Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review.

OBJECTIVE: This systematic review aims to synthesise and evaluate structural MRI (sMRI) and functional MRI (fMRI) studies in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). METHODS: We systematically searched Medline and Ovid and included articles from 1991 (date of Oxford diagnostic criteria for CFS/ME) to first April 2019. Studies were selected by predefined inclusion and exclusion criteria. Two reviewers independently reviewed the titles and abstracts to determine articles for inclusion, full text and quality assessment for risk of bias. RESULTS: sMRI studies report differences in CFS/ME brain anatomy in grey and white matter volume, ventricular enlargement and hyperintensities. Three studies report no neuroanatomical differences between CFS/ME and healthy controls. Task-based fMRI investigated working memory, attention, reward and motivation, sensory information processing and emotional conflict. The most consistent finding was CFS/ME exhibited increased activations and recruited additional brain regions. Tasks with increasing load or complexity produced decreased activation in task-specific brain regions. CONCLUSIONS: There were insufficient data to define a unique neural profile or biomarker of CFS/ME. This may be due to inconsistencies in finding neuroanatomical differences in CFS/ME and the variety of different tasks employed by fMRI studies. But there are also limitations with neuroimaging. All brain region specific volumetric differences in CFS/ME were derived from voxel-based statistics that are biased towards group differences that are highly localised in space. fMRI studies demonstrated both increases and decreases in activation patterns in CFS/ME, this may be related to task demand. However, fMRI signal cannot differentiate between neural excitation and inhibition or function-specific neural processing. Many studies have small sample sizes and did not control for the heterogeneity of this clinical population. We suggest that with robust study design, subgrouping and larger sample sizes, future neuroimaging studies could potentially lead to a breakthrough in our understanding of the disease

Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.

Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required

Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review

Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS

Identification of neurobiological mechanisms associated with attention deficits in adults post traumatic brain injury

Traumatic Brain Injury (TBI) is one of the major public health concerns with approximately 70 million new cases occurring worldwide per year. It is often caused by a forceful bump, blow, or jolt to the head, resulting in brain tissue damage and normal brain functions disruption. All grades of TBI, ranging from mild to severe, can cause wide-ranging and long-term effects on affected individuals, resulting in physical impairments, and neurocognitive consequences that permanently affect their abilities to perform daily activities. Attention deficits are the most common persisting neurocognitive consequences following TBI, which significantly contribute to poor academic and social functioning, and life-long learning difficulties of affected individuals. However, attention deficits have been evaluated and treated based on symptom endorsements from subjective observations, with few therapeutic interventions successfully translated to the clinic. The consensus regarding appropriate evaluation and treatment of TBI induced attention deficits in this cohort is rather limited due to the lack of investigations of the neurobiological substrates associated with this syndrome. The overall aim of this dissertation research is to systematically investigate the neurobiological mechanisms associated with attention deficits in adults post TBI by utilizing multiple powerful neuroimaging techniques including the functional near-infrared spectroscopy (fNIRS) and multimodal magnetic resonance imaging (MRI), with an ultimate goal of translating hypothesis-driven neurobiological correlates into the quantitatively measurable biomarkers for diagnosis of TBI-induced attention deficits and development of more refined long-term treatment and intervention strategies. This dissertation research is conducted through three specific projects. Project 1 focuses on the investigation of brain functional patterns including the regional cortical brain activation and between-regional pairwise functional connectivity responding to visual sustained attention processing in individuals with and without TBI, by utilizing the fNIRS technique. Project 2 continues the examination of brain functional patterns by assessing the whole brain network topological properties responding to visual sustained attention processing in a larger sample of individuals with and without TBI, by utilizing the functional MRI technique and a graph theoretic approach. Project 3, on the other hand, investigates the brain structural characteristics based on the same sample involved in Project 2, by utilizing the structural MRI and diffusion tensor imaging techniques. For all these three projects, the differences of these brain imaging measures are compared between the groups of TBI and control. Correlation analyses are further conducted between those brain imaging measures which shows significant between-group differences and attention-related behaviors. In addition, Project 3 additionally investigates gender-specific patterns of the altered brain structural properties in TBI patients, relative to controls. The outcome of this novel and valuable dissertation research may shed light on the neural mechanisms of attention deficits in adults post TBI, and may suggest the neurobiological targets for treatment of this severe and common condition. It may also provide important neural foundation for future research to develop effective rehabilitation strategies to improve attention processing in adults post TBI

Unexpected reductions in regional cerebral perfusion during prolonged hypoxia

KEY POINTS: Cognitive performance is impaired by hypoxia despite global cerebral oxygen delivery and metabolism being maintained. Using arterial spin labelled (ASL) magnetic resonance imaging, this is the first study to show regional reductions in cerebral blood flow (CBF) in response to decreased oxygen supply (hypoxia) at 2 h that increased in area and became more pronounced at 10 h. Reductions in CBF were seen in brain regions typically associated with the ‘default mode’ or ‘task negative’ network. Regional reductions in CBF, and associated vasoconstriction, within the default mode network in hypoxia is supported by increased vasodilatation in these regions to a subsequent hypercapnic (5% CO(2)) challenge. These results suggest an anatomical mechanism through which hypoxia may cause previously reported deficits in cognitive performance. ABSTRACT: Hypoxia causes an increase in global cerebral blood flow, which maintains global cerebral oxygen delivery and metabolism. However, neurological deficits are abundant under hypoxic conditions. We investigated regional cerebral microvascular responses to acute (2 h) and prolonged (10 h) poikilocapnic normobaric hypoxia. We found that 2 h of hypoxia caused an expected increase in frontal cortical grey matter perfusion but unexpected perfusion decreases in regions of the brain normally associated with the ‘default mode’ or ‘task negative’ network. After 10 h in hypoxia, decreased blood flow to the major nodes of the default mode network became more pronounced and widespread. The use of a hypercapnic challenge (5% CO(2)) confirmed that these reductions in cerebral blood flow from hypoxia were related to vasoconstriction. Our findings demonstrate steady‐state deactivation of the default network under acute hypoxia, which become more pronounced over time. Moreover, these data provide a unique insight into the nuanced localized cerebrovascular response to hypoxia that is not attainable through traditional methods. The observation of reduced perfusion in the posterior cingulate and cuneal cortex, which are regions assumed to play a role in declarative and procedural memory, provides an anatomical mechanism through which hypoxia may cause deficits in working memory

Cerebellar contribution to Cognitive Impairment in early stages of Relapsing-Remitting Multiple Sclerosis: a conventional and rs-fMRI study

Background. The cerebellum is a primary site of Multiple Sclerosis (MS) pathology. Structural and functional MRI studies have demonstrated the role of the posterior cerebellum in cognitive functions. To date, the “Cerebellar Cognitive Affective Syndrome” (CCAS) scale has never been used to test MS-related Cognitive Impairment (CI) and its association with cerebellar involvement. Objectives. We investigated the association of MRI structural and functional abnormalities of the cognitive cerebellum with CI and tested the role of the CCAS scale in detecting CI in a cohort of very early RRMS patients. Methods. 37 patients with early RRMS and 4 age- and sex-matched healthy controls (HC) were enrolled in this cross-sectional, exploratory study. Cognitive performances were assessed through BICAMS, D-KEFS ST, and CCAS scale. Using a CCAS scale score cut-off (based on a 50 HC sample), 26/37 (70%) patients were classified as “Normal-CCAS” and 11/37 (30%) as “Impaired-CCAS”. All subjects underwent a conventional and resting-state functional MRI (rs-fMRI) protocol. Comparisons between groups were assessed for structural and functional MRI parameters. Moreover, correlations between cognitive test scores and structural-functional MRI parameters were evaluated. Results. Patients with pathological score on CCAS also showed CVLT-II and D-KEFS ST low scores. A significant reduction in cerebellar volumetric parameters was found in the CCAS-impaired MS group compared to the normal one, albeit whole brain WM and thalamic volumes were also significantly reduced. The rs-fMRI analysis revealed higher functional connectivity (FC) between the cognitive cerebellum and most of the functional brain cortical networks in the CCAS-impaired group compared to the normal one. Conclusions. Our findings suggest that CI in early RRMS is associated with pathological alterations in both structural and functional MRI parameters. Higher FC between cerebellar-brain networks in CCAS-impaired patients might be the expression of a compensatory hyperactivation of altered cognitive cerebellar connections. Finally, although the CCAS scale has proven able to detect CI in MS patients, its specificity for cerebellar pathology needs to be further investigated

Forebrain neurocircuitry associated with human reflex cardiovascular control

© 2015 Shoemaker and Goswami. Physiological homeostasis depends upon adequate integration and responsiveness of sensory information with the autonomic nervous system to affect rapid and effective adjustments in end organ control. Dysregulation of the autonomic nervous system leads to cardiovascular disability with consequences as severe as sudden death. The neural pathways involved in reflexive autonomic control are dependent upon brainstem nuclei but these receive modulatory inputs from higher centers in the midbrain and cortex. Neuroimaging technologies have allowed closer study of the cortical circuitry related to autonomic cardiovascular adjustments to many stressors in awake humans and have exposed many forebrain sites that associate strongly with cardiovascular arousal during stress including the medial prefrontal cortex, insula cortex, anterior cingulate, amygdala and hippocampus. Using a comparative approach, this review will consider the cortical autonomic circuitry in rodents and primates with a major emphasis on more recent neuroimaging studies in awake humans. A challenge with neuroimaging studies is their interpretation in view of multiple sensory, perceptual, emotive and/or reflexive components of autonomic responses. This review will focus on those responses related to non-volitional baroreflex control of blood pressure and also on the coordinated responses to non-fatiguing, non-painful volitional exercise with particular emphasis on the medial prefrontal cortex and the insula cortex

Forebrain neurocircuitry associated with human reflex cardiovascular control.

Physiological homeostasis depends upon adequate integration and responsiveness of sensory information with the autonomic nervous system to affect rapid and effective adjustments in end organ control. Dysregulation of the autonomic nervous system leads to cardiovascular disability with consequences as severe as sudden death. The neural pathways involved in reflexive autonomic control are dependent upon brainstem nuclei but these receive modulatory inputs from higher centers in the midbrain and cortex. Neuroimaging technologies have allowed closer study of the cortical circuitry related to autonomic cardiovascular adjustments to many stressors in awake humans and have exposed many forebrain sites that associate strongly with cardiovascular arousal during stress including the medial prefrontal cortex, insula cortex, anterior cingulate, amygdala and hippocampus. Using a comparative approach, this review will consider the cortical autonomic circuitry in rodents and primates with a major emphasis on more recent neuroimaging studies in awake humans. A challenge with neuroimaging studies is their interpretation in view of multiple sensory, perceptual, emotive and/or reflexive components of autonomic responses. This review will focus on those responses related to non-volitional baroreflex control of blood pressure and also on the coordinated responses to non-fatiguing, non-painful volitional exercise with particular emphasis on the medial prefrontal cortex and the insula cortex