Exploring Functional Connectivity Across Borderline Personality Disorder, Post Traumatic Stress Disorder and Dissociative Disorder

The overall focus of this thesis relates to resting state functional connectivity (RSFC) of the default mode network (DMN) in borderline personality disorder (BPD), post traumatic stress disorder (PTSD) and dissociative disorders. Part one of the thesis systematically reviewed 19 studies investigating RSFC of the DMN in PTSD, BPD and dissociative disorders to establish the value of DMN in understanding the three psychopathology. Current research suggests that RSFC of the DMN is distinct when comparing participants with PTSD, participants with PTSD co-morbid with MDD, and healthy controls. In addition, studies also showed that RSFC of the DMN was associated with PTSD severity and trauma experiences. In terms of BPD, findings seem to indicate the presence of aberrant RSFC of the DMN when compared to healthy controls and bipolar disorder. However, in order to interpret these results, it is essential to consider the potential influence of co-morbid MDD. As there was only one research investigating dissociative disorder, it is premature to conclude if RSFC of the DMN is atypical in this disorder. Overall, the reviewed studies seems to indicate that the value of the DMN in understanding psychopathology is strongest in PTSD but lacking in BPD and dissociative disorder. Part one concludes by addressing current limitations and implications for future research. Part two presents an empirical study investigating RSFC of the DMN in participants with BPD and healthy controls. In order to further elucidate the associations with indices of core symptomatology, self-reports measures pertaining to dissociation, trauma, emotional dysregulation, general clinical symptomatology and personality psychopathology were also administered. The findings suggest that BPD participants display higher RSFC between core brain regions. However, as only one of the obtained finding remained significant after correcting for multiple comparisons, the results should be interpreted cautiously. Additionally, higher RSFC in BPD participants were also associated with higher self-reported trauma experiences, dissociation and general clinical symptomatology. Similarly, these results did not survive correction for multiple comparisons and hence should be further investigated in future studies. This section concluded by discussing implications of these findings and limitations of the current study. Part three provided a critical appraisal of the entire research process. Firstly, it considers the implications of the current study, namely the influence on therapeutic approaches, our understanding of BPD, PTSD and dissociation, reflections on the wider issues in neuroimaging studies and in BPD research. This is then followed by a discussion of the challenges and opportunities in research investigating multiple constructs. Lastly, whilst acknowledging the limitations of neuroimaging, the critical appraisal also put forth suggestions aimed at maximizing clinical utility of neuroimaging findings

Clinical correlates of emotional dysregulation in bipolar disorder spectrum: a case-control study

openL'attuale studio si propone di studiare e quantificare le differenze tra i pazienti con BD, quelli con BPD, e controlli sani in (a) disregolazione emotiva utilizzando Difficoltà nelle scale di disregolazione delle emozioni (DERS), (b) impulsività valutata da Barratt Inibiion Scale (BIS-11), (c) abusi della prima infanzia utilizzando il Child Trauma Questionnaire (CTQ) e (d) funzionamento quotidiano con il World Health Organization Disability Assessment Schedule (WHODAS.2). Questo studio si propone di aiutare i medici nel compito impegnativo di distinguere tra i pazienti con BD e BPD, contribuendo così al perfezionamento della diagnosi precoce di questi disturbi.The current study aims to investigate and quantify differences between patients with BD, those with BPD, and healthy controls in (a) emotional dysregulation using Difficulties in emotion dysregulation scales (DERS), (b) impulsivity assessed by Barratt Inhibition Scale (BIS-11), (c) early childhood abuses using the Child Trauma Questionnaire (CTQ) and (d) daily functioning with the World Health Organization Disability Assessment Schedule (WHODAS.2). This study aims to assist clinicians in the challenging task of distinguishing between patients with BD and BPD, thereby contributing to the refinement of the earlier diagnosis of these disorders

A Review of the Relation Between Dissociation, Memory, Executive Functioning and Social Cognition in Military Members and Civilians with Neuropsychiatric Conditions

Dissociative experiences, involving altered states of consciousness, have long been understood as a consequence or response to traumatic experiences, where a reduced level of consciousness may aid in survival during and after a traumatic event. Indeed, the dissociative subtype of post-traumatic stress disorder (PTSD-DS) was added recently to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Dissociative symptoms are present across a host of neuropsychiatric conditions, including PTSD, psychotic spectrum illnesses, anxiety and mood disorders. Transdiagnostically, the presence of dissociative symptoms is associated with a greater illness burden and reduced treatment outcomes. Critically, dissociative symptoms are related to impaired performance on measures of attention, executive functioning, memory, and social cognition and may contribute to the widespread cognitive dysfunction observed across psychiatric illnesses. Despite this knowledge, the relation between dissociative symptoms and reduced cognitive function remains poorly understood. Here, we review the evidence linking dissociative symptoms to cognitive dysfunction across neuropsychiatric disorders. In addition, we explore two potential neurobiological mechanisms that may underlie the relation between dissociative symptoms and cognitive dysfunction in trauma-related neuropsychiatric conditions. Specifically, we hypothesize that: 1) functional sensory deafferentation at the level of the thalamus, as observed in the defence cascade model of dissociation, may underlie reduced attention and arousal leading to progressive cognitive dysfunction and; 2) altered functional connectivity between key brain networks implicated in cognitive functioning may represent a critical neurobiological mechanism linking dissociative symptoms and cognitive dysfunction in patients with PTSD-DS and transdiagnostically

Emotional and behavioral symptoms in neurodegenerative disease: a model for studying the neural bases of psychopathology.

Disruptions in emotional, cognitive, and social behavior are common in neurodegenerative disease and in many forms of psychopathology. Because neurodegenerative diseases have patterns of brain atrophy that are much clearer than those of psychiatric disorders, they may provide a window into the neural bases of common emotional and behavioral symptoms. We discuss five common symptoms that occur in both neurodegenerative disease and psychopathology (i.e., anxiety, dysphoric mood, apathy, disinhibition, and euphoric mood) and their associated neural circuitry. We focus on two neurodegenerative diseases (i.e., Alzheimer's disease and frontotemporal dementia) that are common and well characterized in terms of emotion, cognition, and social behavior and in patterns of associated atrophy. Neurodegenerative diseases provide a powerful model system for studying the neural correlates of psychopathological symptoms; this is supported by evidence indicating convergence with psychiatric syndromes (e.g., symptoms of disinhibition associated with dysfunction in orbitofrontal cortex in both frontotemporal dementia and bipolar disorder). We conclude that neurodegenerative diseases can play an important role in future approaches to the assessment, prevention, and treatment of mental illness

Extended Functional Connectivity of Convergent Structural Alterations Among Anxiety Disorders: A Meta-Analysis and Functional Connectivity Analysis

Anxiety-related disorders are some of the most pervasive mental health disorders affecting adult and youth populations. Despite growing evidence of the neurobiology associated with anxiety-related disorders, a consensus on the neurobiological mechanisms of anxiety-related disorders remains to be elucidated. We first provide background literature on the reasoning behind this dissertation in Chapter 1. In Chapter 2, we conducted a neuroimaging meta-analysis on posttraumatic stress disorder to identify convergent structural and functional alterations associated with this anxiety-related disorder among adults. In Chapter 3, we conducted a neuroimaging meta-analysis to identify convergent structural alterations across diverse groupings of anxiety-related disorders among adults, adolescents, and youth. Chapter 3 included a contrast analysis to examine potential developmental effects of anxiety-related disorders associated with brain structure between adults, adolescents, and youth. In Chapter 4, we conduct an extended functional connectivity analysis to characterize functional profiles of the region of interests (ROIs) identified in Chapter 3. We provide concluding thoughts in Chapter 5. The present collection of studies provides implications for understanding the neurobiology of anxiety-related disorders and brain-based approaches to treatment

Neurobiological mechanisms of hallucinations in schizophrenia

All perception is a construct of the brain. Yet occasionally, sensory constructions emerge without origin in the physical world and are experienced as hallucinations. Hallucinations occur transdiagnostically, cross-culturally, and in all sensory modalities. They are common in people with schizophrenia, presenting in 60-80% of patients. Despite over 20 years of active neuroimaging research on hallucinations, the neural systems supporting these anomalous perceptual experiences remain disputed. This dissertation investigates the neurobiology of hallucinations, integrating research across structural and functional magnetic resonance imaging (MRI) to elucidate how hallucinations, chiefly in the context of schizophrenia, are supported by the brain, drawing on MRI indices of neurodevelopment. I introduce the phenomenon of hallucinations and motivate the utility of MRI for studying hallucinations. Considering their prevalence in other medical conditions, I conduct a meta-analysis and systematic review of the structural brain basis of hallucinations across diagnoses, primarily schizophrenia spectrum disorders and Parkinson’s disease. This illustrated distinct neuroanatomical organizations of grey matter associated with hallucinations that occur in neurodevelopmental compared to neurodegenerative disorders, which I hypothesise constitute at least two distinct mechanisms. Focussing on the neurodevelopmental mechanism characterized by fronto-temporal and insular grey matter reductions, I turn to the contribution of cortical sulcation, a product of second and third trimester neurodevelopmental processes, which has been robustly implicated in schizophrenia pathology, and, more recently, in hallucinations. Sulcal patterns derived from structural MRI provide a proxy in adulthood for early brain development. I studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MRI from the United Kingdom and Shanghai, China, stratified into those with and without hallucinations, and healthy controls from Shanghai. I first replicate the finding that left hemisphere paracingulate sulcus (PCS) length is reduced in patients who experience hallucinations, then demonstrate similar associations for superior temporal sulcus depth. Length and depth alterations occurred with focal deviations in sulcal geometry. The interindividual and interhemispheric variability of the PCS necessitated the development of semi-automated methods to characterize its morphology and validation to a manual protocol. I used structural covariance networks of the local gyrification index to investigate how specific sulcal deviations relate to global neurodevelopmental coordination, demonstrating that hallucinations correspond to increased covariance within and between salience and auditory networks. Hypothesizing structure-function relationships, I analyse resting-state functional MRI data from the same datasets described, finding significant interactions between PCS length and hallucinations status, but no main effects. There were no effects of hallucination status on salience and auditory network connectivity or in graph theoretical measures of connectivity, suggesting that resting-state connectivity is not a trait marker for hallucinations. Together, the discovery of neurodevelopmental alterations contributing to hallucinations provides mechanistic insight into the pathological consequences of prenatal origins. The interaction of sulcal alterations and hallucination status are associated with connectivity, which may have a role in the pathophysiology of hallucinations. I provide clear predictions and recommendations for future research.Gates Cambridge Scholarshi

The feeling of anger: From brain networks to linguistic expressions.

This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt to map anger and its components (i.e., physiological, cognitive, experiential) to the neuroscience literature (i.e., genetic markers, functional imaging of human brain networks) and to linguistic expressions used to describe anger feelings. Given the ubiquity of anger in both its normative and chronic states, specific language is used in humans to express states of anger. Following a review of the neuroscience literature, we explore the language that is used to convey angry feelings, as well as metaphors reflecting inner states of anger experience. We then discuss whether these linguistic expressions can be mapped on to the neural circuits during anger experience and to distinct components of anger. We also identify relationships between anger components, brain networks, and other affective research relevant to motivational states of dominance and basic needs for safety

Defining clinical characteristics of emotion dysregulation in bipolar disorder: A systematic review and meta-analysis

Emotion dysregulation (ED) is characterized by rigid and frequent use of maladaptive emotion regulation (ER) strategies. Conceptualized as a transdiagnostic feature, ED may occur in both clinical and non-clinical populations, including people diagnosed with bipolar disorder (BD) and their first-degree relatives (FDRs), though expected to manifest with differential clinical features. To this end, we conducted a systematic review and meta-analysis of the literature comparing people with BD to healthy controls (HCs) or FDRs, from inception up to November 25, 2021, across major databases. Random-effects meta-analyses considered twenty-eight studies assessing ER/ED with a validated scale. Patients with BD differed from HCs in adopting more maladaptive ER strategies, such as rumination, risk-taking behaviors, negative focus, and less adaptive ones. Unaffected FDRs differed from people with BD, yet to a lower extent, suggesting that ED may span a continuum. ED in BD should be widely explored to better understand its course and management, with specific interventions aimed at reducing its burden on both high-risk and full-threshold populations