A Comprehensive Review of Magnetoencephalography (MEG) Studies for Brain Functionality in Healthy Aging and Alzheimer's Disease (AD)

Neural oscillations were established with their association with neurophysiological activities and the altered rhythmic patterns are believed to be linked directly to the progression of cognitive decline. Magnetoencephalography (MEG) is a non-invasive technique to record such neuronal activity due to excellent temporal and fair amount of spatial resolution. Single channel, connectivity as well as brain network analysis using MEG data in resting state and task-based experiments were analyzed from existing literature. Single channel analysis studies reported a less complex, more regular and predictable oscillations in Alzheimer's disease (AD) primarily in the left parietal, temporal and occipital regions. Investigations on both functional connectivity (FC) and effective (EC) connectivity analysis demonstrated a loss of connectivity in AD compared to healthy control (HC) subjects found in higher frequency bands. It has been reported from multiplex network of MEG study in AD in the affected regions of hippocampus, posterior default mode network (DMN) and occipital areas, however, conclusions cannot be drawn due to limited availability of clinical literature. Potential utilization of high spatial resolution in MEG likely to provide information related to in-depth brain functioning and underlying factors responsible for changes in neuronal waves in AD. This review is a comprehensive report to investigate diagnostic biomarkers for AD may be identified by from MEG data. It is also important to note that MEG data can also be utilized for the same pursuit in combination with other imaging modalities

Magnetoencephalography abnormalities in adult mild traumatic brain injury: a systematic review

Background The global incidence of traumatic brain injuries is rising, with at least 80% being classified as mild. These mild injuries are not visible on routine clinical imaging. The potential clinical role of a specific imaging biomarker be it diagnostic, prognostic or directing and monitoring progress of personalised treatment and rehabilitation has driven the exploration of several new neuroimaging modalities. This systematic review examined the evidence for magnetoencephalography (MEG) to provide an imaging biomarker in mild traumatic brain injury (mTBI). Methods Our review was prospectively registered on PROSPERO: CRD42019151387. We searched EMBASE, MEDLINE, trial registers, PsycINFO, Cochrane Library and conference abstracts and identified 37 papers describing MEG changes in mTBI eligible for inclusion. Since meta-analysis was not possible, based on the heterogeneity of reported outcomes, we provide a narrative synthesis of results. Results The two most promising MEG biomarkers are excess resting state low frequency power, and widespread connectivity changes in all frequency bands. These may represent biomarkers with potential for diagnostic application, which reflect time sensitive changes, or may be capable of offering clinically relevant prognostic information. In addition, the rich data that MEG produces are well-suited to new methods of machine learning analysis, which is now being actively explored. Interpretation MEG reveals several promising biomarkers, in the absence of structural abnormalities demonstrable with either computerised tomography or magnetic resonance imaging. This review has not identified sufficient evidence to support routine clinical use of MEG in mTBI currently. However, verifying MEG’s potential would help meet an urgent clinical need within civilian, sports and military medicine

Modelling of the switching behavior of functional connectivity microstates (FCμstates) as a novel biomarker for mild cognitive impairment

It is evident the need for designing and validating novel biomarkers for the detection of mild cognitive impairment (MCI). MCI patients have a high risk of developing Alzheimer’s disease (AD), and for that reason the introduction of novel and reliable biomarkers is of significant clinical importance. Motivated by recent findings about the rich information of dynamic functional connectivity graphs (DFCGs) about brain (dys)function, we introduced a novel approach of identifying MCI based on magnetoencephalographic (MEG) resting state recordings. The activity of different brain rhythms {δ, θ, α1, α2, β1, β2, γ1, γ2} was first beamformed with linear constrained minimum norm variance in the MEG data to determine ninety anatomical regions of interest (ROIs). A dynamic functional connectivity graph (DFCG) was then estimated using the imaginary part of phase lag value (iPLV) for both intra-frequency coupling (8) and also cross-frequency coupling pairs (28). We analysed DFCG profiles of neuromagnetic resting state recordings of 18 Mild Cognitive Impairment (MCI) patients and 20 healthy controls. We followed our model of identifying the dominant intrinsic coupling mode (DICM) across MEG sources and temporal segments that further leads to the construction of an integrated DFCG (iDFCG). We then filtered statistically and topologically every snapshot of the iDFCG with data-driven approaches. Estimation of the normalized Laplacian transformation for every temporal segment of the iDFCG and the related eigenvalues created a 2D map based on the network metric time series of the eigenvalues (NMTSeigs). NMTSeigs preserves the non-stationarity of the fluctuated synchronizability of iDCFG for each subject. Employing the initial set of 20 healthy elders and 20 MCI patients, as training set, we built an overcomplete dictionary set of network microstates (nμstates). Afterward, we tested the whole procedure in an extra blind set of 20 subjects for external validation. We succeeded a high classification accuracy on the blind dataset (85 %) which further supports the proposed Markovian modelling of the evolution of brain states. The adaptation of appropriate neuroinformatic tools that combine advanced signal processing and network neuroscience tools could manipulate properly the non-stationarity of time-resolved FC patterns revealing a robust biomarker for MCI

Translational diagnostic neuroimaging in mild traumatic brain injury and multiple sclerosis

Translation of promising neuroimaging technologies into diagnostic tests requires diagnostic test accuracy studies. This thesis describes two such studies, MEGAbIT and DECISIve. As well as assessing analytical performance, this thesis will attempt to determine the effects of these new technologies on patients and the wider healthcare system. Magnetoencephalography is an imaging technology that is used to study the function of the brain, and as a result provide insight into the acute consequences of mild traumatic brain injury. A systematic literature review and MEGAbIT assessed the diagnostic role of magnetoencephalography in acute mild traumatic brain injury. Head injuries are responsible for 1.4 million visits to UK hospitals annually. Most patients are discharged the same day and make a full recovery, but some will have persistent symptoms. The sensitivity and specificity of magnetoencephalography changes were assessed by including a cohort of non-head acute trauma controls and using a database of healthy controls. The systematic literature review led to excess delta power being selected as the primary outcome for MEGAbIT. MEGAbIT revealed measurement of magnetoencephalography delta power did not differentiate those with mild traumatic brain injury from those with non-head trauma. A pre-specified measure of connectivity did demonstrate a statistically significant group level difference, between those with mild traumatic brain injury and healthy controls, and therefore, warrants further study to explore its diagnostic value. An optimised structural MRI sequence, T2*, has been developed which can demonstrate the perivenular nature of multiple sclerosis inflammatory lesions, the central vein sign, and now needs thorough assessment prior to possible implementation within the NHS. DECISIve assessed the diagnostic role of the T2* MRI sequence, in persons suspected of having multiple sclerosis. Approximately 130 patients are diagnosed with multiple sclerosis each week in the UK. Having an MRI scan is not painful and carries few or no risks, unlike the current alternative of having a lumbar puncture. The aim was to provide the NHS with a test which is more sensitive, safer, cheaper, quicker, and importantly, more acceptable to patients. The DECISIve interim analysis has shown that the sensitivity of the central vein sign is higher than testing for oligoclonal bands by lumbar puncture for the diagnosis of multiple sclerosis. The full DECISIve dataset will have sufficient power to identify a clinically meaningful difference if one exists. The introduction of the central vein sign to the diagnostic pathway of multiple sclerosis is likely to generate cost savings for the NHS, and may positively impact health utility indirectly, by leading to quicker diagnosis and prompter treatment. DECISIve participants have expressed a unanimous preference for MRI scans over undergoing a lumbar puncture. However, for those who do still require lumbar puncture, recommendations have been made to improve the patient experience. This thesis has focussed on translational diagnostic neuroimaging studies. It included a robust diagnostic accuracy study of functional neuroimaging, to help resolve major unanswered scientific questions in mild traumatic brain injury and initiating the first head-to-head comparison of the central vein sign and oligoclonal band testing in the diagnostic pathway of multiple sclerosis

Translational diagnostic neuroimaging in mild traumatic brain injury and multiple sclerosis

Translation of promising neuroimaging technologies into diagnostic tests requires diagnostic test accuracy studies. This thesis describes two such studies, MEGAbIT and DECISIve. As well as assessing analytical performance, this thesis will attempt to determine the effects of these new technologies on patients and the wider healthcare system. Magnetoencephalography is an imaging technology that is used to study the function of the brain, and as a result provide insight into the acute consequences of mild traumatic brain injury. A systematic literature review and MEGAbIT assessed the diagnostic role of magnetoencephalography in acute mild traumatic brain injury. Head injuries are responsible for 1.4 million visits to UK hospitals annually. Most patients are discharged the same day and make a full recovery, but some will have persistent symptoms. The sensitivity and specificity of magnetoencephalography changes were assessed by including a cohort of non-head acute trauma controls and using a database of healthy controls. The systematic literature review led to excess delta power being selected as the primary outcome for MEGAbIT. MEGAbIT revealed measurement of magnetoencephalography delta power did not differentiate those with mild traumatic brain injury from those with non-head trauma. A pre-specified measure of connectivity did demonstrate a statistically significant group level difference, between those with mild traumatic brain injury and healthy controls, and therefore, warrants further study to explore its diagnostic value. An optimised structural MRI sequence, T2*, has been developed which can demonstrate the perivenular nature of multiple sclerosis inflammatory lesions, the central vein sign, and now needs thorough assessment prior to possible implementation within the NHS. DECISIve assessed the diagnostic role of the T2* MRI sequence, in persons suspected of having multiple sclerosis. Approximately 130 patients are diagnosed with multiple sclerosis each week in the UK. Having an MRI scan is not painful and carries few or no risks, unlike the current alternative of having a lumbar puncture. The aim was to provide the NHS with a test which is more sensitive, safer, cheaper, quicker, and importantly, more acceptable to patients. The DECISIve interim analysis has shown that the sensitivity of the central vein sign is higher than testing for oligoclonal bands by lumbar puncture for the diagnosis of multiple sclerosis. The full DECISIve dataset will have sufficient power to identify a clinically meaningful difference if one exists. The introduction of the central vein sign to the diagnostic pathway of multiple sclerosis is likely to generate cost savings for the NHS, and may positively impact health utility indirectly, by leading to quicker diagnosis and prompter treatment. DECISIve participants have expressed a unanimous preference for MRI scans over undergoing a lumbar puncture. However, for those who do still require lumbar puncture, recommendations have been made to improve the patient experience. This thesis has focussed on translational diagnostic neuroimaging studies. It included a robust diagnostic accuracy study of functional neuroimaging, to help resolve major unanswered scientific questions in mild traumatic brain injury and initiating the first head-to-head comparison of the central vein sign and oligoclonal band testing in the diagnostic pathway of multiple sclerosis