Tired of being tired:Fatigue and sleep following traumatic brain injury

In the disease processes following all severities of acquired brain injury, fatigue and sleep disturbances are highly prevalent and may last from the initial recovery phase up until years post-injury. Furthermore, these symptoms are associated with poorer social, physical, cognitive, and general functioning. This leads to reduced capacity for performing activities such as work, studying, leisure activities, and less functional independence and social relationships. Where do these complaints come from and which factors go hand in hand with these complaints? This dissertation investigated the behavioural and neuronal underpinnings and associated factors of fatigue and sleep problems after traumatic brain injury. A better understanding of the underlying factors associated with fatigue and sleep disturbances might aid the development of new treatments aimed at reducing fatigue and sleep disturbances following brain injury

Drug and disease effects on the human brain studied by functional MRI

Background: With the advent of magnetic resonance imaging (MRI) technology, various functional MRI (fMRI) techniques have become available for non-invasive neuroscientific studies and clinical diagnostics, which have led to a better understanding of the human brain function in normal and diseased subjects. In order to interpret the fMRI results correctly and design optimal research studies it is important to understand both the potentials and limitations associated with each fMRI technique. In this thesis we used two fMRI techniques: arterial spin labeling (ASL) and resting-sate BOLD (blood-oxygen-level dependent) fMRI to study the effects of a CNS-active (central nervous system) drug and neurologic disorder on the human brain function. Purpose: The main research purposes of this thesis are the following: 1) We assess the reproducibility and reliability of rCBF (regional cerebral blood flow) measurements conducted at 3T with pCASL (pseudo continuous ASL) technique; 2) We study the pharmacokinetics of a CNS active drug in normal volunteers by conducting rCBF measurements as a function of time after intake of a single dose of 20 mg d-amphetamine with the pCASL technique; 3) We investigate the possible neurological abnormalities of mild traumatic brain injury (mTBI) patients with chronic fatigue by performing rCBF and resting-sate functional connectivity measurements before, during and after a 20 minute continuous psychomotor vigilance task (PVT). Conclusion: The results from these studies show that the pCASL technique is a relatively robust method for quantitative measurements of rCBF in both normal volunteers and patient subjects. Repeated rCBF measurements with the pCASL method is a non-invasive and sufficiently sensitive approach to assess pharmacokinetic response to CNS active chemicals and should be useful for studying the neurophysiological characteristics in vivo of potential CNS drugs. The results from the mTBI subjects demonstrate that the repeated measurements of rCBF and functional connectivity metrics before, during and after a PVT provide sensitive diagnostic imaging methods to assess neurological abnormality of mTBI patients without apparent neuroanatomical damage. In addition to the clinical diagnostic value, these studies also contribute to important knowledge for the design and analysis of brain functional imaging studies of drugs and neurological diseases

Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction

The Neurobiology of Pathological Fatigue: New Models, New Questions

The last decade has seen the emergence of new theoretical frameworks to explain pathological fatigue, a much neglected, yet highly significant symptom across a wide range of diseases. While the new models of fatigue provide new hypotheses to test, they also raise a number of questions. The primary purpose of this essay is to examine the predictions of three recently proposed models of fatigue, the overlap and differences between them, and the evidence from diseases that may lend support to the models of fatigue. I also present expansions for the sensory attenuation model of fatigue. Further questions examined here are the following: What are the neural substrates of fatigue? How can sensory attenuation, which underpins agency also explain fatigue? Are fatigue and agency related

Neuroplastic effects in patients with traumatic brain injury after music-supported therapy

Source at https://doi.org/10.3389/fnhum.2019.00177.Damage to the orbitofrontal cortex (OFC) often occurs following a traumatic brain injury (TBI) and can lead to complex behavioral changes, including difficulty with attention and concentration. We investigated the effects of musical training on patients with behavioral and cognitive deficits following a mild traumatic brain injury (mTBI) and found significant functional neuro-plastic changes in the OFC’s networks. The results from neuropsychological tests revealed an improved cognitive performance. Moreover, six out of seven participants in this group returned to work post intervention and reported improved well-being and social behavior. In this study, we explore the functional changes in OFC following music-supported intervention in reference to connecting networks that may be responsible for enhanced social interaction. Furthermore, we discuss the factor of dopamine release during playing as an element providing a possible impact on the results. The intervention consisted of playing piano, two sessions per week in 8 weeks, 30 min each time, with an instructor. Additional playing was required with a minimum of 15 min per day at home. Mean time playing piano in reference to participant’s report was 3 h per week during the intervention period. Three groups participated, one mTBI group (n = 7), two control groups consisting of healthy participants, one with music training (n = 11), and one baseline group without music training (n = 12). Participants in the clinical group had received standardized cognitive rehabilitation treatment during hospitalization without recovering from their impairments. The intervention took place 2 years post injury. All participants were assessed with neuropsychological tests and with both task and resting-state functional magnetic resonance imaging (fMRI) pre-post intervention. The results demonstrated a significant improvement of neuropsychological tests in the clinical group, consistent with fMRI results in which there were functional changes in the orbitofrontal networks (OFC). These changes were concordantly seen both in a simple task fMRI but also in resting-state fMRI, which was analyzed with dynamic causal modeling (DCM). We hypothesized that playing piano, as designed in the training protocol, may provide a positive increase in both well-being and social interaction. We suggest that the novelty of the intervention may have clinical relevance for patients with behavioral problems following a TBI

Effects of Music Training on Cortical Plasticity: : Cognitive Rehabilitation of Patients with Traumatic Brain Injury

The aim of this thesis was to explore the neuroplastic effects of playing the piano on patients with cognitive impairment following a mild traumatic brain injury (mTBI). It was hypothesised that playing the piano would stimulate neural networks to re-route neural connections and link up cortical circuits that had been functionally inhibited due to minor disruption of brain tissue. The objective of the intervention was to restore the patients’ cognitive processing to pre-injury levels. The study was designed as a pilot study with three experimental groups: (1) 7 patients with cognitive deficits following mTBI two years post-injury (Group 1), (2) 11 healthy subjects (Group 2), and (3) 12 further healthy subjects (Group 3). A between-group design and a longitudinal (pre-post-intervention) within-subject design were applied. Groups 1 and 2 were given eight weeks of piano training. A combination of cognitive and functional neuroimaging (task-based and resting-state fMRI) in addition to neuropsychological tests were performed pre- and post-intervention for all three groups. The results concurrently demonstrated in two independent analyses and fMRI datasets that longitudinal changes in functional connectivity took place within the orbitofrontal cortex (OFC) in the mTBI patient group only, showing increased connectivity between the OFC regions post-intervention involved in executive functions (EF), social cognition and emotional regulation. This finding provides support for the contribution of the OFC as a key mechanism that potentially drives the cognitive benefit of piano training in TBI, and further suggests a network of other connected frontal regions that may be linked to this. The key findings of this study could suggest a causal relationship between musical training and a functional reorganisation of neural networks that promotes enhanced cognitive performance. These results might hold promise as regards adding a novel music-based intervention to the cognitive rehabilitation of mTBI patients.Doktorgradsavhandlin

Identification and neuromodulation of brain states to promote recovery of consciousness

Experimental and clinical studies of consciousness identify brain states (i.e., transient, relevant features of the brain associated with the state of consciousness) in a non-systematic manner and largely independent from the research into the induction of state changes. In this narrative review with a focus on patients with a disorder of consciousness (DoC), we synthesize advances on the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anesthesia) and pathological (DoC) states of altered consciousness in human. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication in the brain is sparser, less efficient, and less complex. The results also highlight damaged resting state networks, in particular the default mode network, decreased connectivity in long-range connections and in the thalamocortical loops. Next, we show that therapeutic approaches to treat DoC, through pharmacology (e.g., amantadine, zolpidem), and (non-)invasive brain stimulation (e.g., transcranial current stimulation, deep brain stimulation) have shown some effectiveness to promote consciousness recovery. It seems that these deteriorated features of conscious brain states may improve in response to these neuromodulation approaches, yet, targeting often remains non-specific and does not always lead to (behavioral) improvements. Furthermore, in silico model-based approaches allow the development of personalized assessment of the effect of treatment on brain-wide dynamics. Although still in infancy, the fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when united, might propel the development of new and better targeted techniques for DoC. For example, brain states could be identified in a predictive setting, and the theoretical and empirical testing (i.e., in animals, under anesthesia and patients with a DoC) of neuromodulation techniques to promote consciousness could be investigated. This review further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multi-modal and multi-species approaches outlined throughout the review. This paper presents interactive figures, supported by the Live Paper initiative of the Human Brain Project, enabling the interaction with data and figures illustrating the concepts in the paper through EBRAINS (go to https://wiki.ebrains.eu/bin/view/Collabs/live-paper-states-altered-consciousness and get started with an EBRAINS account).NA is research fellow, OG is Research Associate, and SL is research director at FRS-FNRS. JA is postdoctoral fellow at the FWO. The study was further supported by the University and University Hospital of Liège, the BIAL Foundation, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), the FNRS PDR project (T.0134.21), the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project), the fund Generet, the King Baudouin Foundation, the Télévie Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Public Utility Foundation 'Université Européenne du Travail', "Fondazione Europea di Ricerca Biomedica", the BIAL Foundation, the Mind Science Foundation, the European Commission, the Fondation Leon Fredericq, the Mind-Care foundation, the DOCMA project (EU-H2020-MSCA–RISE–778234), the National Natural Science Foundation of China (Joint Research Project 81471100) and the European Foundation of Biomedical Research FERB Onlus