Derya Durusu Emek-Savaş

Occipital sources of resting-state alpha rhythms are related to local gray matter density in subjects with amnesic mild cognitive impairment and Alzheimer's disease

Occipital sources of resting-state electroencephalographic (EEG) alpha rhythms are abnormal, at the group level, in patients with amnesic mild cognitive impairment (MCI) and Alzheimers disease (AD). Here, we evaluated the hypothesis that amplitude of these occipital sources is related to neurodegeneration in occipital lobe as measured by magnetic resonance imaging. Resting-state eyes-closed EEG rhythms were recorded in 45 healthy elderly (Nold), 100 MCI, and 90 AD subjects. Neurodegeneration of occipital lobe was indexed by weighted averages of gray matter density, estimated from structural MRIs. EEG rhythms of interest were alpha 1 (8-10.5 Hz) and alpha 2 (10.5-13 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. Results showed a positive correlation between occipital gray matter density and amplitude of occipital alpha 1 sources in Nold, MCI, and AD subjects as a whole group (r = 0.3, p = 0.000004, N = 235). Furthermore, there was a positive correlation between the amplitude of occipital alpha 1 sources and cognitive status as revealed by Mini Mental State Examination score across all subjects (r = 0.38, p = 0.000001, N = 235). Finally, amplitude of occipital alpha 1 sources allowed a moderate classification of individual Nold and AD subjects (sensitivity: 87.8%; specificity: 66.7%; area under the receiver operating characteristic curve: 0.81). These results suggest that the amplitude of occipital sources of resting-state alpha rhythms is related to AD neurodegeneration in occipital lobe along pathologic aging.

Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment

The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersens criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15–20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes.

Frontal delta event-related oscillations relate to frontal volume in mild cognitive impairment and healthy controls

Amnesic mild cognitive impairment (MCI) represents a risk of developing Alzheimers disease (AD), but not all MCI subjects progress to dementia of AD type. Magnetic resonance imaging (MRI) of cortical and hippocampal atrophy supports early diagnosis of AD in MCI subjects, while frontal event-related oscillations (EROs) at delta frequencies (<4Hz) are appealing markers for this purpose, as they are both cost-effective and largely available. The present study tested the hypothesis that these EROs reflect cortical frontal neurodegeneration in the continuum between normal and amnesic MCI subjects. EROs and volumetric MRI data were recorded in 28 amnesic MCI and in 28 healthy elderly controls (HCs). EROs were collected during a standard visual oddball paradigm including frequent (66.6%) and rare (33.3%; targets to be mentally counted) stimuli. Peak-to-peak amplitude of delta target EROs (<4Hz) was measured. Volume of frontal cortex was estimated from MRIs. Frontal volume was lower in MCI compared to the HC group. Furthermore, widespread delta target EROs were lower in amplitude in the former than in the latter group. Finally, there was a positive correlation between frontal volume and frontal delta target EROs in MCI and HC subjects as a whole group. These results suggest that frontal delta EROs reflect frontal neurodegeneration in the continuum between normal and amnesic MCI subjects.

Reduced Visual Event-Related Delta Oscillatory Responses in Amnestic Mild Cognitive Impairment

Mild cognitive impairment (MCI) is considered as a prodromal stage for Alzheimers disease (AD) in the majority of cases. Event-related oscillations might be used for detection of cognitive deficits. Our groups earlier results showed diminished delta visual and auditory target oscillatory responses in AD, and we investigated whether this prevails for MCI. Eighteen MCI subjects and 18 age-matched healthy elderly controls were investigated. The maximum peak-to-peak amplitudes of oscillatory responses for each subjects averaged oscillatory target responses in delta, theta, and alpha frequency bands upon application of visual oddball paradigm were measured. Repeated measures of ANOVA was used to analyze four locations (frontal, central, parietal, occipital), at three coronal (left, midline, right) sites. Independent t tests were applied for post-hoc analyses. The oddball target delta response (0.5-3.0 Hz) was 26-32% lower in MCI than healthy controls over fronto-central-parietal regions [F(1.34) = 4.562, p = 0.04]. Without a group effect, theta oscillatory responses (4-7 Hz) showed significant differences in coronal electrodes indicating highest values over mid-electrode sites, and a anteriorposterior x coronal effect, being maximum at mid-central. Alpha frequency band analyses indicated no statistical differences. Peak-to-peak amplitudes of visual target delta oscillatory responses were lower in fronto-central-parietal regions in MCI than in healthy controls. This supports our earlier findings in AD, showing hypoactive delta fronto-central-parietal regions during cognitive tasks. These results indicate that event-related oscillations may detect early changes of brain dynamics in MCI, and deserves to be investigated as a candidate biomarker in further studies using multimodal techniques.

Decrease of delta oscillatory responses is associated with increased age in healthy elderly.

BACKGROUND The purpose of this study was to investigate changes in delta event-related oscillations (EROs) in younger and older healthy elderly subjects. We hypothesized that delta EROs were affected by age-related changes, which could be reflected in a visual oddball paradigm. METHOD The study included two groups of subjects, 17 younger healthy elderly (mean age: 63.1±2.8years) and 17 gender- and education-matched older healthy elderly (mean age: 79.6±5.2years), who performed a visual oddball paradigm. EEG was recorded from F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz and O2 locations. Peak-to-peak amplitudes of delta (0.5-3Hz) target ERO responses during the post-stimulus 0-800ms time window were measured. Repeated measures of ANOVA was used to analyze four locations (frontal, central, parietal, occipital), at three sagittal (left, midline, right) sites. Independent t-tests were applied for post-hoc analyses. RESULTS The older healthy elderly group had 16-25% lower values for the maximum peak-to-peak amplitudes of delta ERO compared with the younger healthy elderly group over frontal (p<0.003), central (p<0.0001) and parietal (p<0.007) locations [F3.96=4.396, p=0.015]. Furthermore, there was a moderate negative correlation between age and Cz peak-to-peak amplitude of target delta responses [r=-0.401, p<0.02], indicating the notion that peak-to-peak amplitude of Cz decreases as age increases. CONCLUSION In the present study younger healthy elderly showed significantly higher event-related delta responses than older healthy elderly at frontal, central and parietal locations. Moreover, delta ERO responses decreased in accordance with age.

Patients with Mild Cognitive Impairment Display Reduced Auditory Event-Related Delta Oscillatory Responses

Background. Event-related oscillations (ERO) may provide a useful tool for the identification of cognitive deficits in mild cognitive impairment (MCI) and Alzheimers disease (AD). In the present study, we investigate peak-to-peak amplitude of auditory event-related delta oscillations of MCI subjects. Method. The study included twenty-two consecutive patients with MCI recruited in neurology clinic and 21 age- and education-matched normal elderly controls. A classical auditory oddball paradigm was used in the experiments. EEG was recorded from F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, and O2 locations. The maximum peak-to-peak amplitudes for each subjects averaged delta response (0.5–2.2 Hz) were measured. Results. The amplitudes between groups differed significantly at the frontal and mid-centroparietal locations. ANOVA on delta responses revealed a significant effect for groups (F(1.41) = 4.84, P = 0.033), indicating a larger delta response for healthy controls than MCI subjects. Post hoc comparisons revealed that peak-to-peak delta response was significantly larger for healthy controls than for MCI over electrode sites F3, Fz, F4, Cz, C4, and Pz. Discussion. Event-related delta frequency band seems to be the most affected oscillatory response in cognitive impairment due to AD. Therefore, it deserves to be investigated as a candidate electrophysiological biomarker in further studies.

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 Alzheimers disease dementia (ADD), Parkinsons 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.

Delay of cognitive gamma responses in Alzheimer's disease.

Event-related oscillations (EROs) reflect cognitive brain dynamics, while sensory-evoked oscillations (SEOs) reflect sensory activities. Previous reports from our lab have shown that those with Alzheimers disease (AD) or mild cognitive impairment (MCI) have decreased activity and/or coherence in delta, theta, alpha and beta cognitive responses. In the current study, we investigated gamma responses in visual SEO and ERO in 15 patients with AD and in 15 age-, gender- and education-matched healthy controls. The following parameters were analyzed over the parietal-occipital regions in both groups: (i) latency of the maximum gamma response over a 0–800 ms time window; (ii) the maximum peak-to-peak amplitudes for each participants averaged SEO and ERO gamma responses in 3 frequency ranges (25–30, 30–35, 40–48 Hz); and (iii) the maximum peak-to-peak amplitudes for each participants averaged SEO and ERO gamma responses over a 0–800 ms time block containing four divided time windows (0–200, 200–400, 400–600, and 600–800 ms). There were main group effects in terms of both latency and peak-to-peak amplitudes of gamma ERO. However, peak-to-peak gamma ERO amplitude differences became noticeable only when the time block was divided into four time windows. SEO amplitudes in the 25–30 Hz frequency range of the 0–200 ms time window over the left hemisphere were greater in the healthy controls than in those with AD. Gamma target ERO latency was delayed up to 138 ms in AD patients when compared to healthy controls. This finding may be an effect of lagged neural signaling in cognitive circuits, which is reflected by the delayed gamma responses in those with AD. Based on the results of this study, we propose that gamma responses should be examined in a more detailed fashion using multiple frequency and time windows.

Abnormalities of Cortical Neural Synchronization Mechanisms in Subjects with Mild Cognitive Impairment due to Alzheimer's and Parkinson's Diseases: An EEG Study

The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimers disease (ADMCI) and Parkinsons disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (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) was matched between the ADMCI and PDMCI 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 (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC = 0.77-0.79). In conclusion, the PDMCI and ADMCI 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 these rsEEG markers for clinical applications and drug discovery.

The visual cognitive network, but not the visual sensory network, is affected in amnestic mild cognitive impairment: a study of brain oscillatory responses.

Mild Cognitive Impairment (MCI) is considered in many as prodromal stage of Alzheimers disease (AD). Event-related oscillations (ERO) reflect cognitive responses of brain whereas sensory-evoked oscillations (SEO) inform about sensory responses. For this study, we compared visual SEO and ERO responses in MCI to explore brain dynamics (BACKGROUND). Forty-three patients with MCI (mean age=74.0 year) and 41 age- and education-matched healthy-elderly controls (HC) (mean age=71.1 year) participated in the study. The maximum peak-to-peak amplitudes for each subjects averaged delta response (0.5-3.0 Hz) were measured from two conditions (simple visual stimulation and classical visual oddball paradigm target stimulation) (METHOD). Overall, amplitudes of target ERO responses were higher than SEO amplitudes. The preferential location for maximum amplitude values was frontal lobe for ERO and occipital lobe for SEO. The ANOVA for delta responses showed significant results for the group Xparadigm. Post-hoc tests indicated that (1) the difference between groups were significant for target delta responses, but not for SEO, (2) ERO elicited higher responses for HC than MCI patients, and (3) females had higher target ERO than males and this difference was pronounced in the control group (RESULTS). Overall, cognitive responses display almost double the amplitudes of sensory responses over frontal regions. The topography of oscillatory responses differs depending on stimuli: visualsensory responses are highest over occipitals and -cognitive responses over frontal regions. A group effect is observed in MCI indicating that visual sensory and cognitive circuits behave differently indicating preserved visual sensory responses, but decreased cognitive responses (CONCLUSION).