Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer's disease.

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer's disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Resting State Alpha Electroencephalographic Rhythms Are Affected by Sex in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment: A Retrospective and Exploratory Study.

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aß42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.

Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

Resting state electroencephalographic alpha rhythms are sensitive to Alzheimer's disease mild cognitive impairment progression at a 6-month follow-up.

Are posterior resting-state electroencephalographic (rsEEG) alpha rhythms sensitive to the Alzheimer's disease mild cognitive impairment (ADMCI) progression at a 6-month follow-up? Clinical, cerebrospinal, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 Healthy old seniors (equivalent groups for demographic features) were available from an international archive (www.pdwaves.eu). The ADMCI patients were arbitrarily divided into two groups: REACTIVE and UNREACTIVE, based on the reduction (reactivity) in the posterior rsEEG alpha eLORETA source activities from the eyes-closed to eyes-open condition at ≥ -10% and -10%, respectively. 75% of the ADMCI patients were REACTIVE. Compared to the UNREACTIVE group, the REACTIVE group showed (1) less abnormal posterior rsEEG source activity during the eyes-closed condition and (2) a decrease in that activity at the 6-month follow-up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. Such a biomarker might reflect abnormalities in cortical arousal in quiet wakefulness to be used for clinical studies in ADMCI patients using 6-month follow-ups.

Poor reactivity of posterior electroencephalographic alpha rhythms during the eyes open condition in patients with dementia due to Parkinson's disease.

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.

Parietal intrahemispheric source connectivity of resting-state electroencephalographic alpha rhythms is abnormal in Naïve HIV patients.

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8-12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder. The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals. Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals. In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Reactivity of posterior cortical electroencephalographic alpha rhythms during eyes opening in cognitively intact older adults and patients with dementia due to Alzheimer's and Lewy body diseases.

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients.

Resting-state electroencephalographic delta rhythms may reflect global cortical arousal in healthy old seniors and patients with Alzheimer's disease dementia.

Extending Basar's theory of event-related EEG oscillations, here we hypothesize that even in quiet wakefulness, transient increases in delta rhythms may enhance global cortical arousal as revealed by the desynchronization of alpha rhythms in normal (Nold) seniors with some derangement in Alzheimer's disease dementia (ADD). Clinical and EEG datasets in 100 ADD and 100 Nold individuals matched as demography, education, and gender were taken from an international archive. Standard delta (< 4 Hz) and alpha1 (8-10.5 Hz) bands were used for the main analysis, while alpha2 (10.5-13 Hz), theta (4-8 Hz), beta1 (13-20 Hz), beta2 (20-35 Hz), and gamma (35-40 Hz) served as controls. In the interpretation, the higher the alpha1 power (density), the lower that arousal. As expected, when compared to the Nold group, the ADD group showed higher global (scalp) power density at the delta-theta band and lower global power density at the alpha-beta bands. As novel findings, we observed that: (1) in the Nold group, the global delta and alpha1-2 power were negatively and linearly correlated; (2) in the ADD group, this correlation was just marginal; and (3) in both Nold and AD groups, the EEG epochs with the highest delta power (median value for stratification) were associated with the lowest global alpha1 power. This effect was related to eLORETA freeware solutions showing maximum alpha1 source activations in posterior cortical regions. These results suggest that even in quiet wakefulness, delta and alpha rhythms are related to each other, and ADD partially affects this cross-band neurophysiological mechanism.

Abnormal cortical neural synchronization mechanisms in quiet wakefulness are related to motor deficits, cognitive symptoms, and visual hallucinations in Parkinson's disease patients: an electroencephalographic study.

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N = 136) and Alzheimer's disease patients (AD, N = 85), and healthy older participants (Nold, N = 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness.

Abnormalities of Cortical Sources of Resting State Delta Electroencephalographic Rhythms Are Related to Epileptiform Activity in Patients With Amnesic Mild Cognitive Impairment Not Due to Alzheimer's Disease.

In the present exploratory and retrospective study, we hypothesized that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might be more abnormal in patients with epileptiform EEG activity (spike-sharp wave discharges, giant spikes) and amnesic mild cognitive impairment not due to Alzheimer's disease (noADMCI-EEA) than matched noADMCI patients without EEA (noADMCI-noEEA). Clinical, neuroimaging, neuropsychological, and rsEEG data in 32 noADMCI and 30 normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were carefully matched among them. No subject had received a clinical diagnosis of epilepsy. Individual alpha frequency peak (IAF) was used to determine the delta, theta, and alpha frequency bands of rsEEG rhythms. Fixed beta and gamma bands were also considered. Regional rsEEG cortical sources were estimated by eLORETA freeware. Area under receiver operating characteristic (AUROC) curves indexed the accuracy of eLORETA solutions in the classification between noADMCI-EEA and noADMCI-noEEA individuals. As novel findings, EEA was observed in 41% of noADMCI patients. Furthermore, these noADMCI-EEA patients showed higher temporal delta source activities as compared to noADMCI-no EEA patients and Nold subjects. Those activities discriminated individuals of the two NoADMCI groups with an accuracy of about 70%. The significant percentage of noADMCI-EEA patients showing EEA and marked abnormalities in temporal rsEEG rhythms at delta frequencies suggest a substantial role of underlying neural hypersynchronization mechanisms in their brain dysfunctions.

Abnormalities of resting-state EEG in patients with prodromal and overt dementia with Lewy bodies: Relation to clinical symptoms.

OBJECTIVE: Here we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms. METHODS: We extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer's disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources. RESULTS: As compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB "controls", the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005). CONCLUSIONS: Relevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients. SIGNIFICANCE: Those features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies.

Sleep deprivation and Modafinil affect cortical sources of resting state electroencephalographic rhythms in healthy young adults.

OBJECTIVE: It has been reported that sleep deprivation affects the neurophysiological mechanisms underpinning the vigilance. Here, we tested the following hypotheses in the PharmaCog project (www.pharmacog.org): (i) sleep deprivation may alter posterior cortical delta and alpha sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms in healthy young adults; (ii) after the sleep deprivation, a vigilance enhancer may recover those rsEEG source markers. METHODS: rsEEG data were recorded in 36 healthy young adults before (Pre-sleep deprivation) and after (Post-sleep deprivation) one night of sleep deprivation. In the Post-sleep deprivation, these data were collected after a single dose of PLACEBO or MODAFINIL. rsEEG cortical sources were estimated by eLORETA freeware. RESULTS: In the PLACEBO condition, the sleep deprivation induced an increase and a decrease in posterior delta (2-4 Hz) and alpha (8-13 Hz) source activities, respectively. In the MODAFINIL condition, the vigilance enhancer partially recovered those source activities. CONCLUSIONS: The present results suggest that posterior delta and alpha source activities may be both related to the regulation of human brain arousal and vigilance in quiet wakefulness. SIGNIFICANCE: Future research in healthy young adults may use this methodology to preselect new symptomatic drug candidates designed to normalize brain arousal and vigilance in seniors with dementia.

Abnormalities of Resting State Cortical EEG Rhythms in Subjects with Mild Cognitive Impairment Due to Alzheimer's and Lewy Body Diseases.

The present study tested the hypothesis that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and dementia with Lewy bodies (DLBMCI) as compared to cognitively normal elderly (Nold) subjects. Clinical and rsEEG data in 30 ADMCI, 23 DLBMCI, and 30 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) score was matched between the ADMCI and DLBMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROCC) classified these sources across individuals. Compared to Nold, IAF showed marked slowing in DLBMCI and moderate in ADMCI. Furthermore, the posterior alpha 2 and alpha 3 source activities were more abnormal in the ADMCI than the DLBMCI group, while widespread delta source activities were more abnormal in the DLBMCI than the ADMCI group. The posterior delta and alpha sources correlated with the MMSE score and correctly classified the Nold and MCI individuals (area under the ROCC >0.85). In conclusion, the ADMCI and DLBMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test the clinical validity of these rsEEG markers.

Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients with Mild Cognitive Impairment due to Alzheimer's and Chronic Kidney Diseases: An EEG Study.

This study tested whether resting state alpha rhythms (8-13 Hz) may characterize mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (<4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery.

Abnormalities of cortical neural synchronization mechanisms in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study.

The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to Alzheimer's disease dementia (ADD), Parkinson's disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini-Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.