Impact of maternal depressive symptoms on offspring executive functions: a systematic review.

OBJECTIVE: This systematic review aims to thoroughly examine the current understanding of the effect of maternal depression exposure on the executive functions of offspring. METHODS: Following the PRISMA statement, a comprehensive search for peer-reviewed cohort studies was performed on Pubmed, ScienceDirect, LILACS, PsychINFO, and SciELO. Study quality was assessed using the NIH National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-sectional studies. The evidence was evaluated using the Grading of Recommendation, Assessment, Development, and Evaluation. RESULTS: This review analyzed 33 cohort studies from different countries with a total of 38,981 participants. Twenty-four studies confirmed the hypothesis of the harmful effect of maternal depressive symptoms on the performance of children's executive functions. However, a high heterogeneity among studies was found, and meta-analysis was not feasible. Fetal programming, genetics, and parental practices have been identified as potential mechanisms that can affect the executive functions of children born to mothers who have experienced depressive symptoms. CONCLUSIONS: The results suggest a negative association between maternal depressive symptoms and offspring executive functioning. Further studies on the effects of chronicity/severity of maternal symptoms and changes in executive functions in different sensitive periods are needed.

Specific Patterns of Endogenous Functional Connectivity Are Associated With Harm Avoidance in Obsessive-Compulsive Disorder.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance. We hypothesized that 1) HA, not an OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2) HA-specific findings would be robust to comorbid symptoms; and 3) reliable findings would replicate in a holdout testing subsample. METHODS: Using resting-state functional connectivity magnetic resonance imaging, cross-validated elastic net for feature selection, and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample (n = 73; 71.8% female; healthy control group n = 36, OCD group n = 37); robustness to comorbidities; and replicability in a testing subsample (n = 30; 56.7% female; healthy control group n = 15, OCD group n = 15). RESULTS: Stronger inverse connectivity between the right dorsal anterior cingulate cortex and right basolateral amygdala and stronger positive connectivity between the right ventral anterior insula and left ventral striatum were associated with greater HA across groups. Network connections did not discriminate OCD diagnostic status or predict HA-correlated traits, suggesting sensitivity to trait HA. The dorsal anterior cingulate cortex-basolateral amygdala relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. CONCLUSIONS: Stronger inverse dorsal anterior cingulate cortex-basolateral amygdala connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent avoidance-related network to OCD, with implications for precision-based approaches and treatment.

Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex.

Three large-scale networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VANet and DANet) and salience (SNet) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VANet and DANet, but there is a gap in the current knowledge regarding its involvement in the SNet. Herein, we used a translational and multimodal approach to demonstrate the existence of a SNet node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomical connectivity strength between different vlPFC areas and the frontal and insular cortices. The strongest connections were with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) - the main cortical SNet nodes. These inputs converged in the caudal area 47/12, an area that has strong projections to subcortical structures associated with the SNet. Second, we used resting-state functional MRI (rsfMRI) in NHP data to validate this SNet node. Third, we used rsfMRI in the human to identify a homologous caudal 47/12 region that also showed strong connections with the SNet cortical nodes. Taken together, these data confirm a SNet node in the vlPFC, demonstrating that the vlPFC contains nodes for all three cognitive networks: VANet, DANet, and SNet. Thus, the vlPFC is in a position to switch between these three networks, pointing to its key role as an attentional hub. Its additional connections to the orbitofrontal, dorsolateral, and premotor cortices, place the vlPFC at the center for switching behaviors based on environmental stimuli, computing value, and cognitive control.

Multimodal resting-state connectivity predicts affective neurofeedback performance.

Neurofeedback has been suggested as a potential complementary therapy to different psychiatric disorders. Of interest for this approach is the prediction of individual performance and outcomes. In this study, we applied functional connectivity-based modeling using electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) modalities to (i) investigate whether resting-state connectivity predicts performance during an affective neurofeedback task and (ii) evaluate the extent to which predictive connectivity profiles are correlated across EEG and fNIRS techniques. The fNIRS oxyhemoglobin and deoxyhemoglobin concentrations and the EEG beta and gamma bands modulated by the alpha frequency band (beta-m-alpha and gamma-m-alpha, respectively) recorded over the frontal cortex of healthy subjects were used to estimate functional connectivity from each neuroimaging modality. For each connectivity matrix, relevant edges were selected in a leave-one-subject-out procedure, summed into "connectivity summary scores" (CSS), and submitted as inputs to a support vector regressor (SVR). Then, the performance of the left-out-subject was predicted using the trained SVR model. Linear relationships between the CSS across both modalities were evaluated using Pearson's correlation. The predictive model showed a mean absolute error smaller than 20%, and the fNIRS oxyhemoglobin CSS was significantly correlated with the EEG gamma-m-alpha CSS (r = -0.456, p = 0.030). These results support that pre-task electrophysiological and hemodynamic resting-state connectivity are potential predictors of neurofeedback performance and are meaningfully coupled. This investigation motivates the use of joint EEG-fNIRS connectivity as outcome predictors, as well as a tool for functional connectivity coupling investigation.

Affective Neurofeedback Under Naturalistic Conditions: A Mini-Review of Current Achievements and Open Challenges.

Affective neurofeedback training allows for the self-regulation of the putative circuits of emotion regulation. This approach has recently been studied as a possible additional treatment for psychiatric disorders, presenting positive effects in symptoms and behaviors. After neurofeedback training, a critical aspect is the transference of the learned self-regulation strategies to outside the laboratory and how to continue reinforcing these strategies in non-controlled environments. In this mini-review, we discuss the current achievements of affective neurofeedback under naturalistic setups. For this, we first provide a brief overview of the state-of-the-art for affective neurofeedback protocols. We then discuss virtual reality as a transitional step toward the final goal of "in-the-wild" protocols and current advances using mobile neurotechnology. Finally, we provide a discussion of open challenges for affective neurofeedback protocols in-the-wild, including topics such as convenience and reliability, environmental effects in attention and workload, among others.

Subject-independent decoding of affective states using functional near-infrared spectroscopy.

Affective decoding is the inference of human emotional states using brain signal measurements. This approach is crucial to develop new therapeutic approaches for psychiatric rehabilitation, such as affective neurofeedback protocols. To reduce the training duration and optimize the clinical outputs, an ideal clinical neurofeedback could be trained using data from an independent group of volunteers before being used by new patients. Here, we investigated if this subject-independent design of affective decoding can be achieved using functional near-infrared spectroscopy (fNIRS) signals from frontal and occipital areas. For this purpose, a linear discriminant analysis classifier was first trained in a dataset (49 participants, 24.65±3.23 years) and then tested in a completely independent one (20 participants, 24.00±3.92 years). Significant balanced accuracies between classes were found for positive vs. negative (64.50 ± 12.03%, p<0.01) and negative vs. neutral (68.25 ± 12.97%, p<0.01) affective states discrimination during a reactive block consisting in viewing affective-loaded images. For an active block, in which volunteers were instructed to recollect personal affective experiences, significant accuracy was found for positive vs. neutral affect classification (71.25 ± 18.02%, p<0.01). In this last case, only three fNIRS channels were enough to discriminate between neutral and positive affective states. Although more research is needed, for example focusing on better combinations of features and classifiers, our results highlight fNIRS as a possible technique for subject-independent affective decoding, reaching significant classification accuracies of emotional states using only a few but biologically relevant features.

A prefrontal network integrates preferences for advance information about uncertain rewards and punishments.

Humans and animals can be strongly motivated to seek information to resolve uncertainty about rewards and punishments. In particular, despite its clinical and societal relevance, very little is known about information seeking about punishments. We show that attitudes toward information about punishments and rewards are distinct and separable at both behavioral and neuronal levels. We demonstrate the existence of prefrontal neuronal populations that anticipate opportunities to gain information in a relatively valence-specific manner, separately anticipating information about either punishments or rewards. These neurons are located in anatomically interconnected subregions of anterior cingulate cortex (ACC) and ventrolateral prefrontal cortex (vlPFC) in area 12o/47. Unlike ACC, vlPFC also contains a population of neurons that integrate attitudes toward both reward and punishment information, to encode the overall preference for information in a bivalent manner. This cortical network is well suited to mediate information seeking by integrating the desire to resolve uncertainty about multiple, distinct motivational outcomes.

Closed-loop neurostimulation for affective symptoms and disorders: An overview.

Affective and anxiety disorders are the most prevalent and incident psychiatric disorders worldwide. Therapeutic approaches to these disorders using non-invasive brain stimulation (NIBS) and analogous techniques have been extensively investigated. In this paper, we discuss the combination of NIBS and neurofeedback in closed-loop setups and its application for affective symptoms and disorders. For this, we first provide a rationale for this combination by presenting some of the main original findings of NIBS, with a primary focus on transcranial magnetic stimulation (TMS), and neurofeedback, including protocols based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Then, we provide a scope review of studies combining real-time neurofeedback with NIBS protocols in the so-called closed-loop brain state-dependent neuromodulation (BSDS). Finally, we discuss the concomitant use of TMS and real-time functional near-infrared spectroscopy (fNIRS) as a possible solution to the current limitations of BSDS-based protocols for affective and anxiety disorders.

Neurofeedback and the Aging Brain: A Systematic Review of Training Protocols for Dementia and Mild Cognitive Impairment.

Dementia describes a set of symptoms that occur in neurodegenerative disorders and that is characterized by gradual loss of cognitive and behavioral functions. Recently, non-invasive neurofeedback training has been explored as a potential complementary treatment for patients suffering from dementia or mild cognitive impairment. Here we systematically reviewed studies that explored neurofeedback training protocols based on electroencephalography or functional magnetic resonance imaging for these groups of patients. From a total of 1,912 screened studies, 10 were included in our final sample (N = 208 independent participants in experimental and N = 81 in the control groups completing the primary endpoint). We compared the clinical efficacy across studies, and evaluated their experimental designs and reporting quality. In most studies, patients showed improved scores in different cognitive tests. However, data from randomized controlled trials remains scarce, and clinical evidence based on standardized metrics is still inconclusive. In light of recent meta-research developments in the neurofeedback field and beyond, quality and reporting practices of individual studies are reviewed. We conclude with recommendations on best practices for future studies that investigate the effects of neurofeedback training in dementia and cognitive impairment.

Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices.

Major depressive disorder (MDD) is the leading cause of disability worldwide. Neurofeedback training has been suggested as a potential additional treatment option for MDD patients not reaching remission from standard care (i.e., psychopharmacology and psychotherapy). Here we systematically reviewed neurofeedback studies employing electroencephalography, or functional magnetic resonance-based protocols in depressive patients. Of 585 initially screened studies, 24 were included in our final sample (N = 480 patients in experimental and N = 194 in the control groups completing the primary endpoint). We evaluated the clinical efficacy across studies and attempted to group studies according to the control condition categories currently used in the field that affect clinical outcomes in group comparisons. In most studies, MDD patients showed symptom improvement superior to the control group(s). However, most articles did not comply with the most stringent study quality and reporting practices. We conclude with recommendations on best practices for experimental designs and reporting standards for neurofeedback training.

EEG spectro-temporal amplitude modulation as a measurement of cortical hemodynamics: an EEG-fNIRS study.

Neurovascular coupling provides valuable descriptive information about neural function and communication. In this work, we propose to objectively characterize EEG sub-band modulation in an attempt to compare with local variations of fNIRS hemoglobin concentration. First, full-band EEG signals are decomposed into five well-known frequency sub-bands: delta, theta, alpha, beta, and gamma. The temporal amplitude envelope of each sub-band is then computed via Hilbert transformation. The proposed EEG 'spectro-temporal amplitude modulation' (EEG-AM) feature measures the rate at which each sub-band is modulated. Similarities between EEG-AM features and fNIRS hemoglobin concentration are computed for four neighboring channels over the occipital area during resting-state. Experiments with a database of 29 participants show statistically significant similarities between the total hemoglobin concentration and the alpha band modulating the alpha, beta, and gamma frequencies. These results support the idea that the EEG-AM can carry hemodynamic properties.Clinical relevance- This shows that the EEG spectro-temporal amplitude modulation present similarities with the hemoglobin concentration in co-placed channels.

Resting-state global EEG connectivity predicts depression and anxiety severity.

There is a recent interest in finding neurophysiological biomarkers which will facilitate the diagnosis and understanding of the neural basis of different psychiatric disorders. In this paper, we evaluated the resting-state global EEG connectivity as a potential biomarker for depressive and anxiety symptoms. For this, we evaluated a population of 119 subjects, including 75 healthy subjects and 44 patients with major depressive disorder. We calculated the global connectivity (spectral coherence) in a setup of 60 EEG channels, for six different spectral bands: theta, alpha1, alpha2, beta1, beta2, and gamma. These global connectivity scores were used to train a Support Vector Regressor to predict symptoms measured by the Beck Depression Inventory (BDI) and the Spielberger Trait Anxiety Inventory (TAI). Experiments showed a significant prediction of both symptoms, with a mean absolute error (MAE) of 8.07±6.98 and 11.52±8.7 points, respectively. Among the most discriminating features, the global connectivity in the alpha2 band (10.0-12.0Hz) presented significantly positive Spearman's correlation with the depressive (rho = 0.32, pFDR <0.01), and the anxiety symptoms (rho = 0.26, pFDR<0.01).Clinical relevance-This study demonstrates that EEG global connectivity can be used to predict depression and anxiety symptoms measured by widely used questionnaires.

Predicting affective valence using cortical hemodynamic signals.

Ascribing affective valence to stimuli or mental states is a fundamental property of human experiences. Recent neuroimaging meta-analyses favor the workspace hypothesis for the neural underpinning of valence, in which both positive and negative values are encoded by overlapping networks but are associated with different patterns of activity. In the present study, we further explored this framework using functional near-infrared spectroscopy (fNIRS) in conjunction with multivariate analyses. We monitored the fronto-temporal and occipital hemodynamic activity of 49 participants during the viewing of affective images (passive condition) and during the imagination of affectively loaded states (active condition). Multivariate decoding techniques were applied to determine whether affective valence is encoded in the cortical areas assessed. Prediction accuracies of 89.90 ± 13.84% and 85.41 ± 14.43% were observed for positive versus neutral comparisons, and of 91.53 ± 13.04% and 81.54 ± 16.05% for negative versus neutral comparisons (passive/active conditions, respectively). Our results are consistent with previous studies using other neuroimaging modalities that support the affective workspace hypothesis and the notion that valence is instantiated by the same network, regardless of whether the affective experience is passively or actively elicited.

Functional near-infrared spectroscopy-based affective neurofeedback: feedback effect, illiteracy phenomena, and whole-connectivity profiles.

Background: Affective neurofeedback constitutes a suitable approach to control abnormal neural activities associated with psychiatric disorders and might consequently relief symptom severity. However, different aspects of neurofeedback remain unclear, such as its neural basis, the performance variation, the feedback effect, among others. Aim: First, we aimed to propose a functional near-infrared spectroscopy (fNIRS)-based affective neurofeedback based on the self-regulation of frontal and occipital networks. Second, we evaluated three different feedback approaches on performance: real, fixed, and random feedback. Third, we investigated different demographic, psychological, and physiological predictors of performance. Approach: Thirty-three healthy participants performed a task whereby an amorphous figure changed its shape according to the elicited affect (positive or neutral). During the task, the participants randomly received three different feedback approaches: real feedback, with no change of the classifier output; fixed feedback, keeping the feedback figure unmodified; and random feedback, where the classifier output was multiplied by an arbitrary value, causing a feedback different than expected by the subject. Then, we applied a multivariate comparison of the whole-connectivity profiles according to the affective states and feedback approaches, as well as during a pretask resting-state block, to predict performance. Results: Participants were able to control this feedback system with 70.00 % ± 24.43 % ( p < 0.01 ) of performance during the real feedback trials. No significant differences were found when comparing the average performances of the feedback approaches. However, the whole functional connectivity profiles presented significant Mahalanobis distances ( p ≪ 0.001 ) when comparing both affective states and all feedback approaches. Finally, task performance was positively correlated to the pretask resting-state whole functional connectivity ( r = 0.512 , p = 0.009 ). Conclusions: Our results suggest that fNIRS might be a feasible tool to develop a neurofeedback system based on the self-regulation of affective networks. This finding enables future investigations using an fNIRS-based affective neurofeedback in psychiatric populations. Furthermore, functional connectivity profiles proved to be a good predictor of performance and suggested an increased effort to maintain task control in the presence of feedback distractors.

Impact of communicative head movements on the quality of functional near-infrared spectroscopy signals: negligible effects for affirmative and negative gestures and consistent artifacts related to raising eyebrows.

Functional near-infrared spectroscopy (fNIRS) is currently one of the most promising tools in the neuroscientific research to study brain hemodynamics during naturalistic social communication. The application of fNIRS by studies in this field of knowledge has been widely justified by its strong resilience to motion artifacts, including those that might be generated by communicative head and facial movements. Previous studies have focused on the identification and correction of these artifacts, but a quantification of the differential contribution of common communicative movements on the quality of fNIRS signals is still missing. We assessed the impact of four movements (nodding head up and down, reading aloud, nodding head sideways, and raising eyebrows) performed during rest and task conditions on two metrics of signal quality control: an estimative of signal-to-noise performance and the negative correlation between oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb). Channel-wise group analysis confirmed the robustness of the fNIRS technique to head nodding movements but showed a large effect of raising eyebrows in both signal quality control metrics, both during task and rest conditions. Reading aloud did not disrupt the expected anticorrelation between oxy-Hb and deoxy-Hb but had a relatively large effect on signal-to-noise performance. These findings may have implications to the interpretation of fNIRS studies examining communicative processes.

The relevance of feature selection methods to the classification of obsessive-compulsive disorder based on volumetric measures.

BACKGROUND: Magnetic resonance images (MRI) show detectable anatomical and functional differences between individuals with obsessive-compulsive disorder (OCD) and healthy subjects. Moreover, machine learning techniques have been proposed as tools to identify potential biomarkers and, ultimately, to support clinical diagnosis. However, few studies to date have investigated feature selection (FS) influences in OCD MRI-based classification. METHODS: Volumes of cortical and subcortical structures, from MRI data of 38 OCD patients (split into two groups according symptoms severity) and 36 controls, were submitted to seven feature selection algorithms. FS aims to select the most relevant and less redundant features which discriminate between two classes. Then, a classification step was applied, from which the classification performances before and after different FS were compared. For the performance evaluation, leave-one-subject-out accuracies of Support Vector Machine classifiers were considered. RESULTS: Using different FS algorithms, performance improvement was achieved for Controls vs. All OCD discrimination (19.08% of improvement reducing by 80% the amount of features), Controls vs. Low OCD (20.10%, 75%), Controls vs. High OCD (17.32%, 85%) and Low OCD vs. High OCD (10.53%, 75%). Furthermore, all algorithms pointed out classical cortico-striato-thalamo-cortical circuitry structures as relevant features for OCD classification. LIMITATIONS: Limitations include the sample size and using only filter approaches for FS. CONCLUSIONS: Our results suggest that FS positively impacts OCD classification using machine-learning techniques. Complementarily, FS algorithms were able to select biologically plausible features automatically.

Imaging Brain Function with Functional Near-Infrared Spectroscopy in Unconstrained Environments.

Assessing the neural correlates of motor and cognitive processes under naturalistic experimentation is challenging due to the movement constraints of traditional brain imaging technologies. The recent advent of portable technologies that are less sensitive to motion artifacts such as Functional Near Infrared Spectroscopy (fNIRS) have been made possible the study of brain function in freely-moving participants. In this paper, we describe a series of proof-of-concept experiments examining the potential of fNIRS in assessing the neural correlates of cognitive and motor processes in unconstrained environments. We show illustrative applications for practicing a sport (i.e., table tennis), playing a musical instrument (i.e., piano and violin) alone or in duo and performing daily activities for many hours (i.e., continuous monitoring). Our results expand upon previous research on the feasibility and robustness of fNIRS to monitor brain hemodynamic changes in different real life settings. We believe that these preliminary results showing the flexibility and robustness of fNIRS measurements may contribute by inspiring future work in the field of applied neuroscience.

Clinician's road map to wavelet EEG as an Alzheimer's disease biomarker.

Alzheimer's disease (AD) is considered the main cause of dementia in Western countries. Consequently, there is a need for an accurate, universal, specific and cost-effective biomarker for early AD diagnosis, to follow disease progression and therapy response. This article describes a new diagnostic approach to quantitative electroencephalogram (QEEG) diagnosis of mild and moderate AD. The data set used in this study was composed of EEG signals recorded from 2 groups: (S1) 74 normal subjects, 33 females and 41 males (mean age 67 years, standard deviation = 8) and (S2) 88 probable AD patients (NINCDS-ADRDA criteria), 55 females and 33 males (mean age 74.7 years, standard deviation = 7.8) with mild to moderate symptoms (DSM-IV-TR). Attention is given to sample size and the use of state of the art open source tools (LetsWave and WEKA) to process the EEG data. This innovative technique consists in associating Morlet wavelet filter with a support vector machine technique. A total of 111 EEG features (attributes) were obtained for 162 probands. The results were accuracy of 92.72% and area under the curve of 0.92 (percentage split test). Most important, comparing a single patient versus the total data set resulted in accuracy of 84.56% (leave-one-patient-out test). Particular emphasis was on clinical diagnosis and feasibility of implementation of this low-cost procedure, because programming knowledge is not required. Consequently, this new method can be useful to support AD diagnosis in resource-limited settings.

Improving Alzheimer's disease diagnosis with machine learning techniques.

There is not a specific test to diagnose Alzheimer's disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity.

EEG spectro-temporal modulation energy: a new feature for automated diagnosis of Alzheimer's disease.

There is recent indication that Alzheimer's disease (AD) can be characterized by atypical modulation of electrophysiological brain activity caused by fibrillar amyloid deposition in specific regions of the brain, such as those related to cognition and memory. In this paper, we propose to objectively characterize EEG sub-band modulation in an attempt to develop an automated noninvasive AD diagnostics tool. First, multi-channel full-band EEG signals are decomposed into five well-known frequency sub-bands: delta, theta, alpha, beta, and gamma. The temporal amplitude envelope of each sub-band is then computed via a Hilbert transformation. The proposed 'spectro-temporal modulation energy' feature measures the rate with which each sub-band is modulated. Modulation energy features are computed for 19 referential EEG signals and seven bipolar signals. Salient features are then selected and used to train four different classifiers, namely, support vector machines, logistic regression, classification and regression trees, and neural networks. Experiments with a database of 34 participants, 22 of which have been clinically diagnosed with probable-AD, show a neural network classifier achieving over 91% accuracy, thus significantly outperforming a classifier trained with conventional spectral-based features.