Deep Learning of Resting-state Electroencephalogram Signals for 3-class Classification of Alzheimer’s Disease, Mild Cognitive Impairment and Healthy Ageing

Objective. This study aimed to produce a novel deep learning (DL) model for the classification of subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI) subjects and healthy ageing (HA) subjects using resting-state scalp electroencephalogram (EEG) signals. Approach. The raw EEG data were pre-processed to remove unwanted artefacts and sources of noise. The data were then processed with the continuous wavelet transform, using the Morse mother wavelet, to create time-frequency graphs with a wavelet coefficient scale range of 0-600. The graphs were combined into tiled topographical maps governed by the 10-20 system orientation for scalp electrodes. The application of this processing pipeline was used on a data set of resting-state EEG samples from age-matched groups of 52 AD subjects (82.3 ± 4.7 years of age), 37 MCI subjects (78.4 ± 5.1 years of age) and 52 HA subjects (79.6 ± 6.0 years of age). This resulted in the formation of a data set of 16197 topographical images. This image data set was then split into training, validation and test images and used as input to an AlexNet DL model. This model was comprised of five hidden convolutional layers and optimised for various parameters such as learning rate, learning rate schedule, optimiser, and batch size. Main results. The performance was assessed by a tenfold cross-validation strategy, which produced an average accuracy result of 98.9 ± 0.4% for the three-class classification of AD vs MCI vs HA. The results showed minimal overfitting and bias between classes, further indicating the strength of the model produced. Significance. These results provide significant improvement for this classification task compared to previous studies in this field and suggest that DL could contribute to the diagnosis of AD from EEG recordings

Classification of Mild Cognitive Impairment with Deep Transfer Learning Approach using CWT based Scalogram Images

Mild Cognitive Impairment (MCI) is a condition that can occur as a person gets older, and faces problems like recognition, memory, and language skills. Early detection of MCI is crucial, as it can progress to more severe conditions like Alzheimer's disease. This study proposes a method to use Scalogram images, obtained by applying Continuous Wavelet Transform (CWT) to EEG signals and pre-trained models like ResNet50, VGG16, InceptionV3, Inception_ResNetV2 through transfer learning to classify MCI and Healthy Control (HC). Fine-tuning of the models is also used to improve the results, and various performance metrics are employed for classification. The study concludes that Inception_ResNetV2 transfer learning yielded good results, while ResNet50 and InceptionV3 transfer learning with fine-tuning resulted in higher accuracy using a low learning rate

Comparison of resting electroencephalogram coherence in patients with mild cognitive impairment and normal elderly subjects

Mild cognitive impairment (MCI) was a condition beginning before more serious deterioration, leading to Alzheimer’s dementia (AD). MCI detection was needed to determine the patient's therapeutic management. Analysis of electroencephalogram (EEG) coherence is one of the modalities for MCI detection. Therefore, this study investigated the inter and intra-hemispheric coherence over 16 EEG channels in the frequency range of 1-30 Hz. The simulation results showed that most of the electrode pair coherence in MCI patients have decreased compared to normal elderly subjects. In inter hemisphere coherence, significant differences (p<0.05) were found in the FP1-FP2 electrode pairs. Meanwhile, significant differences (p<0.05) were found in almost all pre-frontal area connectivity of the intra-hemisphere coherence pairs. The electrode pairs were FP2-F4, FP2-T4, FP1-F3, FP1-F7, FP1-C3, FP1-T3, FP1-P3, FP1-T5, FP1-O1, F3-O1, and T3-T5. The decreased coherence in MCI patients showed the disconnection of cortical connections as a result of the death of the neurons. Furthermore, the coherence value can be used as a multimodal feature in normal elderly subjects and MCI. It is hoped that current studies may be considered for early detection of Alzheimer’s in a larger population

Reinforcement Learning, Error-Related Negativity, and Genetic Risk for Alzheimer\u27s Disease

Reinforcement learning (RL) has been widely used as a model of animal and human learning and decision-making. The neural networks underlying RL involve many of the same structures primarily affected by Alzheimer’s disease (AD) such as the hippocampus. Yet, RL and non-invasive evaluation of its neural underpinnings have been underutilized as a framework for understanding disease pathology and its pre-clinical states. This study aimed to provide a novel approach for assessing subtle changes in asymptomatic apolipoprotein-E (APOE) carriers and non-carriers. Electroencephalography was collected from forty APOE genotyped older adults (Male n = 11; Mage = 79.30; Meducation = 14.88 years) during an RL task comprised of distinct phases (RL, implicit). Neural components associated with the error detection system involved in RL, the response error-related negativity (ERN) and the feedback error-related negativity (FRN), were examined for individuals at low (APOE ε4-; n=20) and high risk (APOE ε4+; n=20). RL task performance did not differ between risk groups. However, the high-risk group consistently elicited greater peak amplitudes than the low-risk group. The pattern of results indicated that the high-risk group deviated from typical RL processes such that peak amplitudes did not differ between early and late learning. Additionally, despite intact learning, latent hippocampal atrophy is believed to have disrupted the transfer and use of learned information to novel situations thus altering the hippocampal-frontostriatal circuit responsible for adaptive behavior and the corresponding neural signal. The results indicate that disease related changes can be identified prior to clinical diagnosis or functional decline using RL and a non-invasive assessment of neural function, which may prove to inform clinical conceptualization, assessment, and treatment

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

A novel method of early diagnosis of Alzheimer's disease based on EEG signals.

Studies have reported that electroencephalogram signals in Alzheimer's disease patients usually have less synchronization than those of healthy subjects. Changes in electroencephalogram signals start at early stage but, clinically, these changes are not easily detected. To detect this perturbation, three neural synchrony measurement techniques: phase synchrony, magnitude squared coherence, and cross correlation are applied to three different databases of mild Alzheimer's disease patients and healthy subjects. We have compared the right and left temporal lobes of the brain with the rest of the brain areas (frontal, central, and occipital) as temporal regions are relatively the first ones to be affected by Alzheimer's disease. Moreover, electroencephalogram signals are further classified into five different frequency bands (delta, theta, alpha beta, and gamma) because each frequency band has its own physiological significance in terms of signal evaluation. A new approach using principal component analysis before applying neural synchrony measurement techniques has been presented and compared with Average technique. The simulation results indicated that applying principal component analysis before synchrony measurement techniques shows significantly better results as compared to the lateral one. At the end, all the aforementioned techniques are assessed by a statistical test (Mann-Whitney U test) to compare the results

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep

Background: Researchers have proposed that impaired sleep may be a causal link in the progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Several recent findings suggest that enhancing deep sleep (N3) may improve neurological health in persons with MCI, and buffer the risk for AD. Specifically, Transcranial Electrical Stimulation (TES) of frontal brain areas, the inferred source of the Slow Oscillations (SOs) of N3 sleep, can extend N3 sleep duration and improve declarative memory for recently learned information. Recent work in our laboratory using dense array Electroencephalography (dEEG) localized the sources of SOs to anterior limbic sites – suggesting that targeting these sites with TES may be more effective for enhancing N3. Methods: For the present study, we recruited 13 healthy adults (M = 42 years) to participate in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic areas and a sham stimulation (placebo). We used a convolutional neural network, trained and tested on professionally scored EEG sleep staging, to predict sleep stages for each recording. Results: When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep. TES also significantly increased spectral power in the 0.5–1 Hz frequency band (relative to pre-TES epochs) in left temporoparietal and left occipital scalp regions compared to sham. Conclusion: These results suggest that even low-level TES, when specifically targeting anterior limbic sites, can increase deep (N3) sleep and thereby contribute to healthy sleep quality.Fil: Hathaway, Evan. Brain Electrophysiology Laboratory Company; Estados UnidosFil: Morgan, Kyle. Brain Electrophysiology Laboratory Company; Estados UnidosFil: Carson, Megan. Brain Electrophysiology Laboratory Company; Estados UnidosFil: Shusterman, Roma. Brain Electrophysiology Laboratory Company; Estados UnidosFil: Fernandez Corazza, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Luu, Phan. University of Oregon; Estados UnidosFil: Tucker, Don M.. University of Oregon; Estados Unido

Ensemble of classifiers based data fusion of EEG and MRI for diagnosis of neurodegenerative disorders

The prevalence of Alzheimer\u27s disease (AD), Parkinson\u27s disease (PD), and mild cognitive impairment (MCI) are rising at an alarming rate as the average age of the population increases, especially in developing nations. The efficacy of the new medical treatments critically depends on the ability to diagnose these diseases at the earliest stages. To facilitate the availability of early diagnosis in community hospitals, an accurate, inexpensive, and noninvasive diagnostic tool must be made available. As biomarkers, the event related potentials (ERP) of the electroencephalogram (EEG) - which has previously shown promise in automated diagnosis - in addition to volumetric magnetic resonance imaging (MRI), are relatively low cost and readily available tools that can be used as an automated diagnosis tool. 16-electrode EEG data were collected from 175 subjects afflicted with Alzheimer\u27s disease, Parkinson\u27s disease, mild cognitive impairment, as well as non-disease (normal control) subjects. T2 weighted MRI volumetric data were also collected from 161 of these subjects. Feature extraction methods were used to separate diagnostic information from the raw data. The EEG signals were decomposed using the discrete wavelet transform in order to isolate informative frequency bands. The MR images were processed through segmentation software to provide volumetric data of various brain regions in order to quantize potential brain tissue atrophy. Both of these data sources were utilized in a pattern recognition based classification algorithm to serve as a diagnostic tool for Alzheimer\u27s and Parkinson\u27s disease. Support vector machine and multilayer perceptron classifiers were used to create a classification algorithm trained with the EEG and MRI data. Extracted features were used to train individual classifiers, each learning a particular subset of the training data, whose decisions were combined using decision level fusion. Additionally, a severity analysis was performed to diagnose between various stages of AD as well as a cognitively normal state. The study found that EEG and MRI data hold complimentary information for the diagnosis of AD as well as PD. The use of both data types with a decision level fusion improves diagnostic accuracy over the diagnostic accuracy of each individual data source. In the case of AD only diagnosis, ERP data only provided a 78% diagnostic performance, MRI alone was 89% and ERP and MRI combined was 94%. For PD only diagnosis, ERP only performance was 67%, MRI only was 70%, and combined performance was 78%. MCI only diagnosis exhibited a similar effect with a 71% ERP performance, 82% MRI performance, and 85% combined performance. Diagnosis among three subject groups showed the same trend. For PD, AD, and normal diagnosis ERP only performance was 43%, MRI only was 66%, and combined performance was 71%. The severity analysis for mild AD, severe AD, and normal subjects showed the same combined effect