The study of brain nuclei in neuroimaging poses challenges owing to its small size. Many neuroimaging studies have been reported for effectively locating these nuclei and characterizing their functional connectivity with other regions of the brain. Hypothalamus, Locus Coeruleus, and Ventral Tegmental area are such nuclei found in the human brain, which are challenging to visualize owing to their size and lack of tissue contrast with surrounding regions. Resting-state functional magnetic resonance imaging (rsfMRI) analysis on these nuclei enabled researchers to characterize their connectivity with other regions of the brain. An automated method to successfully isolate voxels belonging to these nuclei is still a great challenge in the field of neuroimaging. Atlas-based segmentation is the most common method used to study the anatomy and the functional connectivity of these brain nuclei. However, atlas-based segmentation has shown inconsistency due to variation in brain atlases owing to different population studies. Therefore, in this study, we try to address the research problem of brain nuclei imaging using a clustering-based approach. Clustering-based methods separate of voxels utilizing their structural and functional homogeneity to each other. This type of method can help locate and cluster the voxels belonging to the nuclei. Elimination of erroneous voxels by the use of clustering methods would significantly improve the structural and functional analysis of the nuclei in the human brain. Since several clustering methods are available in neuroimaging studies, the goal of this study is to find a robust model that has less variability across different subjects. Non-parametrical statistical analysis was performed as functional magnetic resonance imaging (fMRI) based studies are corrupted with noise and artefact. Statistical investigation on the fMRI data helps to assess the significant experimental effects.

<p>The aim of this research study was to examine the clinical, behavioural and neurobiological characteristics of children who are considered to be at increased risk for developing anxiety disorders. The study population included high-risk children who have at least one parent with social phobia and normal-risk control subjects. The first objective of the study was to examine the prevalence of anxiety disorders in high-risk children. We determined the proportion of high-risk children who met criteria for a psychiatric disorder using structured clinical interviews and assessed symptom severity using measures of anxiety and depression. We found the prevalence of anxiety disorders to be elevated in high-risk children with 77% meeting criteria for a lifetime psychiatric disorder. High-risk subjects also had significantly higher levels of anxiety symptoms relative to normal-risk subjects. The second objective of the study was to examine threat-related attention processing in high-risk and normal-risk children using the dot-probe attention orienting task. We compared probe detection reaction times of high-risk children and normal-risk control children when they were exposed to emotional facial stimuli. We did not find any significant within-group or between-group differences in reaction times in our high-risk and normal-risk subjects. However, we did observe a trend towards longer reaction times in high-risk subjects for all trial types relative to normal-risk subjects, which could indicate general processing deficits in the high-risk group. The third objective of this study was to examine the activity of emotion processing brain regions using functional magnetic resonance imaging (<em>f</em>MRI) in children who are at increased risk for developing anxiety disorders. We compared the blood oxygenation level dependant (BOLD) response while high-risk and normal-risk subjects were engaged in the dot probe attention orienting task. Using <em>f</em>MRI, the BOLD response was measured while subjects were exposed to masked emotional (angry, happy or neutral) facial stimuli. We found increased activation of several frontal, temporal and limbic regions in high-risk subjects relative to normal-risk subjects during the presentation of emotional facial stimuli. These regions included the prefrontal cortex, anterior cingulate, hippocampus, insula, basal ganglia and temporal regions. To our knowledge this is the first study to characterize a sample of children at-risk for anxiety disorders using clinical, behavioural and neuroimaging data. The findings from this study demonstrate that high-risk children experience heightened anxiety symptoms and that they also present with functional abnormalities of brain regions involved in emotion processing. These results highlight the need for early identification and intervention for children at-risk for anxiety disorders. Future studies should aim for longitudinal study designs combined with neuroimaging techniques to examine changes in anxiety symptoms over time and to study the effects of treatment on the function of limbic and prefrontal structures in children at-risk for anxiety disorders.</p> / Doctor of Philosophy (PhD)

Life satisfaction is a key aspect of subjective well-being (SWB) and is often referred to as an individual’s cognitive assessment of their overall life. Measured by tools such as the Satisfaction with Life Scale (SWLS), life satisfaction is crucial for reliably assessing SWB. It serves as a stable measure, reflecting long-term judgements of SWB - unlike affect measures that capture more short-term judgements influenced by situational variability. While the SWLS demonstrates internal consistency, the neural correlates of life satisfaction remain largely unknown, limiting our comprehension of SWB’s cognitive dimension. This systematic review aims to bridge the gap by comprehensively examining relevant literature, emphasizing resting-state neuroimaging studies. Despite methodological differences, the authors discovered relationships between brain structures and life satisfaction, revealing a spectrum of associations ranging from positive to negative, alongside correlations with varying strengths. These structures include the left SFG, bilateral MFG, frontoinsular cortex, and other areas correlated with microstructural connections, including the SPL, IPL and TPJ. Considering the novelty and limited establishment of this subject, ongoing research is crucial for uncovering the precise neural correlates of life satisfaction.

Major depressive disorder (MDD) is considered the current leading cause of disability worldwide (Friedrich, 2017), yet the recovery process in MDD, including neurobiological underpinnings, clinical features and optimal approaches to treatment remains ambiguous. Current definitions of recovery are disputed and involve measures considered subjective in nature, such as thresholds for questionnaires and clinical interviews of symptoms and their duration (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). Symptom-based measures, although informative of clinical presentation, are not informative of neurobiological underpinnings that may persist even when symptoms are reduced. Indeed, even after treatment, persistent residual symptoms, impairments in quality of life, and vulnerabilities for future return to more severe psychopathology persist (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessment of neural mechanisms of recovery in MDD, efforts toward developing novel treatment approaches that are able to address neural processes of illness and to provide sustained remission are slowed. The following collection of studies provide neural and clinical insights into MDD recovery and relate findings to potential treatment approaches that are optimized to individual differences in symptoms and neural functioning and able to address neural vulnerabilities to provide sustained remission. In pursuit of individualized treatment selection in MDD, study one involved a meta-analysis of prior prognostic fMRI studies of response to cognitive behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI) in MDD. Study one also reported on the application of resulting meta-analytic regions (subgenual and perigenual anterior cingulate cortex) in a confirmatory MDD sample. Although regions showed some predictive potential in the confirmatory sample, when predicting SSRI response, effects were inconsistent with prior studies, suggesting methodological confounds may hinder ready translation. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after acute treatment (CBT or SSRI) and found that persistent residual depression symptoms and quality of life deficits were common. In light of the normality of chronic symptoms and impairment, the third study evaluated neural features of treatment (CBT) resistance in MDD within the context of neural mechanisms of change. The third study found a vermis-centered cerebellar cluster that was unresponsive to CBT, whereas prefrontal and parietal cortical regions were responsive, providing support of prior theories that CBT directly affects cognitive control and cortical regulatory processes in contrast to salience-driven subcortical functioning (Clark and Beck, 2010; DeRubeis et al., 2008; Frewen et al., 2008; Mayberg, 2003). In consideration of findings, clinical recommendations that pertain to treating residual symptoms and associated neural features toward asymptomatic remission are provided. Future research directions are also provided regarding neuroscience informed precision medicine, current therapy and medication practices, and the larger picture of MDD chronicity broadly. / Doctor of Philosophy / Major depressive disorder (MDD) is considered the leading cause of disability worldwide (Friedrich, 2017), yet there are many aspects of MDD recovery that are unclear such as neural and clinical features and optimal treatment approaches. Current definitions of recovery involve questionnaires and interviews, which may not accurately represent all aspects of recovery (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). For example, they do not assess neural or biological features of recovery that may continue even if symptoms improve. Indeed, even after treatment, often some minimal depression symptoms, impairments in quality of life, and risks for future more severe symptoms continue (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessing neural features of MDD and recovery, developing treatments that can address illness- related neural features and provide sustained recovery are slowed. The following studies report on neural and clinical features of MDD recovery to approach treatment and sustained recovery with consideration of individual differences in symptoms and neural functioning. Pursuing neuroimaging measures of individual differences to inform treatment selection, study one involved a statistical review of prior neuroimaging prediction studies of MDD treatment. Study one also reported on whether the regions suggested by the statistical review to inform treatment selection would be useful when applied to a prior MDD treatment study. Findings suggested functioning of the identified brain regions can help inform treatment selection, but method differences among studies included in the review hinder application of resulting regions. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after treatment and found at least minimal depression symptoms as well as impairments in quality life commonly continued after treatment. In light of persistent symptoms and impairment, the third study aimed to identify neural features of MDD that did not respond to treatment, as well as neural features that were responsive to treatment. The third study found that therapy directly affects cognitive control processes, but may not affect brain regions associated more with emotion-driven processes. Clinical recommendations pertain to treating depression symptoms that continue after treatment toward asymptomatic recovery. Future research directions pertain to neuroscience informed treatment selection, current therapy and medication practices, and the larger picture of persistent depression symptoms broadly.

The Blood Oxygen Level Dependent (BOLD) signal provides indirect estimates of neural activity. The parameters of this BOLD signal can give information about the pathophysiological state of the brain. Most of the models for the BOLD signal are overparameterized which makes the unique identification of these parameters difficult. In this work, we use information from multiple neu- roimaging sources to get better estimates of these parameters instead of relying on the information from the BOLD signal only. The mulitmodal neuroimaging setup consisted of the information from Cerebral Blood Volume (CBV) ( VASO-Fluid-Attenuation-Inversion-Recovery (VASO-FLAIR)), and Cerebral Blood Flow (CBF) (from Arterial Spin Labelling (ASL)) in addition to the BOLD signal and the fusion of this information is achieved in a Particle Filter (PF) framework. The trace plots and the correlation coefficients of the parameter estimates from the PF reflect ill-posedness of the BOLD model. The means of the parameter estimates are much closer to the ground truth compared to the estimates obtained using only the BOLD information. These parameter estimates were also found to be more robust to noise and influence of the prior. / Master of Science

Sustainability is inherently a complex problem that requires new ways of thinking. To solve grand challenges such as climate change, environmental degradation, and poverty, engineers cannot rely on the same models of thinking that were used to create these problems. Engineering education is therefore critical to advance sustainable engineering solutions. Improving education relies on understanding of cognition of thinking and designing for sustainability. In this thesis, a nascent neuroimaging technology called functional near-infrared spectroscopy (fNIRS) was used to measure cognition among engineering students thinking about sustainability. fNIRS provides an opportunity to investigate how sustainability in design influences cognition, and how different concept generation techniques help students consider many aspects related to sustainability. The first manuscript provides evidence that engineering students perceive sustainability in design as a constraint, limiting the number of solutions for design and decreasing the cognitive efficiency to generate solutions. Senior engineering students generated fewer solutions than freshmen, however, seniors were better able to cognitively manage the sustainability parameter with higher cognitive efficiency. The second manuscript investigates the cognitive difference when generating concepts using concept listing or concept mapping. The results indicate that concept mapping (i.e. intentionally drawing relationships between concepts) leads to more concepts generated. An increase in concepts during concept mapping was also observed to shift cognitive load in the brain from regions associated with process sequencing to regions associated with cognitive flexibility. This research demonstrates the feasibility of fNIRS applied in engineering research and provides more understanding of the cognitive requirements for sustainability thinking. / M. S. / Sustainability brings new challenges to engineering design. To advance the practice of sustainable engineering, engineers are expected to be able to efficiently tackle socio-technical problems using a systems perspective. Engineering education is expected to help engineering students to achieve this goal. Improving education relies on understanding of mental process of thinking and designing for sustainability. In this research, a nascent neuroimaging technology-functional near-infrared spectroscopy (fNIRS) has been used to measure the cognition of engineering students thinking for sustainability. fNIRS enables us to investigate how sustainability requirements in design influence the cognition of design process, and how different concept generation ways help students understand sustainability. The first manuscript provides evidence that sustainability in design constraint, limiting the number of solutions for design and decreasing the cognitive efficiency to generate solutions. Senior engineering students generated fewer solutions than freshmen, however, seniors showed advantage to handle sustainability requirements with higher cognitive efficiency. The second manuscript investigates the cognitive difference of two concept generation ways using concept listing or mapping. The results indicate that concept mapping leads to more concepts related to sustainability and enables the cognitive load shift from regions associated with sequencing processing to regions associated with cognitive flexibility. This research demonstrates the feasibility of fNIRS applied in engineering research for sustainability and provides more understanding of the cognitive requirements for sustainability thinking.

This dissertation investigates the effects of multisensory biophilic restorative experiences on how engineers feel, think, and design. While previous research on the restorative effects of biophilic experiences have mostly focused on the benefits of visual exposure, less is known about the potential of exposure to auditory and multisensory stimuli. Moreover, a knowledge gap exists in regards to how the cognitive benefits of biophilic restorative experiences influence performance in real-world cognitive tasks, like design. To address the identified knowledge gaps, a randomized controlled trial with 154 participants was conducted, exploring the restorative effects of biophilic auditory, visual, and multisensory (auditory + visual) experiences after induced psychosocial stress. To assess the potential influence on the performance of a real-world cognitive tasks, an open-ended design task was given to participants following the exposure period. Dependent variables tracked covered three key domains of the research question: (1) psychological and physiological responses (feel), (2) neurocognitive responses (think), and (3) design originality and incorporation of biophilia (design). Results showed that the biophilic auditory experience induced higher physiological arousal during and after exposure, while the visual and multisensory conditions presented evidence of increased neural efficiency. The biophilic conditions assisted in restoring cognitive resources and improved prefrontal cortical functional connectivity, specifically within main hubs of the Default Mode Network (DMN). However, better engagement of the DMN did not result in more original design products. No significant differences were found for exploration of the design space across conditions. Interestingly, the visual group incorporated significantly more biophilic design patterns, such as "Visual Connection with Nature" and "Presence of Water", in their design concepts. This finding suggests a potential priming effect, where exposure to biophilic stimuli influenced designers' choices towards more nature-connected ideas. The study here presented contributes to the understanding of biophilic restorative experiences' nuanced effects on physiology, neurocognition, and design cognition. Accessibility and availability of the interventions tested affords readily replication of the experiment design and application of findings to the general public. / Doctor of Philosophy / This dissertation explores how exposure to simulated nature experiences through different senses affects how engineers feel, think, and design. Two main environmental psychology theories propose that nature experiences can aid in the recovery from stressful states and mental fatigue. The Kaplans' Attention Restoration Theory suggests that looking at nature can help the brain recover from overuse by allowing it to restore attentional resources. Roger Ulrich's Stress Reduction Theory proposes that nature experiences can reduce stress by calming the body and the mind. While previous studies have mainly explored the effects of exposure to nature through visual experiences, the study presented here examines the effects of exposure to nature-based sounds (birdsong and water sounds), as well as exposure to the combination of sounds and visuals (indoor plants, nature-inspired art, and daylight). Additionally, it investigates how the potential benefits to the brain and mind influence performance in real-world tasks like designing. To explore these effects, 154 engineering students were randomly assigned to different groups and exposed to nature sounds, nature visuals, or a combination of both, after being induced to a stressful state. After the exposure period, participants were given an open-ended design task. Throughout the experiment, participants' bodily responses were tracked by a wrist-worn device and participants' brain activity was tracked by a brain-imaging headset. Design concepts produced in the design task were assessed for originality and for the incorporation of nature-inspired ideas. Results showed that listening to nature sounds increased arousal of the body both during and after the exposure period. Visual, as well as combined auditory and visual exposure improved brain efficiency. All nature experiences helped restore mental resources and improved brain connectivity, particularly in areas associated with mind wandering. Although better brain connectivity did not result in more original design concepts, interestingly, participants in the visual exposure group incorporated more nature-related features, like bodies of water and natural views, into their designs. This finding suggests that seeing nature might inspire more nature-connected design ideas. This study enhances our understanding of how nature experiences affect the body, brain, and mind. The interventions tested can be easily replicated and applied in everyday settings so that anyone can benefit off of their outcomes.

Many psychiatric disorders are characterized by difficulties in working towards long-term goals. Effort-based decision-making (EBDM) provides a useful framework for understanding this phenomenon, particularly for parsing motivation into various components, and exploring the underpinnings of cost-benefit computations. Importantly, large changes in arousal, like those introduced by strong emotions and stress, can significantly influence high-order cognitive processes. However, the mechanistic properties underlying associations between emotions and various components of EBDM remain unclear, particularly at psychological, neurological and endocrinological levels. The following experiments were designed to examine the effect of positive and negative emotions on various components of EBDM across psychiatric conditions characterized by motivational and impulse-related deficits. In the first experiment, comparing emotional versus behavioural inhibitory systems in binge eating disorder, inverse relationships between disgust sensitivity, inhibitory control and binge-eating behaviours were found, suggesting unique maintenance functions of cognitive-affective links with emotion regulation on eating attitudes. In the second experiment examining neural correlates of effort- and reward-processing in a cannabis using population, findings indicate fronto-striatal but also posterior cortical processing alterations during prospective signaling of effort and reward signals and during effort-reward information integration. In the final experiment assessing the effects of childhood trauma on acute stress responses and gambling urges in a population of problem gamblers, increased reports of childhood trauma were noted relative to a healthy control group. Childhood trauma subsequently predicted subjective and physiological stress responses, and emotional and physical neglect in childhood was further linked to increased gambling urges. Taken as a whole, these studies suggest that emotions plays a crucial role in moderating various components of EBDM, underscoring the significant impact of emotional states on higher-order cognitive functioning. / Dissertation / Doctor of Philosophy (PhD)

This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This paper presents the Social Phobia Psychotherapy Research Network. The research program encompasses a coordinated group of studies adopting a standard protocol and an agreed-on set of standardized measures for the assessment and treatment of social phobia (SP). In the central project (study A), a multicenter randomized controlled trial, refined models of manualized cognitive-behavioral therapy and manualized short-term psychodynamic psychotherapy are compared in the treatment of SP. A sample of 512 outpatients will be randomized to either cognitive-behavioral therapy, short-term psychodynamic psychotherapy or waiting list. Assessments will be made at baseline, at the end of treatment and 6 and 12 months after the end of treatment. For quality assurance and treatment integrity, a specific project using highly elaborated measures has been established (project Q). Study A is complemented by 4 interrelated add-on projects focusing on attachment style (study B1), on cost-effectiveness (study B2), on variation in the serotonin transporter gene in SP (study C1) and on structural and functional deviations of the hippocampus and amygdala (study C2). Thus, the Social Phobia Psychotherapy Research Network program enables a highly interdisciplinary research into SP. The unique sample size achieved by the multicenter approach allows for studies of subgroups (e.g. comorbid disorders, isolated vs. generalized SP), of responders and nonresponders of each treatment approach, for generalization of results and for a sufficient power to detect differences between treatments. Psychological and biological parameters will be related to treatment outcome, and variables for differential treatment indication will be gained. Thus, the results provided by the network may have an important impact on the treatment of SP and on the development of treatment guidelines for SP. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.