International Federation of Clinical Neurophysiology (IFCN) - EEG research workgroup: Recommendations on frequency and topographic analysis of resting state EEG rhythms. Part 1: Applications in clinical research studies.

In 1999, the International Federation of Clinical Neurophysiology (IFCN) published "IFCN Guidelines for topographic and frequency analysis of EEGs and EPs" (Nuwer et al., 1999). Here a Workgroup of IFCN experts presents unanimous recommendations on the following procedures relevant for the topographic and frequency analysis of resting state EEGs (rsEEGs) in clinical research defined as neurophysiological experimental studies carried out in neurological and psychiatric patients: (1) recording of rsEEGs (environmental conditions and instructions to participants; montage of the EEG electrodes; recording settings); (2) digital storage of rsEEG and control data; (3) computerized visualization of rsEEGs and control data (identification of artifacts and neuropathological rsEEG waveforms); (4) extraction of "synchronization" features based on frequency analysis (band-pass filtering and computation of rsEEG amplitude/power density spectrum); (5) extraction of "connectivity" features based on frequency analysis (linear and nonlinear measures); (6) extraction of "topographic" features (topographic mapping; cortical source mapping; estimation of scalp current density and dura surface potential; cortical connectivity mapping), and (7) statistical analysis and neurophysiological interpretation of those rsEEG features. As core outcomes, the IFCN Workgroup endorsed the use of the most promising "synchronization" and "connectivity" features for clinical research, carefully considering the limitations discussed in this paper. The Workgroup also encourages more experimental (i.e. simulation studies) and clinical research within international initiatives (i.e., shared software platforms and databases) facing the open controversies about electrode montages and linear vs. nonlinear and electrode vs. source levels of those analyses.

Cognitive Impairment in Parkinson's Disease Is Reflected with Gradual Decrease of EEG Delta Responses during Auditory Discrimination.

Parkinson's disease (PD) is a neurodegenerative disease that is characterized by loss of dopaminergic neurons in the substantia nigra. Mild Cognitive impairment (MCI) and dementia may come along with the disease. New indicators are necessary for detecting patients that are likely to develop dementia. Electroencephalogram (EEG) Delta responses are one of the essential electrophysiological indicators that could show the cognitive decline. Many research in literature showed an increase of delta responses with the increased cognitive load. Furthermore, delta responses were decreased in MCI and Alzheimer disease in comparison to healthy controls during cognitive paradigms. There was no previous study that analyzed the delta responses in PD patients with cognitive deficits. The present study aims to fulfill this important gap. 32 patients with Parkinson's disease (12 of them were without any cognitive deficits, 10 of them were PD with MCI, and 10 of them were PD with dementia) and 16 healthy subjects were included in the study. Auditory simple stimuli and Auditory Oddball Paradigms were applied. The maximum amplitudes of each subject's delta response (0.5-3.5 Hz) in 0-600 ms were measured for each electrode and for each stimulation. There was a significant stimulation × group effect [F(df = 6,88) = 3,21; p < 0.015; [Formula: see text] = 0.180], which showed that the difference between groups was specific to the stimulation. Patients with Parkinson's disease (including PD without cognitive deficit, PD with MCI, and PD with dementia) had reduced delta responses than healthy controls upon presentation of target stimulation (p < 0.05, for all comparisons). On the other hand, this was not the case for non-target and simple auditory stimulation. Furthermore, delta responses gradually decrease according to the cognitive impairment in patients with PD. Conclusion: The results of the present study showed that cognitive decline in PD could be represented with decreased event related delta responses during cognitive stimulations. Furthermore, the present study once more strengthens the hypothesis that decrease of delta oscillatory responses could be the candidate of a general electrophysiological indicator for cognitive impairment.

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.

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.

Abnormalities of resting-state functional cortical connectivity in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study.

Previous evidence showed abnormal posterior sources of resting-state delta (<4 Hz) and alpha (8-12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a "disconnection cortical syndrome", in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Nold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values >0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels.

Affective pictures processing is reflected by an increased long-distance EEG connectivity.

Analysis of affective picture processing by means of EEG has invaded the literature. The methodology of event-related EEG coherence is one of the essential methods used to analyze functional connectivity. The aims of the present study are to find out the long range EEG connectivity changes in perception of different affective pictures and analyze gender differences in these long range connected networks. EEGs of 28 healthy subjects (14 female) were recorded at 32 locations. The participants passively viewed emotional pictures (IAPS, unpleasant, pleasant, neutral). The long-distance intra-hemispheric event-related coherence was analyzed for delta (1-3.5 Hz), theta (4-7.5 Hz), and alpha (8-13 Hz) frequency ranges for F3-T7, F4-T8, F3-TP7, F4-TP8, F3-P3, F4-P4, F3-O1, F4-O2, C3-O1, C4-O2 electrode pairs. Unpleasant pictures elicited significantly higher delta coherence values than neutral pictures (p < 0.05), over fronto-parietal, fronto-occipital, and centro-occipital electrode pairs. Furthermore, unpleasant pictures elicited higher theta coherence values than pleasant (p < 0.05) and neutral pictures (p < 0.05). The present study showed that female subjects had higher delta (p < 0.05) and theta (p < 0.05) coherence values than male subjects. This difference was observed more for emotional pictures than for neutral pictures. This study showed that the brain connectivity was higher during emotional pictures than neutral pictures. Females had higher connectivity between different parts of the brain than males during emotional processes. According to these results, we may comment that increased valence and arousal caused increased brain activity. It seems that not just single sources but functional networks were also activated during perception of emotional pictures.

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 Alzheimer's disease (ADMCI) and Parkinson's 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.

Increased long distance event-related gamma band connectivity in Alzheimer's disease.

BACKGROUND: Brain oscillatory responses can be used for non-invasive analyses of cortico-cortical connectivity, local neuronal synchronization, and coherence of oscillations in many neuropsychiatric conditions including Alzheimer's disease (AD). In the present paper, we examine sensory-evoked and event-related gamma coherences elicited by visual stimuli in three sub-gamma bands in two sub-groups of patients with AD (i.e., acetylcholinesterase-inhibitor treated and untreated) and healthy controls. METHODS: We studied a total of 39 patients with probable mild AD (according to NINCDS-ADRDA criteria) who had been sub-divided into untreated (n = 21) and treated (n = 18) (patients either on cholinergic monotherapy or combined therapy with memantine) AD groups, and 21 age-, gender-, and education-matched healthy elderly controls. A simple flash visual paradigm was applied for the acquisition of sensory-evoked coherences. Event-related coherences were elicited using a classical visual oddball paradigm. Both sensory-evoked and event-related gamma coherences were calculated for long-distance intrahemispheric pairs for three frequency ranges: 25-30 Hz, 30-35 Hz, and 40-48 Hz in post-stimulus 0-800 ms duration. The long-distance intrahemispheric pairs from both sides were fronto-parietal, fronto-temporal, fronto-temporoparietal, fronto-occipital, centro-occipital and parieto-occipital. RESULTS: The sensory-evoked or event-related gamma coherences revealed that both treated and untreated AD patients had significantly increased values compared to healthy controls in all three sub-gamma bands. Moreover, the treated AD patients demonstrated significantly higher fronto-parietal gamma coherences during both sensory stimulation and oddball paradigm and lower occipito-parietal coherences during oddball paradigm in comparison to untreated AD patients. CONCLUSION: The present study demonstrated that an increase of gamma coherences was present in response to both visual sensory and cognitive stimulation in AD patients in all gamma sub-bands. Therefore, gamma oscillatory activity seems to be fundamental in brain functions at both the sensory and cognitive levels. The increase of gamma coherence values was not due to cholinergic treatment to any significant extent, as both treated and untreated AD patients had increased gamma coherence values compared to healthy controls. The use of coherence values reflecting brain connectivity holds potential for neuroimaging of AD and understanding brain dynamics related to the effects of medication.

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.

Decrease of Delta Oscillatory Responses in Cognitively Normal Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. This study aims to compare sensory-evoked oscillations (SEOs) and event-related oscillations (EROs) of visual modality in cognitively normal PD patients and healthy controls. Sixteen PD and 16 age-, gender-, and education-matched healthy controls participated in the study. A simple flashlight was used for SEO and a classical visual oddball paradigm was used for target ERO. Oscillatory responses in the delta frequency range (0.5-3.5 Hz) were examined. Significantly lower delta ERO and SEO responses were found in PD patients than healthy controls. Delta ERO responses were decreased at all frontal, central and parietal locations, whereas delta SEO responses were decreased over mid and right central locations in PD. According to the notion that SEO reflects the activity of sensory networks and ERO reflects cognitive networks, these findings indicate that PD patients have impairments in both cognitive and sensory networks of visual modality. Decreased delta ERO responses indicate that the subliminal cognitive changes in PD can be detected by electrophysiological methods. These results demonstrate that brain oscillatory responses have the potential to be studied as a biomarker for visual cognitive and sensory networks in PD.

Links of Consciousness, Perception, and Memory by Means of Delta Oscillations of Brain.

The aim of this report is threefold: (1) First, we accomplish a survey integrating the description of consciousness, perception, and memory according to the views of descriptions of Hermann Helmholtz, Sigmund Freud, Henri Bergson, and Gustav Jung. (2) In the second step, we present experimental results for defining the machineries of sensation and perception: (a) electrical responses of isolated ganglion of Helix pomatia were measured upon odor stimuli that elicited varied degrees of responses. Such a model may give an idea of the control of sensation in the preconscious state of a living tissue. (b) We also describe experiments at the human hearing threshold level. (c) Further, the omission of working memory will be shown with the attenuation of delta response in Alzheimer's subjects in P300 measurements. (d) Finally, the measurement of auditory evoked potentials during slow-wave sleep in the cat brain explains the auditory responses that are not heard at this level of consciousness. (3) In the third step, we aim to provide a synopsis related to integration of perception, memory, and consciousness. By using concepts of important scientists as S. Freud on consciousness, we also tentatively discuss the boundaries of the transition of unconsciousness states to conscious states.

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 Alzheimer's 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 participant's 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 participant's 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.

Neurophysiological assessment of Alzheimer's disease individuals by a single electroencephalographic marker.

Here we presented a single electroencephalographic (EEG) marker for a neurophysiological assessment of Alzheimer's disease (AD) patients already diagnosed by current guidelines. The ability of the EEG marker to classify 127 AD individuals and 121 matched cognitively intact normal elderly (Nold) individuals was tested. Furthermore, its relationship to AD patients' cognitive status and structural brain integrity was examined. Low-resolution brain electromagnetic tomography (LORETA) freeware estimated cortical sources of resting state eyes-closed EEG rhythms. The EEG marker was defined as the ratio between the activity of parieto-occipital cortical sources of delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms. Results showed 77.2% of sensitivity in the recognition of the AD individuals; 65% of specificity in the recognition of the Nold individuals; and 0.75 of area under the receiver-operating characteristic curve. Compared to the AD subgroup with the EEG maker within one standard deviation of the Nold mean (EEG-), the AD subgroup with EEG+ showed lower global cognitive status, as revealed by Mini-Mental State Evaluation score, and more abnormal values of white-matter and cerebrospinal fluid normalized volumes, as revealed by structural magnetic resonance imaging. We posit that cognitive and functional status being equal, AD patients with EEG+ should receive special clinical attention due to a neurophysiological "frailty". EEG+ label can be also used in clinical trials (i) to form homogeneous groups of AD patients diagnosed by current guidelines and (ii) as end-point to evaluate intervention effects.

Increased Beta Frequency (15-30 Hz) Oscillatory Responses in Euthymic Bipolar Patients Under Lithium Monotherapy.

The effect of lithium on neurocognition is not still fully explored. Brain oscillatory activity is altered in bipolar disorder. We aimed to assess the oscillatory responses of euthymic bipolar patients and how they are affected by lithium monotherapy. Event-related oscillations in response to visual target stimulus during an oddball paradigm in 16 euthymic drug-free and 13 euthymic lithium-treated bipolar patients were compared with 16 healthy controls. The maximum peak-to-peak amplitudes were measured for each subject's averaged beta (15-30 Hz) responses in the 0- to 300-ms time window over frontal (F3, Fz, F4), central (C3, Cz, C4), temporal (T7, T8), temporo-parietal (TP7, TP8), parietal (P3, Pz, P4), and occipital (O1, Oz, O2) areas. Patients under lithium monotherapy had significantly higher beta responses to visual target stimuli than healthy controls (P=.017) and drug-free patients (P=.015). The increase in beta response was observed at all electrode locations, however, the difference was statistically significant for the left (T7; P=.016) and right (T8; P=.031) temporal beta responses. Increased beta responses in drug-free patients and further significant increase in lithium-treated patients may be indicative of a core pathophysiological process of bipolar disorder and how it is affected by lithium. Whether the finding corresponds to lithium's corrective effect on the underlying pathology or to its neurocognitive side effect remains to be further explored. In either case, the finding is a sign that the oscillatory activity may be useful in tracking medication effect in bipolar disorder.

The CLAIR model: Extension of Brodmann areas based on brain oscillations and connectivity.

Since the beginning of the last century, the localization of brain function has been represented by Brodmann areas, maps of the anatomic organization of the brain. They are used to broadly represent cortical structures with their given sensory-cognitive functions. In recent decades, the analysis of brain oscillations has become important in the correlation of brain functions. Moreover, spectral connectivity can provide further information on the dynamic connectivity between various structures. In addition, brain responses are dynamic in nature and structural localization is almost impossible, according to Luria (1966). Therefore, brain functions are very difficult to localize; hence, a combined analysis of oscillation and event-related coherences is required. In this study, a model termed as "CLAIR" is described to enrich and possibly replace the concept of the Brodmann areas. A CLAIR model with optimum function may take several years to develop, but this study sets out to lay its foundation.

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 Alzheimer's 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.

Review of evoked and event-related delta responses in the human brain.

In the last decade, the brain's oscillatory responses have invaded the literature. The studies on delta (0.5-3.5Hz) oscillatory responses in humans upon application of cognitive paradigms showed that delta oscillations are related to cognitive processes, mainly in decision making and attentional processes. The present manuscript comprehensively reviews the studies on delta oscillatory responses upon cognitive stimulation in healthy subjects and in different pathologies, namely Alzheimer's disease, Mild Cognitive Impairment (MCI), bipolar disorder, schizophrenia and alcoholism. Further delta oscillatory response upon presentation of faces, facial expressions, and affective pictures are reviewed. The relationship between pre-stimulus delta activity and post-stimulus evoked and event-related responses and/or oscillations is discussed. Cross-frequency couplings of delta oscillations with higher frequency windows are also included in the review. The conclusion of this review includes several important remarks, including that delta oscillatory responses are involved in cognitive and emotional processes. A decrease of delta oscillatory responses could be a general electrophysiological marker for cognitive dysfunction (Alzheimer's disease, MCI, bipolar disorder, schizophrenia and alcoholism). The pre-stimulus activity (phase or amplitude changes in delta activity) has an effect on post-stimulus EEG responses.