Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson's and Lewy body diseases

AbstractBackgroundParkinson's disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations.MethodClinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer's disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.ResultAs a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2).ConclusionThese novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy

Functional cortical source connectivity of resting state electroencephalographic alpha rhythms shows similar abnormalities in patients with mild cognitive impairment due to Alzheimer's and Parkinson's diseases

Objective: This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimer's (ADMCI) and Parkinson's (PDMCI) diseases compared to healthy elderly subjects (Nold). Methods: rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals. Results: Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups. Conclusions: These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels. Significance: The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved

Neurophysiological mechanisms of quiet vigilance in neurodegenerative diseases: an electroencephalography research program

In the field of neurophysiological research, the term vigilance refers to a variety of mental states of monitoring of external world during wakefulness, related to activities in brain circuits (Steriade, 1999), projections of ascending reticular activating systems (ARASs) using dopaminergic, noradrenergic, serotonergic, histaminergic, cholinergic, and glutamatergic neurotransmitters (Moruzzi and Magoun, 1949). Malfunctioning of these neuromodulatory circuits may cause a variety of behavioural and cognitive dysfunctions as those observed in the most common progressive neurodegenerative dementing disorders such as Alzheimer’s (AD), Parkinson’s (PD), and Lewy Bodies diseases (DLB; Berridge et al., 2003; Gratwicke et al., 2015). AD, PD and DLB suffer of a progressive loss of cognitive functions. Typical clinical manifestation of AD is severe deficits in episodic memory while PD and DLB are both characterized by frontal executive deficits and motor symptoms (Alzheimer’s society 2017; McKeith et al., 2004). Compared with AD and PD patients, DLB patients have more frequent neuropsychiatric symptoms such as psychosis, depression, apathy and abnormalities in sleep behavior (Aarsland et al., 2005). However, there is limited information regarding the prodromal state of these type of dementia, and it need of a clinical markers to support decision-making processes underlying clinical management of AD, PD and DLB patients. The electroencephalography in resting-state condition (rsEEG) can be a valid candidate for this purpose as it can probe cortical arousal in quiet wakefulness, as revealed by the effects of the administration of a pharmacological agent enhancing vigilance (i.e., modafinil) and sleep deprivation on the regulation of brain rsEEG rhythms in humans (Del Percio et al., 2019). The aim of this PhD thesis was to improve our understanding of neurophysiological correlates of the quiet vigilance in patients with the most prevalent neurodegenerative dementing disorders such as AD, PD, and DLB. This aim was pursued by three retrospective rsEEG studies developed in the international clinical and EEG databases of High-resolution EEG Laboratory at the Department of Physiology and Pharmacology “V. Erspamer” at Sapienza University of Rome. These studies were developed in cooperation with the Partners of European Consortium of DLB. In the first study, we tested the hypothesis that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect cortical arousal in patients with dementia due to AD (ADD), PD (PDD), and Lewy body disease (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were extracted from our 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 (< 4 Hz), theta (3-5 Hz), alpha1 (5-7 Hz), alpha2 (7-9 Hz), and alpha3 (9-13 Hz) frequency bands. Fixed beta1 (14-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz) frequency bands were also considered. The 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. Results were quite interesting at both group and individual levels. At the group level, compared to the Nold subjects, IAF showed marked slowing in the PDD and DLB patients and moderate slowing in the ADD patients. Furthermore, all patient groups over the Nold subjects showed lower posterior alpha 2 source activities. This effect was dramatic in the ADD, marked in the DLB, and moderate in the PDD patients. These groups of patients also showed higher occipital delta source activities, but this effect was dramatic in the PDD, marked in the DLB, and moderate in the ADD patients. At the individual level, 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. We concluded that in quiet vigilance, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. In the second study, we hypothesized that PD patients may show peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations), reflected in rsEEG rhythms. Clinical and rsEEG rhythms in age-, sex-, and education-matched PD (N = 93), AD (N= 70), and Nold (N = 60) subjects were available from the same international archive of the first study. The same methodology for EEG sources estimation was applied as well. Results showed that: (1) compared to the Nold subjects, 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 delta and 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 parieto-occipital alpha sources activities. These results suggest that in PD patients resting in quiet vigilance, abnormalities in cortical neural synchronization at delta and alpha frequencies are differently related to cognitive, motor, and visual hallucinations. The third study tested if cortical sources of rsEEG rhythms may differ as a function of different clinical symptoms in sub-groups of patients with dementia with DLB. Clinical and rsEEG rhythms in age-, sex-, and education-were matched in DLB (N=46), AD (N=60), and Nold (N=20) subjects. Results showed that compared with the Nold subjects, the DLB and AD patients exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). In relation to the DLB controls, the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower delta and alpha source activities in widespread posterior cortical regions; (2) greater cognitive deficits exhibited higher delta source activities posteriorly; (3) visual hallucinations pointed to greater parieto-frontal delta and parietal alpha source activities; (4) cognitive fluctuations manifested higher parietal alpha source activities. These rsEEG results suggest that when prominent, any clinical feature was associated with a different topography of delta and alpha source activities in the DLB patients. In conclusion, the three studies unveiled specific abnormalities in rsEEG rhythms at delta and alpha frequencies in AD, PD, and DLB patients experiencing quiet vigilance. These effects may represent the neurophysiological correlates of abnormalities in ARASs, cortical arousal, and cholinergic and dopaminergic systems probed by EEG techniques in AD, PD, and DLB patients. These effects were strictly related to clinical manifestations of the mentioned diseases. Future studies may cross-validate those results in prospective, harmonized rsEEG studies in AD, PD, and DLB patients followed from prodromal to dementia stages of the diseases

Corrigendum: Football Players Do Not Show "Neural Efficiency" in Cortical Activity Related to Visuospatial Information Processing During Football Scenes: An EEG Mapping Study

[This corrects the article DOI: 10.3389/fpsyg.2019.00890.]

Prevalence and associations of symptoms of upper extremities, repetitive strain injuries (RSI) and 'RSI-like condition'. A cross sectional study of bank workers in Northeast Brazil.

BACKGROUND: The repetitive strain injury syndrome (RSI) is a worldwide occupational health problem affecting all types of economic activities. We investigated the prevalence and some risk factors for RSI and related conditions, namely 'symptoms of upper limbs' and 'RSI-like condition'. METHODS: We conducted a cross-sectional study with 395 bank workers in Recife, Northeast Brazil. Symptoms of upper limbs and 'RSI-like condition' were assessed by a simple questionnaire, which was used to screen probable cases of RSI. The diagnosis of RSI was confirmed by clinical examination. The associations of potential risk factors and the outcomes were assessed by multiple logistic regression analysis. RESULTS: We found prevalence rates of 56% for symptoms of the upper limbs and 30% for 'RSI-like condition'. The estimated prevalence of clinically confirmed cases of RSI was 22%. Female sex and occupation (as cashier or clerk) increased the risk of all conditions, but the associations were stronger for cases of RSI than for less specific diagnoses of 'RSI-like condition' and symptoms of upper limbs. Age was inversely related to the risk of symptoms of upper limbs but not to 'RSI-like' or RSI. CONCLUSION: The variation in the magnitude of risk according to the outcome assessed suggests that previous studies using different definitions may not be immediately comparable. We propose the use of a simple instrument to screen cases of RSI in population based studies, which still needs to be validated in other populations. The high prevalence of RSI and related conditions in this population suggests the need for urgent interventions to tackle the problem, which could be directed to individuals at higher risk and to changes in the work organization and environment of the general population

Football Players Do Not Show "Neural Efficiency" in Cortical Activity Related to Visuospatial Information Processing During Football Scenes: An EEG Mapping Study

This study tested the hypothesis of cortical neural efficiency (i.e., reduced brain activation in experts) in the visuospatial information processing related to football (soccer) scenes in football players. Electroencephalographic data were recorded from 56 scalp electrodes in 13 football players and eight matched non-players during the observation of 70 videos with football actions lasting 2.5 s each. During these videos, the central fixation target changed color from red to blue or vice versa. The videos were watched two times. One time, the subjects were asked to estimate the distance between players during each action (FOOTBALL condition, visuospatial). Another time, they had to estimate if the fixation target was colored for a longer time in red or blue color (CONTROL condition, non-visuospatial). The order of the two conditions was pseudo-randomized across the subjects. Cortical activity was estimated as the percent reduction in power of scalp alpha rhythms (about 8-12 Hz) during the videos compared with a pre-video baseline (event-related desynchronization, ERD). In the FOOTBALL condition, a prominent and bilateral parietal alpha ERD (i.e., cortical activation) was greater in the football players than non-players (p < 0.05) in contrast with the neural efficiency hypothesis. In the CONTROL condition, no significant alpha ERD difference was observed. No difference in behavioral response time and accuracy was found between the two groups in any condition. In conclusion, a prominent parietal cortical activity related to visuospatial processes during football scenes was greater in the football players over controls in contrast with the neural efficiency hypothesis

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

International audienceObjective: 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

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

Cortical sources of resting state electroencephalographic rhythms probe brain function in naïve HIV individuals

Objective Here we evaluated the hypothesis that resting state electroencephalographic (EEG) cortical sources correlated with cognitive functions and discriminated asymptomatic treatment-naïve HIV subjects (no AIDS). Methods EEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cognitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest. Results Widespread sources of delta (<4 Hz) and alpha (8â\u80\u9312 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p < 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70â\u80\u9375%). Conclusions Regional EEG abnormalities in quiet wakefulness characterized treatment-naïve HIV subjects at the individual level. Significance This EEG approach may contribute to the management of treatment-naïve HIV subjects at risk of cognitive deficits