Exploring the disruptions of the neurophysiological organization in Alzheimer's disease: An integrative approach.

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is a neurological disorder that impairs brain functions associated with cognition, memory, and behavior. Noninvasive neurophysiological techniques like magnetoencephalography (MEG) and electroencephalography (EEG) have shown promise in reflecting brain changes related to AD. These techniques are usually assessed at two levels: local activation (spectral, nonlinear, and dynamic properties) and global synchronization (functional connectivity, frequency-dependent network, and multiplex network organization characteristics). Nonetheless, the understanding of the organization formed by the existing relationships between these levels, henceforth named neurophysiological organization, remains unexplored. This work aims to assess the alterations AD causes in the resting-state neurophysiological organization. METHODS: To that end, three datasets from healthy controls (HC) and patients with dementia due to AD were considered: MEG database (55 HC and 87 patients with AD), EEG1 database (51 HC and 100 patients with AD), and EEG2 database (45 HC and 82 patients with AD). To explore the alterations induced by AD in the relationships between several features extracted from M/EEG data, association networks (ANs) were computed. ANs are graphs, useful to quantify and visualize the intricate relationships between multiple features. RESULTS: Our results suggested a disruption in the neurophysiological organization of patients with AD, exhibiting a greater inclination towards the local activation level; and a significant decrease in the complexity and diversity of the ANs (p-value ¡ 0.05, Mann-Whitney U-test, Bonferroni correction). This effect might be due to a shift of the neurophysiological organization towards more regular configurations, which may increase its vulnerability. Moreover, our findings support the crucial role played by the local activation level in maintaining the stability of the neurophysiological organization. Classification performance exhibited accuracy values of 83.91%, 73.68%, and 72.65% for MEG, EEG1, and EEG2 databases, respectively. CONCLUSION: This study introduces a novel, valuable methodology able to integrate parameters characterize different properties of the brain activity and to explore the intricate organization of the neurophysiological organization at different levels. It was noted that AD increases susceptibility to changes in functional neural organization, suggesting a greater ease in the development of severe impairments. Therefore, ANs could facilitate a deeper comprehension of the complex interactions in brain function from a global standpoint.

Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Functional network properties in schizophrenia and bipolar disorder assessed with high-density electroencephalography.

BACKGROUND: The study of the cortical functional network properties in schizophrenia (SZ) may benefit from the use of graph theory parameters applied to high-density electroencephalography (EEG). Connectivity Strength (CS) assesses global synchrony of the network, and Shannon Graph Complexity (SGC) summarizes the network distribution of link weights and allows distinguishing between primary and secondary pathways. Their joint use may help in understanding the underpinnings of the functional network hyperactivation and task-related hypomodulation previously described in psychoses. METHODS: We used 64-sensor EEG recordings during a P300 oddball task in 128 SZ patients (96 chronic, CR, and 32 first episodes, FE), as well as 46 bipolar disorder (BD) patients, and 92 healthy controls (HC). Pre-stimulus and modulation (task-response minus pre-stimulus windows values) of CS and SGC were assessed in the theta band (4-8 Hz) and the broadband (4-70 Hz). RESULTS: Compared to HC, SZ patients (CR and FE) showed significantly higher pre-stimulus CS values in the broadband, and both SZ and BD patients showed lower theta-band CS modulation. SGC modulation values, both theta-band and broadband, were also abnormally reduced in CR patients. Statistically significant relationships were found in the theta band between SGC modulation and both CS pre-stimulus and modulation values in patients. CS altered measures in patients were additionally related to their cognitive outcome and negative symptoms. A primary role of antipsychotics in these results was ruled out. CONCLUSIONS: Our results linking SGC and CS alterations in psychotic patients supported a hyperactive and hypomodulatory network mainly involving connections in secondary pathways.

Connectivity-based Meta-Bands: A new approach for automatic frequency band identification in connectivity analyses.

The majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as "canonical" frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the "Connectivity-based Meta-Bands" (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation are partially aligned with the underlying network topologies at group level for the MEG signals, but they are missing individual idiosyncrasies that may be biasing previous studies, as revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited, revealing a simpler frequency parcellation, not aligned with that defined by the "canonical" frequency bands. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.

Electrical analysis of logical complexity: an exploratory eeg study of logically valid/invalid deducive inference.

INTRODUCTION: Logically valid deductive arguments are clear examples of abstract recursive computational procedures on propositions or on probabilities. However, it is not known if the cortical time-consuming inferential processes in which logical arguments are eventually realized in the brain are in fact physically different from other kinds of inferential processes. METHODS: In order to determine whether an electrical EEG discernible pattern of logical deduction exists or not, a new experimental paradigm is proposed contrasting logically valid and invalid inferences with exactly the same content (same premises and same relational variables) and distinct logical complexity (propositional truth-functional operators). Electroencephalographic signals from 19 subjects (24.2 ± 3.3 years) were acquired in a two-condition paradigm (100 trials for each condition). After the initial general analysis, a trial-by-trial approach in beta-2 band allowed to uncover not only evoked but also phase asynchronous activity between trials. RESULTS: showed that (i) deductive inferences with the same content evoked the same response pattern in logically valid and invalid conditions, (ii) mean response time in logically valid inferences is 61.54% higher, (iii) logically valid inferences are subjected to an early (400 ms) and a late reprocessing (600 ms) verified by two distinct beta-2 activations (p-value < 0,01, Wilcoxon signed rank test). CONCLUSION: We found evidence of a subtle but measurable electrical trait of logical validity. Results put forward the hypothesis that some logically valid deductions are recursive or computational cortical events.

Quantification of the robustness of functional neural networks: application to the characterization of Alzheimer's disease continuum.

Objective.Brain connectivity networks are usually characterized in terms of properties coming from the complex network theory. Using new measures to summarize the attributes of functional connectivity networks can be an important step for their better understanding and characterization, as well as to comprehend the alterations associated with neuropsychiatric and neurodegenerative disorders. In this context, the main objective of this study was to introduce a novel methodology to evaluate network robustness, which was subsequently applied to characterize the brain activity in the Alzheimer's disease (AD) continuum.Approach.Functional connectivity networks were built using 478 electroencephalographic and magnetoencephalographic resting-state recordings from three different databases. These functional connectivity networks computed in the conventional frequency bands were modified simulating an iterative attack procedure using six different strategies. The network changes caused by these attacks were evaluated by means of Spearman's correlation. The obtained results at the conventional frequency bands were aggregated in a correlation surface, which was characterized in terms of four gradient distribution properties: mean, variance, skewness, and kurtosis.Main results.The new proposed methodology was able to consistently quantify network robustness. Our results showed statistically significant differences in the inherent ability of the network to deal with attacks (i.e. differences in network robustness) between controls, mild cognitive impairment subjects, and AD patients for the three different databases. In addition, we found a significant correlation between mini-mental state examination scores and the changes in network robustness.Significance.To the best of our knowledge, this is the first study which assesses the robustness of the functional connectivity network in the AD continuum. Our findings consistently evidence the loss of network robustness as the AD progresses for the three databases. Furthermore, the changes in this complex network property may be related with the progressive deterioration in brain functioning due to AD.

Slow EEG Oscillation to Characterize Pediatric Sleep Apnea and Associated Cognitive Impairments.

Previous studies have suggested that the typical slow oscillations (SO) characteristics during sleep could be modified in the presence of pediatric obstructive sleep apnea (OSA). Here, we evaluate whether these modifications are significant and if they may reflect cognitive deficits. We recorded the overnight electroencephalogram (EEG) of 294 pediatric subjects (5-9 years old) using eight channels. Then, we divided the cohort in three OSA severity groups (no OSA, mild, and moderate/severe) to characterize the corresponding SO using the spectral maximum in the slow wave sleep (SWS) band δ1: 0.1-2 Hz (Maxs o), as well as the frequency where this maximum is located (FreqMaxso). Spectral entropy (SpecEn) from δ1 was also included in the analyses. A correlation analysis was performed to evaluate associations of these spectral measures with six OSA-related clinical variables and six cognitive scores. Our results indicate that Maxso could be used as a moderate/severe OSA biomarker while providing useful information regarding verbal and visuo-spatial impairments, and that FreqMaxso emerges as an even more robust indicator of visuospatial function. In addition, we uncovered novel insights regarding the ability of SpecEn in δ1 to characterize OSA-related disruption of sleep homeostasis. Our findings suggest that the information from SO may be useful to automatically characterize moderate/severe pediatric OSA and its cognitive consequences. Clinical Relevance- This study contributes towards reaching an objective quantifiable and automated assessment of the potential cognitive consequences of pediatric sleep apnea.

Distinctive effects of executive dysfunction and loss of learning/memory abilities on resting-state brain activity.

Dementia is a syndrome characterised by cognitive impairments, with a loss of learning/memory abilities at the earlier stages and executive dysfunction at the later stages. However, recent studies have suggested that impairments in both learning/memory abilities and executive functioning might co-exist. Cognitive impairments have been primarily evaluated using neuropsychological assessments, such as the Mini-Mental State Examination (MMSE). Recently, neuroimaging techniques such as magnetoencephalography (MEG), which assess changes in resting-state brain activity, have also been used as biomarkers for cognitive impairment. However, it is unclear whether these changes reflect dysfunction in executive function as well as learning and memory. In this study, parameters from the MEG for brain activity, MMSE for learning/memory, and Frontal Assessment Battery (FAB) for executive function were compared within 207 individuals. Three MEG parameters were used as representatives of resting-state brain activity: median frequency, individual alpha frequency, and Shannon's spectral entropy. Regression analysis showed that median frequency was predicted by both the MMSE and FAB scores, while individual alpha frequency and Shannon's spectral entropy were predicted by MMSE and FAB scores, respectively. Our results indicate that MEG spectral parameters reflect both learning/memory and executive functions, supporting the utility of MEG as a biomarker of cognitive impairment.

(Attenuated) hallucinations join basic symptoms in a transdiagnostic network cluster analysis.

Hallucinations are considered characteristic symptoms of psychosis and part of the 'psychosis superspectrum' of the Hierarchical Taxonomy Of Psychopathology (HiTOP) initiative. To gain insight into their psychopathological relevance, we studied their dimensional placement within a single dense transdiagnostic network constituting of basic symptoms as well as of attenuated and frank psychotic, and related symptoms. Newman's modularity analysis was used to detect symptom clusters in an earlier generated network (Jimeno, N., et al., 2020. Main symptomatic treatment targets in suspected and early psychosis: New insights from network analysis. Schizophr. Bull. 46, 884-895. https://doi.org/10.1093/schbul/sbz140). The constituting 86 symptoms were assessed with the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Psychosis-Risk Syndromes (SIPS), and the Positive And Negative Syndrome Scale (PANSS) in three adult samples of an early detection service: clinical high-risk (n = 203), first-episode psychosis (n = 153), and major depression (n = 104). Three clusters were detected: "subjective disturbances", "positive symptoms and behaviors", and "negative and anxious-depressive symptoms". The predominately attenuated hallucinations of both SIPS and PANSS joined the basic symptoms in "subjective disturbances", whereas other positive symptoms entered "positive symptoms and behaviors". Our results underline the importance of insight in separating true psychotic hallucinations from other hallucinatory experiences that, albeit phenomenologically similar are still experienced with some insight, i.e., are present in an attenuated form. We conclude that, strictly, hallucinations held with any degree of insight should not be used to diagnose transition to or presence of frank psychoses and, relatedly, to justify antipsychotic medication.

Schizophrenia induces abnormal frequency-dependent patterns of dynamic brain network reconfiguration during an auditory oddball task.

Objective.Schizophrenia is a psychiatric disorder that has been shown to disturb the dynamic top-down processing of sensory information. Various imaging techniques have revealed abnormalities in brain activity associated with this disorder, both locally and between cerebral regions. However, there is increasing interest in investigating dynamic network response to novel and relevant events at the network level during an attention-demanding task with high-temporal-resolution techniques. The aim of the work was: (i) to test the capacity of a novel algorithm to detect recurrent brain meta-states from auditory oddball task recordings; and (ii) to evaluate how the dynamic activation and behavior of the aforementioned meta-states were altered in schizophrenia, since it has been shown to impair top-down processing of sensory information.Approach.A novel unsupervised method for the detection of brain meta-states based on recurrence plots and community detection algorithms, previously tested on resting-state data, was used on auditory oddball task recordings. Brain meta-states and several properties related to their activation during target trials in the task were extracted from electroencephalography data from patients with schizophrenia and cognitively healthy controls.Main results.The methodology successfully detected meta-states during an auditory oddball task, and they appeared to show both frequency-dependent time-locked and non-time-locked activity with respect to the stimulus onset. Moreover, patients with schizophrenia displayed higher network diversity, and showed more sluggish meta-state transitions, reflected in increased dwell times, less complex meta-state sequences, decreased meta-state space speed, and abnormal ratio of negative meta-state correlations.Significance.Abnormal cognition in schizophrenia is also reflected in decreased brain flexibility at the dynamic network level, which may hamper top-down processing, possibly indicating impaired decision-making linked to dysfunctional predictive coding. Moreover, the results showed the ability of the methodology to find meaningful and task-relevant changes in dynamic connectivity and pathology-related group differences.

Effect of segment length, sampling frequency, and imaging modality on the estimation of measures of brain meta-state activation: an MEG/EEG study.

The main objective of this study was to examine the influence that recording length, sampling frequency, and imaging modality have on the estimation and characterization of spontaneous brain meta-states during rest. To this end, a recently developed method of meta-state extraction and characterization was applied to a subset of 16 healthy elderly subjects from two independent electroencephalographic and magnetoencephalographic (EEG/MEG) databases. The recordings were segmented into the first 5, 10, 15, 20, 25, 30, 60 and 90-s of artifact-free activity and meta-states were extracted. Temporal activation sequence (TAS) complexity, which characterizes the complexity of the metastateactivation sequences during rest, was calculated. Then, its stability as a function of segment length, sampling frequency, and imaging modality was assessed. The results showed that, in general, the minimum segment length needed to fully characterize resting-state meta-state activation complexity ranged from 15 to 25 seconds. Moreover, it was found that the sampling frequency has a slight influence on the complexity measure, and that results were similar across EEG and MEG. The findings indicate that the proposed methodology can be applied to both EEG and MEG recordings and displays stable behavior with relatively short segments. However, methodological choices, such as sampling frequency, should be carefully considered.

High Frequential Resolution Networks: Considerations on a New Functional Brain Connectivity Framework.

Connectivity analyses are widely used to assess the interaction brain networks. This type of analyses is usually conducted considering the well-known classical frequency bands: delta, theta, alpha, beta, and gamma. However, this parcellation of the frequency content can bias the analyses, since it does not consider the between-subject variability or the particular idiosyncrasies of the connectivity patterns that occur within a band. In this study, we addressed these limitations by introducing the High Frequential Resolution Networks (HFRNs). HFRNs were constructed, using a narrow-bandwidth FIR bank filter of 1 Hz bandwidth, for two different connectivity metrics (Amplitude Envelope Correlation, AEC, and Phase Lag index, PLI) and for 3 different databases of MEG and EEG recordings. Results showed a noticeable similarity between the frequential evolution of PLI, AEC, and the Power Spectral Density (PSD) from MEG and EEG signals. Nonetheless, some technical remarks should be considered: (i) results at the gamma band should exclude the frequency range around 50 Hz due to abnormal connectivity patterns, consequence of the previously applied 50 Hz notch-filter; (ii) HFRNs patterns barely vary with the connection distance; and (iii) a low sampling frequency can exert a remarkable influence on HFRNs. To conclude, we proposed a new framework to perform connectivity analyses that allow to further analyze the frequency-based distribution of brain networks.

Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker.

Pediatric obstructive sleep apnea (OSA) is a prevalent disorder that disrupts sleep and is associated with neurocognitive and behavioral negative consequences, potentially hampering the development of children for years. However, its relationships with sleep electroencephalogram (EEG) have been scarcely investigated. Here, our main objective was to characterize the overnight EEG of OSA-affected children and its putative relationships with polysomnographic measures and cognitive functions. A two-step analysis involving 294 children (176 controls, 57% males, age range: 5-9 years) was conducted for this purpose. First, the activity and irregularity of overnight EEG spectrum were characterized in the typical frequency bands by means of relative spectral power and spectral entropy, respectively: δ1 (0.1-2 Hz), δ2 (2-4 Hz), θ (4-8 Hz), α (8-13 Hz), σ (10-16 Hz), ß1 (13-19 Hz), ß2 (19-30 Hz), and γ (30-70 Hz). Then, a correlation network analysis was conducted to evaluate relationships between them, six polysomnography variables (apnea-hypopnea index, respiratory arousal index, spontaneous arousal index, overnight minimum blood oxygen saturation, wake time after sleep onset, and sleep efficiency), and six cognitive scores (differential ability scales, Peabody picture vocabulary test, expressive vocabulary test, design copying, phonological processing, and tower test). We found that as the severity of the disease increases, OSA broadly affects sleep EEG to the point that the information from the different frequency bands becomes more similar, regardless of activity or irregularity. EEG activity and irregularity information from the most severely affected children were significantly associated with polysomnographic variables, which were coherent with both micro and macro sleep disruptions. We hypothesize that the EEG changes caused by OSA could be related to the occurrence of respiratory-related arousals, as well as thalamic inhibition in the slow oscillation generation due to increases in arousal levels aimed at recovery from respiratory events. Furthermore, relationships between sleep EEG and cognitive scores emerged regarding language, visual-spatial processing, and executive function with pronounced associations found with EEG irregularity in δ1 (Peabody picture vocabulary test and expressive vocabulary test maximum absolute correlations 0.61 and 0.54) and ß2 (phonological processing, 0.74; design copying, 0.65; and Tow 0.52). Our results show that overnight EEG informs both sleep alterations and cognitive effects of pediatric OSA. Moreover, EEG irregularity provides new information that complements and expands the classic EEG activity analysis. These findings lay the foundation for the use of sleep EEG to assess cognitive changes in pediatric OSA.

Influence of PICALM and CLU risk variants on beta EEG activity in Alzheimer's disease patients.

PICALM and CLU genes have been linked to alterations in brain biochemical processes that may have an impact on Alzheimer's disease (AD) development and neurophysiological dynamics. The aim of this study is to analyze the relationship between the electroencephalographic (EEG) activity and the PICALM and CLU alleles described as conferring risk or protective effects on AD patients and healthy controls. For this purpose, EEG activity was acquired from: 18 AD patients and 12 controls carrying risk alleles of both PICALM and CLU genes, and 35 AD patients and 12 controls carrying both protective alleles. Relative power (RP) in the conventional EEG frequency bands (delta, theta, alpha, beta, and gamma) was computed to quantify the brain activity at source level. In addition, spatial entropy (SE) was calculated in each band to characterize the regional distribution of the RP values throughout the brain. Statistically significant differences in global RP and SE at beta band (p-values < 0.05, Mann-Whitney U-test) were found between genotypes in the AD group. Furthermore, RP showed statistically significant differences in 58 cortical regions out of the 68 analyzed in AD. No statistically significant differences were found in the control group at any frequency band. Our results suggest that PICALM and CLU AD-inducing genotypes are involved in physiological processes related to disruption in beta power, which may be associated with physiological disturbances such as alterations in beta-amyloid and neurotransmitter metabolism.

Entropy in Brain Networks.

A thorough and comprehensive understanding of the human brain ultimately depends on knowledge of large-scale brain organization[...].

The Menstrual Cycle Alters Resting-State Cortical Activity: A Magnetoencephalography Study.

Resting-state neural oscillations are used as biomarkers for functional diseases such as dementia, epilepsy, and stroke. However, accurate interpretation of clinical outcomes requires the identification and minimisation of potential confounding factors. While several studies have indicated that the menstrual cycle also alters brain activity, most of these studies were based on visual inspection rather than objective quantitative measures. In the present study, we aimed to clarify the effect of the menstrual cycle on spontaneous neural oscillations based on quantitative magnetoencephalography (MEG) parameters. Resting-state MEG activity was recorded from 25 healthy women with normal menstrual cycles. For each woman, resting-state brain activity was acquired twice using MEG: once during their menstrual period (MP) and once outside of this period (OP). Our results indicated that the median frequency and peak alpha frequency of the power spectrum were low, whereas Shannon spectral entropy was high, during the MP. Theta intensity within the right temporal cortex and right limbic system was significantly lower during the MP than during the OP. High gamma intensity in the left parietal cortex was also significantly lower during the MP than during the OP. Similar differences were also observed in the parietal and occipital regions between the proliferative (the late part of the follicular phase) and secretory phases (luteal phase). Our findings suggest that the menstrual cycle should be considered to ensure accurate interpretation of functional neuroimaging in clinical practice.

Exploring the Interactions Between Neurophysiology and Cognitive and Behavioral Changes Induced by a Non-pharmacological Treatment: A Network Approach.

Dementia due to Alzheimer's disease (AD) is a neurological syndrome which has an increasing impact on society, provoking behavioral, cognitive, and functional impairments. AD lacks an effective pharmacological intervention; thereby, non-pharmacological treatments (NPTs) play an important role, as they have been proven to ameliorate AD symptoms. Nevertheless, results associated with NPTs are patient-dependent, and new tools are needed to predict their outcome and to improve their effectiveness. In the present study, 19 patients with AD underwent an NPT for 83.1 ± 38.9 days (mean ± standard deviation). The NPT was a personalized intervention with physical, cognitive, and memory stimulation. The magnetoencephalographic activity was recorded at the beginning and at the end of the NPT to evaluate the neurophysiological state of each patient. Additionally, the cognitive (assessed by means of the Mini-Mental State Examination, MMSE) and behavioral (assessed in terms of the Dementia Behavior Disturbance Scale, DBD-13) status were collected before and after the NPT. We analyzed the interactions between cognitive, behavioral, and neurophysiological data by generating diverse association networks, able to intuitively characterize the relationships between variables of a different nature. Our results suggest that the NPT remarkably changed the structure of the association network, reinforcing the interactions between the DBD-13 and the neurophysiological parameters. We also found that the changes in cognition and behavior are related to the changes in spectral-based neurophysiological parameters. Furthermore, our results support the idea that MEG-derived parameters can predict NPT outcome; specifically, a lesser degree of AD neurophysiological alterations (i.e., neural oscillatory slowing, decreased variety of spectral components, and increased neural signal regularity) predicts a better NPT prognosis. This study provides deeper insights into the relationships between neurophysiology and both, cognitive and behavioral status, proving the potential of network-based methodology as a tool to further understand the complex interactions elicited by NPTs.

The association between carotid blood flow and resting-state brain activity in patients with cerebrovascular diseases.

Cerebral hypoperfusion impairs brain activity and leads to cognitive impairment. Left and right common carotid arteries (CCA) are the major source of cerebral blood supply. It remains unclear whether blood flow in both CCA contributes equally to brain activity. Here, CCA blood flow was evaluated using ultrasonography in 23 patients with cerebrovascular diseases. Resting-state brain activity and cognitive status were also assessed using magnetoencephalography and a cognitive subscale of the Functional Independence Measure, respectively, to explore the relationships between blood flow, functional brain activity, and cognitive status. Our findings indicated that there was an association between blood flow and resting-state brain activity, and between resting-state brain activity and cognitive status. However, blood flow was not significantly associated with cognitive status directly. Furthermore, blood velocity in the right CCA correlated with resting-state brain activity, but not with the resistance index. In contrast, the resistance index in the left CCA correlated with resting-state brain activity, but not with blood velocity. Our findings suggest that hypoperfusion is important in the right CCA, whereas cerebral microcirculation is important in the left CCA for brain activity. Hence, this asymmetry should be considered when designing appropriate therapeutic strategies.

Exploring the Alterations in the Distribution of Neural Network Weights in Dementia Due to Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder which has become an outstanding social problem. The main objective of this study was to evaluate the alterations that dementia due to AD elicits in the distribution of functional network weights. Functional connectivity networks were obtained using the orthogonalized Amplitude Envelope Correlation (AEC), computed from source-reconstructed resting-state eletroencephalographic (EEG) data in a population formed by 45 cognitive healthy elderly controls, 69 mild cognitive impaired (MCI) patients and 81 AD patients. Our results indicated that AD induces a progressive alteration of network weights distribution; specifically, the Shannon entropy (SE) of the weights distribution showed statistically significant between-group differences (p < 0.05, Kruskal-Wallis test, False Discovery Rate corrected). Furthermore, an in-depth analysis of network weights distributions was performed in delta, alpha, and beta-1 frequency bands to discriminate the weight ranges showing statistical differences in SE. Our results showed that lower and higher weights were more affected by the disease, whereas mid-range connections remained unchanged. These findings support the importance of performing detailed analyses of the network weights distribution to further understand the impact of AD progression on functional brain activity.