In cases of temporal lobe epilepsy, seizures are often controlled by anterior temporal lobe resection. However, an assessment of the impact of surgery on language is required. Currently-used assessments are either non-specific within regions or use functional magnetic resonance imaging (fMRI), which can suffer signal distortion in the temporal lobes due to the presence of airways. Magnetoencephalography (MEG) shows a complimentary sensitivity, but has not been used for laterality assessment. We present a method that combines fMRI with MEG for optimized sensitivity. MEG activation maps were generated using a beamformer, showing activity in the anterior temporal lobes and lateral occipital cortex. fMRI showed activation in medial temporal lobe regions, the frontal poles and the hippocampus, an area of clinical concern during surgical planning. The present study introduces a method for integrating MEG and fMRI activation to create high-resolution laterality maps in regions of concern for epilepsy.

Genome wide association studies have provided evidence for a significant association between ZNF804A (zinc finger protein 804A) - specifically the intronic single nucleotide polymorphism (SNP) rs1344706 - and schizophrenia, but little is known about the function of the gene or the effects of the SNP. By studying post-mortem human brain tissue, I characterised ZNF804A immunoreactivity in adult and foetal human brain and investigated effects of diagnosis and rs1344706 genotype on ZNF804A mRNA and protein expression. Secondly, I looked in a large sample of healthy volunteers (n=922) at the effects of rs1344706 on brain structure using volumetry and voxel based morphometry (VBM). Furthermore, I recruited healthy volunteers who were either homozygous for the risk allele or homozygous for the non-risk allele (n=50). They participated in magnetoencephalography (MEG) and magnetic resonance (MR) sessions in which brain activity was measured during a working memory task, a visual processing task, and rest. Using magnetic resonance spectroscopy, also neurotransmitter levels were assessed. The experiments conducted for this thesis showed for the first time that ZNF804A immunoreactivity can be detected in both foetal and adult human brain and that it is mainly localised to layer III pyramidal cells, with a granular subcellular distribution throughout the cytoplasm. No effect of rs1344706 on mRNA and protein expression was found. In our structural MRI study, rs1344706 did not affect macroscopic brain structure as measured by volumetry and VBM, and given the large sample size, this seems a convincing negative. However, we did find that rs1344706 alters prefrontal-hippocampal connectivity, with increased connectivity being observed in risk homozygotes. Additionally, using MEG, we found an effect of ZNF804A genotype on hippocampal connectivity in the theta band (4-8Hz), with non-risk homozygotes displaying more connectivity. This finding provides a first clue as to the mechanisms that might underlie the previously observed effects of rs1344706 on prefrontal-hippocampal connectivity. Future studies will need to elucidate the actual function of the ZNF804A protein, in order to bridge the gap between the molecular and neuroimaging findings described in this thesis.

The human brain is composed of distributed networks that connect a disproportionately large neocortex to the brainstem, cerebellum and other subcortical structures. New methods for analyzing non-invasive imaging data have begun to reveal new insights into human brain organization. These methods permit characterization of functional interactions within and across brain networks, and allow us to appreciate points of departure between the human brain and non-human primates. / Psychology

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.

Predicting teenage drug use is key to understanding the etiology of substance abuse. However, classic predictive modeling procedures are prone to overfitting and fail to generalize to independent observations. To mitigate these concerns, cross-validated logistic regression with elastic-net regularization was used to predict cannabis use by age 16 from a large sample of fourteen year olds (N=1,319). High-dimensional data (p = 2,413) including parent and child psychometric data, child structural and functional MRI data, and genetic data (candidate single-nucleotide polymorphisms, "SNPs") collected at age 14 were used to predict the initiation of cannabis use (minimum six occasions) by age 16. Analyses were conducted separately for males and females to uncover sex-specific predictive profiles. The performance of the predictive models were assessed using the area under the receiver-operating characteristic curve ("ROC AUC"). Final models returned high predictive performance (generalization mean ROC AUCmales=.71, mean ROC AUCfemales=.81) and contained psychometric features common to both sexes. These common psychometric predictors included greater stressful life events, novelty-seeking personality traits of both the parent and child, and parental cannabis use. In contrast, males exhibited distinct functional neurobiological predictors related to a response- inhibition fMRI task, whereas females exhibited distinct neurobiological predictors related to a social processing fMRI task. Furthermore, the brain predictors exhibited sex- specific effects as the brain predictors of cannabis use for one sex failed to predict cannabis use for the opposite sex. These sex-specific brain predictors also exhibited drug- specific effects as they failed to predict binge-drinking by age 16 in an independent sample of youths. When collapsed across sex, a gene-specific analysis suggested that opioid receptor genetic variation also predicted cannabis use by age 16. Two SNPs on the gene coding for the primary mu-opioid receptor exhibited genetic risk effects, while one SNP on the gene coding for the primary delta-opioid receptor exhibited genetic protective effects. Taken together, these results demonstrate that adolescent cannabis use is reliably predicted in males and females from shared and unique biobehavioral features. These analyses also underscore the need for refined predictive modeling procedures as well as sex-specific inquiries into the etiology of substance abuse. The sex-specific risk-profiles uncovered from these analyses might inform potential etiological mechanisms contributing to substance abuse in adolescence as all predictors were measured prior to the onset of cannabis use.

Decision-making is a fundamental process of human thinking and behavior. In engineering design, decision-making is studied from two different points of view: users and designers. User focused design studies tend to investigate ways to better inform the design process through the elicitation of preferences or information. Designer studies are broad in nature, but usually attempt to illustrate and understand some aspect of designer behavior, such as ideation, fixation, or collaboration. Despite their power, both qualitative and quantitative research methods are ultimately limited by the fact that they rely on direct input from the research participants themselves. This can be problematic, as individuals may not be able to accurately represent what they are truly thinking, feeling, or desiring at the time of the decision. A fundamental goal in both user- and designer-focused studies is to understand how the mind works while individuals are making decisions. This dissertation addresses these issues through the use of complementary behavioral and neuroimaging experiments, uncovering insights into how the mind processes design-related decision-making and the implications of those processes. To examine user decision-making, a visual conjoint analysis (preference modeling approach) was utilized for sustainable preference judgments. Here, a novel preference-modeling framework was employed, allowing for the real time calculation of dependent environmental impact metrics during individual choice decisions. However, in difficult moral and emotional decision-making scenarios, such as those involving sustainability, traditional methods of uncovering user preferences have proven to be inconclusive. To overcome these shortcomings, a neuroimaging approach was used. Specifically, study participants completed preference judgments for sustainable products inside of a functional magnetic resonance imaging (fMRI) scanner. Results indicated that theory of mind and moral reasoning processes occur during product evaluations involving sustainability. Designer decision-making was explored using an analogical reasoning and concept development experiment. First, a crowdsourcing method was used to obtain meaningful analogical stimuli, which were validated using a behavioral experiment. Following this, fMRI was used to uncover the neural mechanisms associated with analogical reasoning in design. Results demonstrated that analogies generally benefit designers; particularly after significant time on idea generation has taken place. Neuroimaging data helped to show two distinct brain activation networks based upon reasoning with and without analogies. We term these fixation driven external search and analogically driven internal search.. Fixation driven external search shows designers during impasse, as increased activation in brain regions associated with visual processing causes them to direct attention outward in search of inspiration. Conversely, during analogically driven internal search, significant areas of activation are observed in bilateral temporal and left parietal regions of the brain. These brain regions are significant, as prior research has linked them to semantic word-processing, directing attention to memory retrieval, and insight during problem solving. It is during analogically driven internal search that brain activity shows the most effective periods of ideation by participants.

In everyday life, people are interacting with the Internet. The emergence of this phenomenon has been positively contributing to the rapid development of our society in the last decades. However, negative reports about excessive usage are coming to the surface and questions about potential negative consequences are being raised. Internet addiction (IA) has been suggestedas a new type of disorder. There is a new field of research emerging with the aim to investigate its nature. This review compiles the most relevant literature on neuroimaging techniques used to identify the underlying neurobiological mechanisms of IA. Based on identified comorbidity between IA and attention-deficit hyperactivity disorder (ADHD), a comparison between the neural correlates of IA and ADHD is attempted, in order to illustrate the importance of bringing more attention to IA. The findings present structural, functional and neurochemical alterations in brain regions associated with emotional processing, cognitive control and reward processing. Similarities between the two disorders interms of structural and functional alterations in regions associated with emotional processing and cognitive control are highlighted.Limitations regarding lack of consensus of the operational definition, narrow selection criteria of participants and a need for subcategories inside the term IA are pointed out. The thesis concludes that as of now the discovered alterations may be considered as biological markers underlying the disorder and IA is a field of research worthy of more attention.

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.

Thesis advisor: Elizabeth A. Kensinger / Individuals' short- and long-term goals can influence the constructive nature of autobiographical memory recall. The overarching aim of this dissertation was to examine how emotion regulation goals in particular might modulate autobiographical recall at both a behavioral and neural level. In Chapter 1, a new behavioral task instructed individuals to cognitively reappraise the emotions associated with negative and positive events. Results revealed that such emotion regulation goals influence the emotional and other subjective experiences associated with recall, such that up-regulation instructions were linked to greater reported levels of emotional intensity, sensory detail, and recollection (e.g., reliving), and vice-versa for down-regulation instructions. In Chapter 2, functional magnetic resonance imaging (fMRI) was used as participants were instructed to decrease, increase, or maintain the emotions associated with negative autobiographical events. Decreasing emotional intensity primarily engaged neural activity in regions previously implicated in cognitive control (e.g., dorsal and ventral lateral prefrontal cortex), emotion generation and processing (e.g., amygdala, insula), and visual imagery (e.g., precuneus) during an early phase of recall as participants searched for and retrieved events. In contrast, increasing emotional intensity engaged similar regions as individuals prepared to recall negative events (i.e., before a memory cue was presented) and again as they later elaborated upon the details of the events they had recalled. In Chapter 3, individual differences in habitual use of cognitive reappraisal were measured and their relation to neural activity during autobiographical recall was examined. Results revealed that, even when not explicitly instructed to reappraise, habitual use of reappraisal was broadly associated with neural activity in cognitive control regions (e.g., dorsal and ventral lateral prefrontal cortex, dorsal anterior cingulate cortex) as well as emotion processing regions (e.g., amygdala, insula) across memories that varied in their emotionality and specificity. Taken together, these results suggest that short- and long-term emotion regulation goals can influence the construction of autobiographical memories on both behavioral and neural levels. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

RACIONAL: A obesidade caracteriza-se por um excesso de tecido adiposo branco que causa morbidades metabólicas, mecânicas e a morte de aproximadamente 2,8 milhões de pessoas anualmente. Sua fisiopatologia envolve alterações em mecanismos que interagem no cérebro, sejam humorais, neurais e comportamentais, os quais podem ser eliciados por alimentos. Por sua vez, técnicas de neuroimagem funcional, como o Single-photon Emission Tomography (SPECT), surgiram como ferramentas para avaliar alterações funcionais in vivo. Por isso, questionamos se imagens de SPECT cerebral, alteradas após a ingestão de glicose em comparação a um teste controle com água, explicariam, pelo menos em parte, o comportamento alimentar da obesidade. OBJETIVOS: Comparar a perfusão (ativação) cerebral de imagens de SPECT, após ingestão de água vs. glicose, em mulheres obesas e com peso normal. Correlacionar a intensidade da perfusão encontrada com níveis sanguíneos de leptina, insulina e glicemia, bem como com a quantidade de gordura corporal. MATERIAIS E MÉTODOS: 10 mulheres com e 10 sem obesidade (n = 20) foram submetidas à SPECT cerebral duas vezes, após marcação pelo [99mTc]-ECD 30 minutos após ingestão de 300 mL de água e de uma solução com 75 gramas de glicose, em dias separados (40 SPECTs), tendo sido cada sujeito controle de si mesmo. As imagens foram comparadas intragrupo e entre grupos por meio do software Statistical Parametric Mapping. Modelos de efeitos mistos foram usados para avaliar correlações entre as variáveis. RESULTADOS E DISCUSSÃO: Mulheres obesas apresentam maior ativação em regiões da Default Mode Network e da Salience Network após o teste com água. Enquanto as obesas apresentam-se mais engajadas na percepção dos processos fisiológicos (como fome e sede) na situação basal, com água, apenas aquelas com peso normal parecem responder às alterações desses processos eliciadas pelo alimento oferecido. Após estímulo com glicose, apenas o grupo sem obesidade aumentou a perfusão em regiões relacionadas à recompensa e ao controle do comportamento, como corpo estriado e córtices orbitofrontal e pré-frontal. A perfusão nestas áreas apresentou correlação negativa com a interação entre leptina e insulina (Coef. = - 0,001, p = 0,003). Além disso, tais regiões recebem aferências dopaminérgicas e, por isso, temos como hipótese que déficits na sinalização da dopamina explicariam os achados encontrados. CONCLUSÃO: A ingestão de glicose eliciou respostas relacionadas à recompensa alimentar normal e a um controle apropriado sobre o apetite nas mulheres sem obesidade, não sendo observado o mesmo nas obesas, processo do qual parece participar a interação entre insulina e leptina e déficits na sinalização dopaminérgica. / RATIONALE: Obesity is an excess of white adipose tissue that causes mechanical, metabolic injuries and mortality of approximately 2.8 million people annually. Its physiology involves alterations in humoral, neural and behavioral mechanisms that interact in brain, which can be elicited by nutrients. Functional neuroimaging techniques, such as Single-photon Emission Tomography (SPECT), arise as tools to evaluate abnormalities in vivo. Therefore, we argue if changes in brain images, after intake of glucose, compared to a test with water, would explain, at least in part, the altered feeding behavior of obesity. OBJECTIVES: Compare perfusion (activation) of brain SPECT images after water vs. glucose intake in obese and normal weight volunteers. Correlate the intensity of perfusion found with blood levels of leptin, insulin and glucose, as well as with the amount of body fat. MATERIALS AND METHODS: 10 women with and 10 women without obesity (n = 20) underwent SPECT twice, after labeling by the [99mTc]-ECD 30 minutes after ingesting 300 ml of water and a solution of 75 grams glucose, on separate days (40 SPECTs) being each subject control of yourself. The images were compared between groups and intragroup using Statistical Parametric Mapping. Mixed effects models were used to assess correlations between variables. RESULTS AND DISCUSSION: Obese women have higher activation in regions of the Default Mode Network and Salience Network after test with water. While obese have become more engaged in the perception of physiological processes (such as hunger and thirst) at baseline, with water, this group do not seem to respond to changes of these processes elicited by the food offered. After glucose intake, only those with normal weight increased perfusion in regions related to food reward and behavioral control, such as striatum and orbitofrontal and prefrontal cortices. The perfusion in these areas was negatively correlated with the interaction between leptin and insulin (Coef = -. 0.001, p = 0.003). In addition, these regions receive dopaminergic afferents and therefore we hypothesized that deficits in dopamine signaling could explain the results observed. CONCLUSION: Glucose intake elicited responses related to normal food reward and the appropriate control over appetite in women without obesity, not being observed the same in obese volunteers, a process in which the interaction between insulin and leptin, as well as dopamine signaling seems to participate.