EEG amplitude modulation analysis for semi-automated diagnosis of Alzheimer's disease

Recent experimental evidence has suggested a neuromodulatory deficit in Alzheimer's disease (AD). In this paper, we present a new electroencephalogram (EEG) based metric to quantitatively characterize neuromodulatory activity. More specifically, the short-term EEG amplitude modulation rate-of-change (i.e., modulation frequency) is computed for five EEG subband signals. To test the performance of the proposed metric, a classification task was performed on a database of 32 participants partitioned into three groups of approximately equal size: healthy controls, patients diagnosed with mild AD, and those with moderate-to-severe AD. To gauge the benefits of the proposed metric, performance results were compared with those obtained using EEG spectral peak parameters which were recently shown to outperform other conventional EEG measures. Using a simple feature selection algorithm based on area-under-the-curve maximization and a support vector machine classifier, the proposed parameters resulted in accuracy gains, relative to spectral peak parameters, of 21.3% when discriminating between the three groups and by 50% when mild and moderate-to-severe groups were merged into one. The preliminary findings reported herein provide promising insights that automated tools may be developed to assist physicians in very early diagnosis of AD as well as provide researchers with a tool to automatically characterize cross-frequency interactions and their changes with disease

Early diagnosis of Alzheimer's disease: the role of biomarkers including advanced EEG signal analysis. Report from the IFCN-sponsored panel of experts

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD

Neurophysiological and brain structural markers of cognitive frailty differs from Alzheimer’s disease

AbstractWith increasing life span, there is growing importance of understanding the mechanisms of successful cognitive ageing. In contrast, cognitive frailty has been proposed to be a precursor to Alzheimer’s disease. Here we test the hypothesis that cognitively frail adults represent a branch of healthy ageing, distinct from latent dementia. We used electro-magnetoencephalography and magnetic resonance imaging to investigate the structural and neurophysiological features of cognitive frailty in relation to healthy aging, and clinical presentations of mild cognitive impairment and Alzheimer’s disease. Cognitive performance of the cognitively frail group was similar to those with mild cognitive impairment. We used a novel cross-modal oddball task to induce mismatch responses to unexpected stimuli. Both controls and cognitively frail showed stronger mismatch responses and larger temporal grey matter volume, compared to people with mild cognitive impairment and Alzheimer’s disease. Our results suggest that cognitively frail represents a spectrum of normal ageing rather than incipient or undiagnosed Alzheimer’s disease. Lower cognitive reserve, hearing impairment and medical comorbidity might contribute to the aetiology of cognitive impairment.The study was supported by the Medical Research Council [SUAG/004 RG91365, SUAG/046 RG101400; SUAG/051 RG101400], the Wellcome Trust [103838], the Dementias Platform UK [MR/L023784/1 & MR/L023784/2], Alzheimer’s Research UK [ARUK-PG2017B-19], a Holt Fellowship, and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission

Etude expérimentale des dynamiques temporelles du comportement normal et pathologique chez le rat et la souris

155 p.Modern neuroscience highlights the need for designing sophisticated behavioral readout of internal cognitive states. From a thorough analysis of classical behavioral test, my results supports the hypothesis that sensory ypersensitivity might be the cause of other behavioural deficits, and confirm the potassium channel BKCa as a potentially relevant molecular target for the development of drug medication against Fragile X Syndrome/Autism Spectrum Disorders. I have also used an innovative device, based on pressure sensors that can non-invasively detect the slightest animal movement with unprecedented sensitivity and time resolution, during spontaneous behaviour. Analysing this signal with sophisticated computational tools, I could demonstrate the outstanding potential of this methodology for behavioural phenotyping in general, and more specifically for the investigation of pain, fear or locomotion in normal mice and models of neurodevelopmental and neurodegenerative disorders

Investigating attentional function and cognitive fluctuations in Lewy body dementia

PhD ThesisLewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), are characterised by attentional dysfunction and fluctuating cognition. The underlying aetiology of these clinical features is poorly understood, yet such knowledge is essential for developing effective management strategies. The aim of this project was to determine the specific facets of attention affected in LBD patients, and to use high-density electroencephalography (EEG) to delineate the underlying pathophysiology and how this relates to cognitive fluctuations. Methods: Attentional network efficiency was investigated in LBD patients (n = 32), Alzheimer’s disease (AD) patients (n = 27), and age-matched healthy controls (n = 21) by using a modified version of the Attention Network Test (ANT). The ANT, a visual attention task, probes the efficiency of three anatomically defined attentional networks: alerting, orienting and executive conflict. Participants completed the ANT whilst undergoing EEG recordings (128 channels). In a subsample of the participants (22 DLB, 24 AD, 19 controls), time-frequency wavelet analyses were conducted to investigate event-related spectral perturbations (ERSP), between 4-90 Hz, in the 500 ms post-stimuli presentation. Attentional network ERSP was calculated by contrasting the oscillatory reactivity following relevant stimuli. Results: Overall mean reaction time was slower in the dementia groups (AD and LBD) relative to the controls, and the LBD group were slower than the AD group. Behaviourally, there were no group differences regarding the orienting effect. However, both dementia groups exhibited reduced executive conflict processing efficiency, and a lack of an alerting effect. Electrophysiologically, the DLB group exhibited a profound lack of post-stimulus oscillatory reactivity below 30 Hz, irrespective of stimulus condition. For the alerting network, the DLB group exhibited attenuated reactivity in the lower frequencies (< 30 Hz); in the theta range (4-7 Hz) the controls and AD group showed global synchronisation (across all regions), peaking at approximately 300 ms, which was absent in the DLB group. Lack of DLB theta synchronisation between 200-450 ms over the right parietal cortex was associated with a ii higher total score on the Clinical Assessment of Fluctuation scale. Orienting and executive conflict network reactivity was comparable across all groups; primarily intermittent synchronisation, of reduced power relative to the alerting network, diffuse across the time and frequency domains in all regions. Conclusions: Attenuated global oscillatory reactivity in the DLB group specific to the alerting network (the network associated with the ability to maintain an alert state) is indicative of this fractionated aspect of attention being differentially affected in the DLB patients relative to the AD and control groups. Lack of theta reactivity in the parietal regions may contribute to the underlying pathophysiology of cognitive fluctuations in DLB.Alzheimer’s Research U

2013 IMSAloquium, Student Investigation Showcase

This year, we are proudly celebrating the twenty-fifth anniversary of IMSA’s Student Inquiry and Research (SIR) Program. Our first IMSAloquium, then called Presentation Day, was held in 1989 with only ten presentations; this year we are nearing two hundred.https://digitalcommons.imsa.edu/archives_sir/1005/thumbnail.jp

Hippocampal glutamatergic/NMDA receptor functioning in bipolar disorder: a combined MMN and 1H-MRS study

Disturbances in the hippocampal glutamate (Glu)/N-methyl-d-aspartate (NMDA) system have been implicated in the pathophysiology of bipolar disorder (BD). Here we aim to provide a targeted integration of two measures of glutamatergic functioning in BD; the association between mismatch negativity (MMN) and in vivo hippocampal-Glu measured via proton magnetic resonance spectroscopy ((1)H MRS). Participants comprised of 33 patients with BD and 23 matched controls who underwent a two-tone passive, duration deviant MMN paradigm and (1)H MRS. Levels of Glu/creatine (Cr) in the hippocampus were determined. Pearson's correlations were used to determine associations between MMN and Glu/Cr. In controls, MMN amplitude was positively associated with Glu/Cr at the left temporal site. We did not find any significant associations with Glu/Cr and frontocentral MMN nor did we find any significant associations in BD patients. The results provide further insight into the neurophysiology of MMN, with evidence supporting the role of hippocampal-Glu signalling through the NMDA receptor in temporal MMN. Our data also demonstrate that Glu/Cr regulation of MMN is dampened in BD, which may indicate a lack of tightly regulated hippocampal NMDA functioning. These findings provide insight into the underlying basis of glutamatergic transmission disturbances implicated in the disorder.NHMRC Australia Fellowship 46491

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician