Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity.

Background: The investigation of mindfulness meditation practice, classically divided into focused attention meditation (FAM), and open monitoring meditation (OMM) styles, has seen a long tradition of theoretical, affective, neurophysiological and clinical studies. In particular, the high temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG) has been exploited to fill the gap between the personal experience of meditation practice and its neural correlates. Mounting evidence, in fact, shows that human brain activity is highly dynamic, transiting between different brain states (microstates). In this study, we aimed at exploring MEG microstates at source-level during FAM, OMM and in the resting state, as well as the complexity and criticality of dynamic transitions between microstates. Methods: Ten right-handed Theravada Buddhist monks with a meditative expertise of minimum 2,265 h participated in the experiment. MEG data were acquired during a randomized block design task (6 min FAM, 6 min OMM, with each meditative block preceded and followed by 3 min resting state). Source reconstruction was performed using eLORETA on individual cortical space, and then parcellated according to the Human Connect Project atlas. Microstate analysis was then applied to parcel level signals in order to derive microstate topographies and indices. In addition, from microstate sequences, the Hurst exponent and the Lempel-Ziv complexity (LZC) were computed. Results: Our results show that the coverage and occurrence of specific microstates are modulated either by being in a meditative state or by performing a specific meditation style. Hurst exponent values in both meditation conditions are reduced with respect to the value observed during rest, LZC shows significant differences between OMM, FAM, and REST, with a progressive increase from REST to FAM to OMM. Discussion: Importantly, we report changes in brain criticality indices during meditation and between meditation styles, in line with a state-like effect of meditation on cognitive performance. In line with previous reports, we suggest that the change in cognitive state experienced in meditation is paralleled by a shift with respect to critical points in brain dynamics.

EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Microstate Analysis Reflects Maturation of the Preterm Brain.

Preterm neonates are at risk of long-term neurodevelopmental impairments due to disruption of natural brain development. Electroencephalography (EEG) analysis can provide insights into brain development of preterm neonates. This study aims to explore the use of microstate (MS) analysis to evaluate global brain dynamics changes during maturation in preterm neonates with normal neurodevelopmental outcome.The dataset included 135 EEGs obtained from 48 neonates at varying postmenstrual ages (26.4 to 47.7 weeks), divided into four age groups. For each recording we extracted a 5-minute epoch during quiet sleep (QS) and during non-quiet sleep (NQS), resulting in eight groups (4 age group x 2 sleep states). We compared MS maps and corresponding (map-specific) MS metrics across groups using group-level maps. Additionally, we investigated individual map metrics.Four group-level MS maps accounted for approximately 70% of the global variance and showed non-random syntax. MS topographies and transitions changed significantly when neonates reached 37 weeks. For both sleep states and all MS maps, MS duration decreased and occurrence increased with age. The same relationships were found using individual maps, showing strong correlations (Pearson coefficients up to 0.74) between individual map metrics and post-menstrual age. Moreover, the Hurst exponent of the individual MS sequence decreased with age.The observed changes in MS metrics with age might reflect the development of the preterm brain, which is characterized by formation of neural networks. Therefore, MS analysis is a promising tool for monitoring preterm neonatal brain maturation, while our study can serve as a valuable reference for investigating EEGs of neonates with abnormal neurodevelopmental outcomes.

Brain dynamics of visual anticipation during spatial occlusion tasks in expert tennis players.

Stimulus identification and action outcome understanding for a rapid and accurate response selection, play a fundamental role in racquet sports. Here, we investigated the neurodynamics of visual anticipation in tennis manipulating the postural and kinematic information associated with the body of opponents by means of a spatial occlusion protocol. Event Related Potentials (ERPs) were evaluated in two groups of professional tennis players (N = 37) with different levels of expertise, while they observed pictures of opponents and predicted the landing position as fast and accurately as possible. The observed action was manipulated by deleting different body districts of the opponent (legs, ball, racket and arm, trunk). Full body image (no occlusion) was used as control condition. The worst accuracy and the slowest response time were observed in the occlusion of trunk and ball. The former was associated with a reduced amplitude of the ERP components likely linked to body processing (the N1 in the right hemisphere) and visual-motor integration awareness (the pP1), as well as with an increase of the late frontal negativity (the pN2), possibly reflecting an effort by the insula to recover and/or complete the most correct sensory-motor representation. In both occlusions, a decrease in the pP2 may reflect an impairment of decisional processes upon action execution following sensory evidence accumulation. Enhanced amplitude of the P3 and the pN2 components were found in more experienced players, suggesting a greater allocation of resources in the process connecting sensory encoding and response execution, and sensory-motor representation.

A Class-Imbalance Aware and Explainable Spatio-Temporal Graph Attention Network for Neonatal Seizure Detection.

Seizures are the most prevalent clinical indication of neurological disorders in neonates. In this study, a class-imbalance aware and explainable deep learning approach based on Convolutional Neural Networks (CNNs) and Graph Attention Networks (GATs) is proposed for the accurate automated detection of neonatal seizures. The proposed model integrates the temporal information of EEG signals with the spatial information on the EEG channels through the graph representation of the multi-channel EEG segments. One-dimensional CNNs are used to automatically develop a feature set that accurately represents the differences between seizure and nonseizure epochs in the time domain. By employing GAT, the attention mechanism is utilized to emphasize the critical channel pairs and information flow among brain regions. GAT coefficients were then used to empirically visualize the important regions during the seizure and nonseizure epochs, which can provide valuable insight into the location of seizures in the neonatal brain. Additionally, to tackle the severe class imbalance in the neonatal seizure dataset using under-sampling and focal loss techniques are used. Overall, the final Spatio-Temporal Graph Attention Network (ST-GAT) outperformed previous benchmarked methods with a mean AUC of 96.6% and Kappa of 0.88, demonstrating its high accuracy and potential for clinical applications.

Yield of EEG features as markers of disease severity in amyotrophic lateral sclerosis: a pilot study.

OBJECTIVE: To clarify the role of electroencephalography (EEG) as a promising marker of severity in amyotrophic lateral sclerosis (ALS). We characterized the brain spatio-temporal patterns activity at rest by means of both spectral band powers and EEG microstates and correlated these features with clinical scores. METHODS: Eyes closed EEG was acquired in 15 patients with ALS and spectral band power was calculated in frequency bands, defined on the basis of individual alpha frequency (IAF): delta-theta band (1-7 Hz); low alpha (IAF - 2 Hz - IAF); high alpha (IAF - IAF + 2 Hz); beta (13 - 25 Hz). EEG microstate metrics (duration, occurrence, and coverage) were also evaluated. Spectral band powers and microstate metrics were correlated with several clinical scores of disabilities and disease progression. As a control group, 15 healthy volunteers were enrolled. RESULTS: The beta-band power in motor/frontal regions was higher in patients with higher disease burden, negatively correlated with clinical severity scores and positively correlated with disease progression. Overall microstate duration was longer and microstate occurrence was lower in patients than in controls. Longer duration was correlated with a worse clinical status. CONCLUSIONS: Our results showed that beta-band power and microstate metrics may be good candidates of disease severity in ALS. Increased beta and longer microstate duration in clinically worse patients suggest a possible impairment of both motor and non-motor network activities to fast modify their status. This can be interpreted as an attempt in ALS patients to compensate the disability but resulting in an ineffective and probably maladaptive behavior.

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 - Early Breast Cancer Patients.

Oncotype Dx Recurrence Score (RS) has been validated in patients with ER + /HER2 - invasive breast carcinoma to estimate patient risk of recurrence and guide the use of adjuvant chemotherapy. We investigated the role of MRI-based radiomics features extracted from the tumor and the peritumoral tissues to predict the risk of tumor recurrence. A total of 62 patients with biopsy-proved ER + /HER2 - breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS > 25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine learning algorithm. PLS ß-weights of radiomics features included the 5% features with the largest ß-weights in magnitude (top 5%). Leave-one-out nested cross-validation (nCV) was used to achieve hyperparameter optimization and evaluate the generalizable performance of the procedure. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The exploratory analysis for the complete dataset revealed an average absolute correlation among features of 0.51. The nCV framework delivered an AUC of 0.76 (p = 1.1∙10-3). When combining "early" and "peak" DCE images of only T or TST, a tendency toward statistical significance was obtained for TST with an AUC of 0.61 (p = 0.05). The 47 features included in the top 5% were balanced between T and TST (23 and 24, respectively). Moreover, 33/47 (70%) were texture-related, and 25/47 (53%) were derived from high-resolution images (1 mm). A radiomics-based machine learning approach shows the potential to accurately predict the recurrence risk in early ER + /HER2 - breast cancer patients.

Brain electrical microstate features as biomarkers of a stable motor output.

Objective.The aim of the present study was to elucidate the brain dynamics underlying the maintenance of a constant force level exerted during a visually guided isometric contraction task by optimizing a predictive multivariate model based on global and spectral brain dynamics features.Approach.Electroencephalography (EEG) was acquired in 18 subjects who were asked to press a bulb and maintain a constant force level, indicated by a bar on a screen. For intervals of 500 ms, we calculated an index of force stability as well as indices of brain dynamics: microstate metrics (duration, occurrence, global explained variance, directional predominance) and EEG spectral amplitudes in the theta, low alpha, high alpha and beta bands. We optimized a multivariate regression model (partial least square (PLS)) where the microstate features and the spectral amplitudes were the input variables and the indexes of force stability were the output variables. The issues related to the collinearity among the input variables and to the generalizability of the model were addressed using PLS in a nested cross-validation approach.Main results.The optimized PLS regression model reached a good generalizability and succeeded to show the predictive value of microstates and spectral features in inferring the stability of the exerted force. Longer duration and higher occurrence of microstates, associated with visual and executive control networks, corresponded to better contraction performances, in agreement with the role played by the visual system and executive control network for visuo-motor integration.Significance.A combination of microstate metrics and brain rhythm amplitudes could be considered as biomarkers of a stable visually guided motor output not only at a group level, but also at an individual level. Our results may play an important role for a better understanding of the motor control in single trials or in real-time applications as well as in the study of motor control.

Levetiracetam Modulates EEG Microstates in Temporal Lobe Epilepsy.

To determine the effects of Levetiracetam (LEV) therapy using EEG microstates analysis in a population of newly diagnosed Temporal Lobe Epilepsy (TLE) patients. We hypothesized that the impact of LEV therapy on the electrical activity of the brain can be globally explored using EEG microstates. Twenty-seven patients with TLE were examined. We performed resting-state microstate EEG analysis and compared microstate metrics between the EEG performed at baseline (EEGpre) and after 3 months of LEV therapy (EEGpost). The microstates A, B, C and D emerged as the most stable. LEV induced a reduction of microstate B and D mean duration and occurrence per second (p < 0.01). Additionally, LEV treatment increased the directional predominance of microstate A to C and microstate B to D (p = 0.01). LEV treatment induces a modulation of resting-state EEG microstates in newly diagnosed TLE patients. Microstates analysis has the potential to identify a neurophysiological indicator of LEV therapeutic activity. This study of EEG microstates in people with epilepsy opens an interesting path to identify potential LEV activity biomarkers that may involve increased neuronal inhibition of the epileptic network.

A graph convolutional neural network for the automated detection of seizures in the neonatal EEG.

BACKGROUND AND OBJECTIVE: Neonatal seizures are the most common clinical presentation of neurological conditions and can have adverse effects on the neurodevelopment of the neonatal brain. Visual detection of these events from continuous EEG recordings is a laborious and time-consuming task. We propose a novel algorithm for the automated detection of neonatal seizures. METHODS: In this study, we propose a novel deep learning model based on Graph Convolutional Neural Networks for the automated detection of neonatal seizures. Unlike other methods exploiting mainly the temporal information contained in EEG signals, our method also considers long-range spatial information, i.e., the interdependencies across EEG signals. The temporal information is embedded as graph signals in the graph representation of the EEG recordings and includes EEG features extracted from the EEG signals in the time and frequency domains. The spatial information is represented as functional connections among the EEG channels (calculated by the phase-locking value and the mean squared coherence) or as maps of Euclidean distances. These different spatial representations were evaluated to assess their efficiency in providing more discriminative features for an effective detection of neonatal seizures. The model performance was assessed on a publicly available dataset of continuous EEG signals recorded from 39 neonates by means of the area under the curve (AUC) and the AUC for specificity values greater than 90% (AUC90). RESULTS: After applying post-processing, consisting in smoothing the output of the classifiers, the models based on the mean squared coherence, the phase-locking value, and the Euclidean distance respectively reached a median AUC of 99.1% (IQR: 96.8%-99.6%), 99% (IQR: 95.2%-99.7%), and 97.3% (IQR: 86.3%-99.6%), and a median AUC90 of 96%, 95.7%, and 94.9%. These values are superior or comparable to those reached by methods considered as state-of-the-art in this field. CONCLUSIONS: Our results show that the EEG graph representations drawn from functional connectivity measures can effectively leverage interdependencies among EEG signals and lead to reliable detection of neonatal seizures. Furthermore, our model has the advantage of requiring only temporal annotations on seizures for the training phase, making it more appealing for clinical applications.

Exploring brain activity for positive and negative emotions by means of EEG microstates.

Microstate analysis applied to electroencephalographic signals (EEG) allows both temporal and spatial imaging exploration and represents the activity across the scalp. Despite its potential usefulness in understanding brain activity during a specific task, it has been mostly exploited at rest. We extracted EEG microstates during the presentation of emotional expressions, presented either unilaterally (a face in one visual hemifield) or bilaterally (two faces, one in each hemifield). Results revealed four specific microstate's topographies: (i) M1 involves the temporal areas, mainly in the right hemisphere, with a higher occurrence for stimuli presented in the left than in the right visual field; (ii) M2 is localized in the left temporal cortex, with higher occurrence and coverage for unilateral than bilateral presentations; (iii) M3, with a bilateral temporo-parietal localization, shows higher coverage for bilateral than unilateral presentation; (iv) M4, mainly localized in the right fronto-parietal areas and possibly representing the hemispheric specialization for the peculiar stimulus category, shows higher occurrence and coverage for unilateral stimuli presented in the left than in the right visual field. These results suggest that microstate analysis is a valid tool to explore the cerebral response to emotions and can add new insights on the cerebral functioning, with respect to other EEG markers.

Sensory-Motor Modulations of EEG Event-Related Potentials Reflect Walking-Related Macro-Affordances.

One fundamental principle of the brain functional organization is the elaboration of sensory information for the specification of action plans that are most appropriate for interaction with the environment. Using an incidental go/no-go priming paradigm, we have previously shown a facilitation effect for the execution of a walking-related action in response to far vs. near objects/locations in the extrapersonal space, and this effect has been called "macro-affordance" to reflect the role of locomotion in the coverage of extrapersonal distance. Here, we investigated the neurophysiological underpinnings of such an effect by recording scalp electroencephalography (EEG) from 30 human participants during the same paradigm. The results of a whole-brain analysis indicated a significant modulation of the event-related potentials (ERPs) both during prime and target stimulus presentation. Specifically, consistent with a mechanism of action anticipation and automatic activation of affordances, a stronger ERP was observed in response to prime images framing the environment from a far vs. near distance, and this modulation was localized in dorso-medial motor regions. In addition, an inversion of polarity for far vs. near conditions was observed during the subsequent target period in dorso-medial parietal regions associated with spatially directed foot-related actions. These findings were interpreted within the framework of embodied models of brain functioning as arising from a mechanism of motor-anticipation and subsequent prediction error which was guided by the preferential affordance relationship between the distant large-scale environment and locomotion. More in general, our findings reveal a sensory-motor mechanism for the processing of walking-related environmental affordances.

Automated Detection and Removal of Cardiac and Pulse Interferences from Neonatal EEG Signals.

Electrical cardiac and pulsatile interference is very difficult to remove from electroencephalographic (EEG) signals, especially if recorded in neonates, for which a small number of EEG channels is used. Several methods were proposed, including Blind Source Separation (BSS) methods that required the use of artificial cardiac-related signals to improve the separation of artefactual components. To optimize the separation of cardiac-related artefactual components, we propose a method based on Independent Component Analysis (ICA) that exploits specific features of the real electrocardiographic (ECG) signals that were simultaneously recorded with the neonatal EEG. A total of forty EEG segments from 19-channel neonatal EEG recordings with and without seizures were used to test and validate the performance of our method. We observed a significant reduction in the number of independent components (ICs) containing cardiac-related interferences, with a consequent improvement in the automated classification of the separated ICs. The comparison with the expert labeling of the ICs separately containing electrical cardiac and pulsatile interference led to an accuracy = 0.99, a false omission rate = 0.01 and a sensitivity = 0.93, outperforming existing methods. Furthermore, we verified that true brain activity was preserved in neonatal EEG signals reconstructed after the removal of artefactual ICs, demonstrating the effectiveness of our method and its safe applicability in a clinical context.

Inhibition of return in time-lapse: Brain Rhythms during grip force control for spatial attention.

The inhibition of return (IoR) is the observable slowed response to a target at a cued position for cue-target intervals of longer than 300 ms; when there has been enough time to disengage from a previously-cued location, an inhibitory after-effect can be observed. Studies aimed at understanding whether mechanisms underlying IoR act at a perceptual/attentional or a later response-execution stage have offered divergent results. Though focusing on the brain's responses to cue-target intervals can offer significant information on the nature of IoR, few studies have investigated neural activity during this interval; these studies suggest the generation of inhibitory tags on the spatial coordinates of the previously attended position which, in turn, inhibit motor programming toward that position. As such, a cue-target task was administered in this study; the rhythmic activity of EEG signals on the entire cue-target interval was measured to determine whether IoR is referred to early or late response processing stages. A visually-guided force variation during isometric contraction, instead of a key press response, was required to reduce the effect of motor response initiation. Our results indicated the prominent involvement of the fronto-parietal and occipital cortical areas post-cue appearance, with a peculiar theta band modulation characterizing the posterior parietal cortex. Theta activity in this region was enhanced post-cue onset, decreased over time, and was enhanced again when a target appeared in an unexpected location rather than in a cued position. This suggests that the mechanism that generates IoR sequentially affects perceptual/attentional processing and motor preparation rather than response execution.

Machine learning for predicting levetiracetam treatment response in temporal lobe epilepsy.

OBJECTIVE: To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach. METHODS: Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome. RESULTS: A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained. CONCLUSIONS: This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy. SIGNIFICANCE: Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.

Radiomics-based machine learning differentiates "ground-glass" opacities due to COVID-19 from acute non-COVID-19 lung disease.

Ground-glass opacities (GGOs) are a non-specific high-resolution computed tomography (HRCT) finding tipically observed in early Coronavirus disesase 19 (COVID-19) pneumonia. However, GGOs are also seen in other acute lung diseases, thus making challenging the differential diagnosis. To this aim, we investigated the performance of a radiomics-based machine learning method to discriminate GGOs due to COVID-19 from those due to other acute lung diseases. Two sets of patients were included: a first set of 28 patients (COVID) diagnosed with COVID-19 infection confirmed by real-time polymerase chain reaction (RT-PCR) between March and April 2020 having (a) baseline HRCT at hospital admission and (b) predominant GGOs pattern on HRCT; a second set of 30 patients (nCOVID) showing (a) predominant GGOs pattern on HRCT performed between August 2019 and April 2020 and (b) availability of final diagnosis. Two readers independently segmented GGOs on HRCTs using a semi-automated approach, and radiomics features were extracted using a standard open source software (PyRadiomics). Partial least square (PLS) regression was used as the multivariate machine-learning algorithm. A leave-one-out nested cross-validation was implemented. PLS ß-weights of radiomics features, including the 5% features with the largest ß-weights in magnitude (top 5%), were obtained. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. The Youden's test assessed sensitivity and specificity of the classification. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The predictive model delivered an AUC of 0.868 (Youden's index = 0.68, sensitivity = 93%, specificity 75%, p = 4.2 × 10-7). Of the seven features included in the top 5% features, five were texture-related. A radiomics-based machine learning signature showed the potential to accurately differentiate GGOs due to COVID-19 pneumonia from those due to other acute lung diseases. Most of the discriminant radiomics features were texture-related. This approach may assist clinician to adopt the appropriate management early, while improving the triage of patients.

Characterization of the Functional Dynamics in the Neonatal Brain during REM and NREM Sleep States by means of Microstate Analysis.

Neonates spend most of their life sleeping. During sleep, their brain experiences fast changes in its functional organization. Microstate analysis permits to capture the rapid dynamical changes occurring in the functional organization of the brain by representing the changing spatio-temporal features of the electroencephalogram (EEG) as a sequence of short-lasting scalp topographies-the microstates. In this study, we modeled the ongoing neonatal EEG into sequences of a limited number of microstates and investigated whether the extracted microstate features are altered in REM and NREM sleep (usually known as active and quiet sleep states-AS and QS-in the newborn) and depend on the EEG frequency band. 19-channel EEG recordings from 60 full-term healthy infants were analyzed using a modified version of the k-means clustering algorithm. The results show that ~ 70% of the variance in the datasets can be described using 7 dominant microstate templates. The mean duration and mean occurrence of the dominant microstates were significantly different in the two sleep states. Microstate syntax analysis demonstrated that the microstate sequences characterizing AS and QS had specific non-casual structures that differed in the two sleep states. Microstate analysis of the neonatal EEG in specific frequency bands showed a clear dependence of the explained variance on frequency. Overall, our findings demonstrate that (1) the spatio-temporal dynamics of the neonatal EEG can be described by non-casual sequences of a limited number of microstate templates; (2) the brain dynamics described by these microstate templates depends on frequency; (3) the features of the microstate sequences can well differentiate the physiological conditions characterizing AS and QS.

Evidence of Neurovascular Un-Coupling in Mild Alzheimer's Disease through Multimodal EEG-fNIRS and Multivariate Analysis of Resting-State Data.

Alzheimer's disease (AD) is associated with modifications in cerebral blood perfusion and autoregulation. Hence, neurovascular coupling (NC) alteration could become a biomarker of the disease. NC might be assessed in clinical settings through multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Multimodal EEG-fNIRS was recorded at rest in an ambulatory setting to assess NC and to evaluate the sensitivity and specificity of the methodology to AD. Global NC was evaluated with a general linear model (GLM) framework by regressing whole-head EEG power envelopes in three frequency bands (theta, alpha and beta) with average fNIRS oxy- and deoxy-hemoglobin concentration changes in the frontal and prefrontal cortices. NC was lower in AD compared to healthy controls (HC) with significant differences in the linkage of theta and alpha bands with oxy- and deoxy-hemoglobin, respectively (p = 0.028 and p = 0.020). Importantly, standalone EEG and fNIRS metrics did not highlight differences between AD and HC. Furthermore, a multivariate data-driven analysis of NC between the three frequency bands and the two hemoglobin species delivered a cross-validated classification performance of AD and HC with an Area Under the Curve, AUC = 0.905 (p = 2.17 × 10-5). The findings demonstrate that EEG-fNIRS may indeed represent a powerful ecological tool for clinical evaluation of NC and early identification of AD.