantly differently in response to facial emotion and the right supplementary motor area and superior temporal sulcus region was differentially activated in response to emotion in body stimuli. Findings reported here suggest that there are wide ranging social deficits in ASD which relate to the processing of a variety of social cues. fMRI evidence suggests that these deficits have a neural basis, in which elements of the social brain, including regions associated with mirror neuron function, activate in an atypical manner in ASD.

School-mathematics has been shown to mainly comprise rote-learning of procedures where the considerations of intrinsic mathematical properties are scarce. At the same time theories and syllabi emphasize competencies like problem solving and reasoning. This thesis will therefore concern how task design can influence the reasoning that students apply when solving tasks, and how the reasoning during practice is associated to students’ results, cognitive capacity, and brain activity. In studies 1-3, we examine the efficiency of different types of reasoning (i.e., algorithmic reasoning (AR) or creative mathematically founded reasoning (CMR)) in between-groups designs. We use mathematics grade, gender, and cognitive capacity as matching variables to get similar groups. We let the groups practice 14 different solution methods with tasks designed to promote either AR or CMR, and after one week the students are tested on the practiced solution methods. In study 3 the students did the test in and fMRI-scanner to study if the differing practice would yield any lasting differences in brain activation. Study 4 had a different approach and focused details in students’ reasoning when working on teacher constructed tasks in an ordinary classroom environment. Here we utilized audio-recordings of students’ solving tasks, together with interviews with teachers and students to unravel the reasoning sequences that students embark on. The turning points where the students switch subtask and the reasoning between these points were characterized and visualized. The behavioral results suggest that CMR is more efficient than AR, and also less dependent on cognitive capacity during the test. The latter is confirmed by fMRI, which showed that AR had higher activation than CMR in areas connected to memory retrieval and working memory. The behavioral result also suggested that CMR is more beneficial for cognitively less proficient students than for the high achievers. Also, task design is essential for both students’ choice of reasoning and task progression. The findings suggest that: 1) since CMR is more efficient than AR, students need to encounter more CMR, both during task solving and in teacher presentation, 2) cognitive capacity is important but depending on task design, cognitive strain will be more or less high during test situations, 3) although AR-tasks does not prohibit the use of CMR they make it less likely to occur. Since CMR-tasks can emphasize important mathematical properties, are more efficient than AR- tasks, and more beneficial for less cognitively proficient students, promoting CMR can be essential if we want students to become mathematically literate.

We used fMRI to examine the neural substrates of sublexical phoneme-grapheme conversion during spelling in a group of healthy young adults. Participants performed a writing-to-dictation task involving irregular words (e.g., choir), plausible nonwords (e.g., kroid), and a control task of drawing familiar geometric shapes (e.g., squares). Written production of both irregular words and nonwords engaged a left hemisphere perisylvian network associated with reading/spelling and phonological processing skills. Effects of lexicality, manifested by increased activation during nonword relative to irregular word spelling, were noted in anterior perisylvian regions (posterior inferior frontal gyrus/operculum/precentral gyrus/insula), and in left ventral occipito-temporal cortex. In addition to enhanced neural responses within domain-specific components of the language network, the increased cognitive demands associated with spelling nonwords engaged domain-general frontoparietal cortical networks involved in selective attention and executive control. These results elucidate the neural substrates of sublexical processing during written language production and complement lesion-deficit correlation studies of phonological agraphia.

Eating unhealthy foods and eating past satiety are inappropriate behaviors that promote obesity. The ability to effectively inhibit an inappropriate behavior is a key component of cognitive restraint and its impairment has been previously linked to obesity. In this study, a Go/No-Go fMRI task was completed by a cohort of adult women that had experienced initial weight loss followed by various levels of weight regain or continued weight loss. Region of interest fMRI analysis revealed that greater total weight loss was significantly related to decreasing activation in the right inferior frontal gyrus and the right superior frontal gyrus. These results suggest that as weight loss increases fewer cognitive resources are needed in order to maintain levels of inhibitory control. This cognitive efficiency, though only partially supported by better task performance, is supported by greater exercise. An analysis of resting state patterns of correlation between task-activated regions revealed a significant correlation between the right inferior frontal gyrus and the left middle temporal gyrus. The strength of this relationship was significantly correlated with increasing total weight loss and continued weight loss over time. Cognitive restraint was also associated with this fronto-temporal correlation and provides support for cognitive efficiency. Right inferior frontal gyrus was also correlated with left inferior frontal gyrus and this relationship was positively correlated with initial weight loss suggesting that fewer neurocognitive resources were required by those who were able to achieve greater initial weight loss.

Women have greater incidence and prevalence of Major Depressive Disorder (MDD) than men during the reproductive life phase when ovarian hormones fluctuate, suggesting that ovarian hormones have a significant role in MDD etiology in women. As the core symptoms of MDD are indicative of alterations in stress responding, emotional processing, and mood regulation, examining the effects of the estrogen on these processes in women may provide a better understanding of the role of estrogen in the sex difference in MDD rates. The general aim of this dissertation was to examine neural, emotional, and attentional processes related to stress response alterations and cognitive bias in MDD in women. To examine menstrual phase and estradiol level effects on the neural and mood response to psychosocial stress, healthy, normally cycling women were examined at either the high or low estradiol phase of the menstrual cycle. Participants were exposed to the Montreal Imaging Stress Task (MIST), with brain activity measured through functional magnetic resonance imaging (fMRI), and behavioral response assessed with subjective mood and stress measures. We found that women during the high estradiol phase showed significantly less hippocampal deactivation during psychosocial stress compared to women during the low estradiol phase. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. These results suggest that high estradiol may be protective against the shifts in brain system activity and negative mood responses associated with psychosocial stress. Periods of low estradiol may enhance the negative impact of psychosocial stress on neural activity and mood and thus contribute to MDD risk in vulnerable women. The relation of cognitive bias to depression history in women was examined in postmenopausal women with and without a history of major depression using an emotion dot probe task during fMRI. Women with remitted MDD showed greater attentional facilitation for negative images than women with no history of MDD that was directly correlated with amygdala activity for negative images and amygdala-hippocampal connectivity in a resting scan. These findings provide evidence that differences in activity and functional connectivity in emotional processing networks may provide a neurobiological basis for continued cognitive bias in remitted MDD. Preliminary data indicate that estradiol treatment reduces amygdala-hippocampal connectivity specifically in women with a history of MDD and has interactive effects with MDD history on the mood response to psychosocial stress following the MIST such that women with a history of MDD appear to benefit from estradiol treatment while women without such history do not. Women with a history of or vulnerability to MDD may be particularly sensitive to the positive effects of estradiol on brain systems important to regulating emotional responses to psychosocial stress. The findings presented in this dissertation suggest that estrogen fluctuations across the menstrual cycle and at other reproductive events may contribute to depression risk through effects on brain systems integral to emotional evaluation and response with potential cognitive consequences.

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task particularly in olfactory Functional MRI studies due to the factors such as (a) susceptibility-induced signal loss in olfactory related brain areas and (b) desensitization to odors due to prolonged odor stimulation, which is typical when block paradigms are used. Therefore, when block paradigms are used in olfactory interventional Functional MRI studies, the effect of the intervention may not be easily interpretable due to the factors mentioned above. The first task of this thesis was to select a block stimulation paradigm that would produce a large and reproducible BOLD response. It was hypothesized that a BOLD response of this nature could be produced if within-block and across-session desensitization could be minimized and further, that desensitization could be minimized by reducing the amount of odor by pulsing the odor stimulus within a block instead of providing a continuous odor throughout the block duration. Once the best paradigm was selected, the second task of the thesis was to select the best model for use in general linear model (GLM) analysis of the functional data, so that robust activation is detected in olfactory related brain areas. Finally, the third task was to apply the paradigm and model that were selected as the best among the ones tested in this thesis, to an olfactory interventional Functional MRI study investigating the effect of food (bananas) eaten to satiety on the brain activation to the odor related to that food. The methods used in this thesis to ensure valid interpretation of an interventional effect, can serve as a template for the experimental design of future interventional Functional MRI studies.

La compréhension du fonctionnement cérébral est en constante évolution depuis l’essor des neurosciences.Les nouvelles modalités d’imagerie ont permis de mettre en évidence une architecture de notre cerveau en réseaux complexes. Mon travail a pour but de développer une méthode mettant en évidence les réseaux les plus représentatifs d’un groupe de sujet en IRM fonctionnelle.Dans un premier temps, j’ai développé une méthode de réduction des données basées sur le clustering.J’ai introduit une nouvelle caractérisation de l’information fonctionnelle par le profil de connectivité.Celui-ci permet de réduire le biais induit par le bruit présent au sein des données d’IRM fonctionnelle.De plus ce profil ne nécessite pas d’a priori sur les données contrairement aux méthodesi nférentielles classiques.Dans un deuxième temps, j’ai développé une méthode qui permet l’identification de réseaux communs sur un groupe de sujets tout en prenant en compte les variabilités spatiales et fonctionnelles inter-sujets. Les réseaux obtenus peuvent ensuite être caractérisés par leur distribution spatiale mais également par les liens de connectivités se manisfestant en leur sein.Cette méthode permet également la comparaison des réseaux de différents groupes de sujets et la mise en évidence de l’implication de réseaux différents en fonction de stimulations différentes ou d’un état pathologique. / The comprehension of cerebral operations is in constant evolution since the rise of the neurosciences.New methods of imagery made it possible to highlight an architecture of our brain in complex networks.The purpose of my work is to develop a method to find the most representative networks of a group of subjects in Functional MRI.In the first step, I developed a method to reduce the fMRI data size based on clustering. I introduced a new characterization of functional information by the profile of connectivity. This one makes it possible to reduce the variance induced by the noise present within the data of Functional MRI.Moreover this profile does not require a priori information on the data contrary to the traditional inferential methods.In the second step, I developed a method to identify common networks on a group of subjects while taking into account of spatial and functional inter-subjects variability. The networks obtained can then be characterized by their spatial organization but also by their inner connectivity links.This method also allows the comparison of the networks of various groups of subjects, making it possible to highlight the implications of different networks according to different stimulations or pathological states.

Thesis advisor: Alexa H. Veenema / The poorly understood, but robust sex differences in prevalence, symptom severity, and treatment responses of many psychiatric disorders characterized by social dysfunction signifies the importance of understanding the neurobiological mechanisms underlying sex differences in the regulation of social behaviors. One potential system involved is the oxytocin (OT) system. OT is an evolutionarily conserved neuropeptide that has been implicated in the regulation of a variety of social behaviors in rodents and humans. This thesis aims to clarify the role of OT in sex-specific regulation of social behavior and brain function in rats. Study 1 characterized sex differences in the OT system in the brain, and found that males show higher OT receptor (OTR) binding densities in several forebrain regions compared to females. Studies 2 and 3 then determined the relevance of these sex differences in OTR binding densities for the sex-specific regulation of social behavior using pharmacological manipulations of the OTR and in vivo measurement of OT release. Study 2 focused on the function of the OT system in the posterior bed nucleus of the stria terminalis (BNSTp), because this region showed the largest sex difference in OTR binding density, and is part of the core social behavior network. Results show that endogenous OT in the BNSTp is important for social recognition in both sexes, but that exogenous OT facilitated social recognition in males only. Furthermore, social recognition in males, but not in females, was associated with higher endogenous OT release in BNSTp. This study is the first to provide a link between sex differences in OTR binding density and OT release with sex-specific regulation of social recognition by OT. Study 3 focused on amygdala subregions because these regions were found to show sex-specific correlations of OTR binding density with social interest. Results show that the OT system modulates social interest in the central amygdala (CeA), but not the medial amygdala, in sex-specific ways, with activation of the OTR in the CeA facilitating social interest in males, but not in females. These results provide evidence that the CeA is a brain region involved in the sex-specific processing of social stimuli by the OT system. Finally, Study 4 examined whether sex differences in OTR binding densities in forebrain regions lead to sex-specific brain activation in response to OT. Functional magnetic resonance imaging was used to examine blood oxygen level-dependent (BOLD) activation in awake male and female rats following central or peripheral administration of OT. Central OT administration induced sex differences in BOLD activation in numerous brain regions (including several regions with denser OTR binding in males), in which males showed predominantly higher activation compared to females. Peripheral OT administration also induced sex differences in BOLD activation, but in fewer brain regions and in different brain regions compared to central OT, indicating that the pattern and the magnitude of sex differences in neural activation induced by OT strongly depend on the route of administration. Together, outcomes of this thesis provide novel insight into the sexual dimorphic structure and function of the OT system in rats, and highlights the fact that research seeking a full understanding of the role of the OT system in behavioral and brain responses is incomplete without the inclusion of both sexes. These results may be informative given the increasing popularity of the use of OT as a potential therapeutic agent in the treatment of social dysfunction in sex-biased psychiatric disorders. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Thesis advisor: Lisa Barrett / Researchers have wondered how the brain creates emotions since the early days of psychological science. With the advent of neuroimaging techniques in the early 1990's and a surge of studies in affective neuroscience in recent years, scientists are now poised to answer this question. In this paper, I present the most up-to-date and statistically advanced meta-analytic summary of the human neuroimaging literature on emotion. I compare the locationist approach (i.e., that emotion categories consistently and specifically correspond to distinct brain regions) with the psychological construction approach (i.e., that emotions are constructed of more general brain networks not specific to emotions) to better understand the brain basis of emotion. I begin by outlining the set of brain regions consistently activated across all studies of emotion experience and perception. I next report findings from two sets of analyses probing the brain basis of discrete emotion categories. The first types of analysis demonstrates the brain regions that are consistently associated with the experience and perception of anger, disgust, fear, happiness and sadness across studies. The second type of analysis demonstrates the mental states (e.g., emotion experience or perception, cognitive load, locus of attention, mental response to methods, etc.) that are consistently associated with activity in given brain locations across studies. Overall, there was little evidence that discrete emotion categories can be localized consistently and specifically to individual brain regions. Instead, I found evidence that is consistent with a psychological construction approach to the mind: a set of common processes corresponding to interacting brain networks constitute emotion experience and perception across a range of emotion categories. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.