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Markers of Brain Connectivity and Sleep-Dependent Restoration: Basic Research and Translation into Clinical Populations


Jaramillo, Valeria. Markers of Brain Connectivity and Sleep-Dependent Restoration: Basic Research and Translation into Clinical Populations. 2020, ETH Zurich.

Abstract

The human brain is a heavily interconnected structure giving rise to complex functions. While brain functionality is mostly revealed during wakefulness, the sleeping brain might offer another view into physiological and pathological brain connectivity. Furthermore, there is a large body of evidence supporting that sleep mediates plastic changes in brain connectivity. Although brain plasticity depends on environmental input which is provided in the waking state, disconnection during sleep might be necessary for integrating new into existing information and at the same time restoring brain efficiency. The analysis of sleep-dependent restoration therefore may provide additional insight into the mechanisms underlying healthy and altered brain function. The overarching aim of this thesis was to examine alterations in markers of brain connectivity and sleep-dependent restoration in clinical populations. To this end, we first evaluated structural, molecular, and electrophysiological markers of brain connectivity and sleep-dependent restoration using Magnetic Resonance Imaging and electroencephalography in a healthy population. More specifically, this was carried out in the framework of healthy brain development, as this time window is characterized by major changes in brain connectivity and plasticity and therefore represents an ideal setting to test these markers. In a second step, we translated the gained findings into two clinical populations in which alterations in brain connectivity have been described, the neuropsychiatric disorder attention-deficit/hyperactivity disorder (ADHD) and the neurologic disorder thalamic ischemic stroke.

Results of the first part validated previously established markers of brain connectivity. These included the structural marker gray matter volume, the electrophysiological markers slow wave activity (SWA) and slow wave slope, and the molecular marker glutamate + glutamine (GLX). In addition, the decrease of SWA and slow wave slope across the night were confirmed as markers for sleep-dependent restoration. Although overnight GLX changes seemed a promising marker for sleep-dependent restoration in healthy young adults, this was not confirmed in healthy children and adolescents. In the second part, we demonstrated alterations in SWA and overnight slope changes in ADHD and in thalamic ischemic stroke. Moreover, these markers were shown to be linked to core symptoms in the investigated disorders.

Taken together, our results indicate that SWA and overnight slope changes constitute promising biomarkers to assess alterations in brain connectivity and sleep-dependent restoration in clinical populations. Furthermore, these findings provide valuable insight into the mechanisms of pathophysiology in ADHD and in thalamic ischemic stroke. Finally, this data suggests a bi-directional relationship between brain connectivity and sleep-dependent restoration which needs to be investigated further in future studies.

Abstract

The human brain is a heavily interconnected structure giving rise to complex functions. While brain functionality is mostly revealed during wakefulness, the sleeping brain might offer another view into physiological and pathological brain connectivity. Furthermore, there is a large body of evidence supporting that sleep mediates plastic changes in brain connectivity. Although brain plasticity depends on environmental input which is provided in the waking state, disconnection during sleep might be necessary for integrating new into existing information and at the same time restoring brain efficiency. The analysis of sleep-dependent restoration therefore may provide additional insight into the mechanisms underlying healthy and altered brain function. The overarching aim of this thesis was to examine alterations in markers of brain connectivity and sleep-dependent restoration in clinical populations. To this end, we first evaluated structural, molecular, and electrophysiological markers of brain connectivity and sleep-dependent restoration using Magnetic Resonance Imaging and electroencephalography in a healthy population. More specifically, this was carried out in the framework of healthy brain development, as this time window is characterized by major changes in brain connectivity and plasticity and therefore represents an ideal setting to test these markers. In a second step, we translated the gained findings into two clinical populations in which alterations in brain connectivity have been described, the neuropsychiatric disorder attention-deficit/hyperactivity disorder (ADHD) and the neurologic disorder thalamic ischemic stroke.

Results of the first part validated previously established markers of brain connectivity. These included the structural marker gray matter volume, the electrophysiological markers slow wave activity (SWA) and slow wave slope, and the molecular marker glutamate + glutamine (GLX). In addition, the decrease of SWA and slow wave slope across the night were confirmed as markers for sleep-dependent restoration. Although overnight GLX changes seemed a promising marker for sleep-dependent restoration in healthy young adults, this was not confirmed in healthy children and adolescents. In the second part, we demonstrated alterations in SWA and overnight slope changes in ADHD and in thalamic ischemic stroke. Moreover, these markers were shown to be linked to core symptoms in the investigated disorders.

Taken together, our results indicate that SWA and overnight slope changes constitute promising biomarkers to assess alterations in brain connectivity and sleep-dependent restoration in clinical populations. Furthermore, these findings provide valuable insight into the mechanisms of pathophysiology in ADHD and in thalamic ischemic stroke. Finally, this data suggests a bi-directional relationship between brain connectivity and sleep-dependent restoration which needs to be investigated further in future studies.

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Additional indexing

Item Type:Dissertation (cumulative)
Referees:Wenderoth Nicole, Huber Reto, Baumann Christian
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2020
Deposited On:25 Jan 2021 14:21
Last Modified:25 Jan 2021 14:21
OA Status:Closed
Publisher DOI:https://doi.org/10.3929/ethz-b-000449765

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