The Brain-Gut-Microbiome Axis.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases

The autonomic brain: multi-dimensional generative hierarchical modelling of the autonomic connectome

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods — and data scales — hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system — a multidimensional, generative network — that renders its richness tractable within future models of its function in health and disease

The autonomic brain: Multi-dimensional generative hierarchical modelling of the autonomic connectome.

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods-and data scales-hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system-a multidimensional, generative network-that renders its richness tractable within future models of its function in health and disease

Neuroanatomical Distribution of Neurons within the Hypothalamic Paraventricular Nucleus that Project to the Brainstem Rostral Ventrolateral Medulla

The sympathetic nervous system is important in maintaining cardiovascular homeostasis. Elevated cardiovascular-related sympathetic activity can lead to neurogenic hypertension and a host of other serious cardiac-related abnormalities. The paraventricular nucleus (PVN) of the hypothalamus plays an important role in sympathetic cardiovascular regulation. Neurons from the PVN project to the rostral ventrolateral medulla (RVLM), which is the main brain stem sympathetic cardiovascular control center. While RVLM-projecting PVN neurons have been well characterized, the topographical organization within the PVN subnuclei is still not fully known. This neuroanatomical study aimed to map the topographical distribution of RVLM-projecting PVN neurons. Four different carboxylate FluoSphereTM retrograde tracers (blue, 365/415; green, 505/515; red, 565/580; and far-red, 660/680) were injected at different rostro-caudal coordinates within the RVLM. The vast majority of RVLM-projecting PVN neurons were ipsilateral and located in the medial parvocellular subnucleus. Whereas most neurons were ipsilateral, there is a small fraction of neurons that crossed the midline. RVLM-projecting neurons were also identified within the dorsal, ventral, and posterior parvocellular subnuclei of the PVN with no labeling found in the anterior parvocellular or magnocellular subnuclei. Additionally, we observed different efficiencies of the retrograde tracers with blue (365/415) being the least efficient and red (565/580) being the best. These neuroanatomical data will serve as important preliminary data for future research investigating the functional and histochemical properties of these PVN neurons

Improving the Assessment and Understanding of Neurogenic Orthostatic Hypotension

Neurogenic Orthostatic Hypotension (NOH) is a cardinal feature of autonomic failure. Patients with NOH experience a persistent and consistent drop in blood pressure when standing due to failure of the autonomic nervous system to reflexively increase sympathetic outflow. NOH affects individuals worldwide, presenting as both a primary feature (i.e. Multiple Systems Atrophy, Pure Autonomic Failure) and secondary to several common disorders including diabetes and Parkinson’s Disease. However, there are still several gaps in our overall understanding and assessment of patients with NOH. Therefore, the six studies presented in this thesis aimed to address some of these gaps in our current knowledge. Study 1 and 2 aimed to investigate activity within the central autonomic network (CAN) both at rest and during standardized autonomic challenges to determine whether patients have reduced activity relative to healthy controls. In this study we found patients had reduced activation in several CAN structures including the cingulate cortices, thalamus, hippocampus and cerebellum. Based on study 1 and 2 results, study 3 and 4 aimed to determine whether patients also had reduced functional connectivity in two structures involved in postural blood pressure regulation: the brainstem and cerebellum. We found patients had significantly less connectivity between the brainstem and several CAN structures including the cerebellum, insula and cingulate cortices. Additionally, patients had significantly less intracerebellar connectivity, less cerebellar-brainstem connectivity and reduced connectivity to CAN structures including the insula, anterior cingulate, hippocampus, thalamus and putamen. Finally, symptoms associated with NOH include postural light-headedness, dizziness and syncope. Proper diagnosis rests in the ability to accurately distinguish these non-specific symptoms as either orthostatic (postural) or non-orthostatic (non-postural). The purposes of studies 5 and 6 were to create a simple instrument capable of making this distinction, demonstrate its validity and reliability, sensitivity and specificity, and to test its ability to assess individuals based on symptomatology. In these studies, I found our questionnaire was valid, reliable and capable of positively predicting individuals with orthostatic intolerance related to autonomic dysfunction. Overall, this thesis greatly expands our understanding of NOH pathophysiology and provides a new tool for assessing orthostatic symptomatology related to autonomic dysfunction

Brain Resilience: Shedding Light into the Black Box of Adventure Processes

Understanding of the active beneficial processes of adventure learning remains elusive. Resilience may provide one foundation for understanding the positive adaptation derived from Outdoor Adventure Education (OAE) and Adventure Therapy (AT) programming. From a neurological perspective, resilience may be explained by the brain’s innate capability to adapt its structure (growth of new cells) and function (re-wiring of existing cells) directly in response to environmental exposure. This paper explores the role of known brain responses to experiences analogous to adventure programming based on themes from a key literature review. The fundamental paradigm of ‘stress and recovery’ contends that a balance of neurobiological processes help realign psychosocial equilibrium in the short term and over time. Through progressive, repeated exposure to custom-built outdoor challenges, the concept of brain resilience may provide a scientific platform for understanding the mechanisms of achieving meaningful, authentic and healthy outcomes. It could also help to begin to illuminate a section of the black box of adventure processes

Recording and quantifying sympathetic outflow to muscle and skin in humans : methods, caveats and challenges

The development of microneurography, in which the electrical activity of axons can be recorded via an intrafascicular microelectrode inserted through the skin into a peripheral nerve in awake human participants, has contributed a great deal to our understanding of sensorimotor control and the control of sympathetic outflow to muscle and skin. This review summarises the different approaches to recording muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), together with discussion on the issues that determine the quality of a recording. Various analytical approaches are also described, with a primary emphasis on those developed by the author, aimed at maximizing the information content from recordings of postganglionic sympathetic nerve activity in awake humans

Why Blood Pressure and Body Mass Should be Controlled for in Resting-State Functional Magnetic Resonance Imaging Studies

Masteroppgave i psykologiMAPSYK360INTL-PSYKINTL-HFINTL-JUSINTL-MEDINTL-KMDMAPS-PSYKINTL-SVINTL-M