Human EEG gamma oscillations in neuropsychiatric disorders.

Due to their small amplitude, the importance of high-frequency EEG oscillations with respect to cognitive functions and disorders is often underestimated as compared to slower oscillations. This article reviews the literature on the alterations of gamma oscillations (about 30-80 Hz) during the course of neuropsychiatric disorders and relates them to a model for the functional role of these oscillations for memory matching. The synchronous firing of neurons in the gamma-band has been proposed to bind multiple features of an object, which are coded in a distributed manner in the brain, and is modulated by cognitive processes such as attention and memory. In certain neuropsychiatric disorders the gamma activity shows significant changes. In schizophrenic patients, negative symptoms correlate with a decrease of gamma responses, whereas a significant increase in gamma amplitudes is observed during positive symptoms such as hallucinations. A reduction is also observed in Alzheimer's Disease (AD), whereas an increase is found in epileptic patients, probably reflecting both cortical excitation and perceptual distortions such as déjà vu phenomena frequently observed in epilepsy. ADHD patients also exhibit increased gamma amplitudes. A hypothesis of a gamma axis of these disorders mainly based on the significance of gamma oscillations for memory matching is formulated.

A model for P300 generation based on responses to near-threshold visual stimuli.

Near-threshold and suprathreshold visual ERPs and their frequency components were compared with the aim to obtain further information on the generation mechanism of the P300 wave. Decrease of the stimulus energy from suprathreshold to near-threshold level resulted in an increase of the P300 amplitude specifically in the occipital region. This finding was in contrast with the P300 amplitude decrease in central and frontal regions and its constancy in parietal area. Delta and theta responses showed a similar distribution pattern, whereas alpha responses decreased in all regions as the stimulus energy decreased. We conclude that P300 wave may correspond to a delta oscillation during a widespread, transient interruption of afferent inputs from subcortical structures to the cortical neurons including those in the visual sensory area and simultaneous increase of the cortico-cortical interactions. If visual inputs are of suprathreshold strength, they override this effect specifically in the primary visual area and disrupt the cortico-cortical interactions and the emergence of P300 in the occipital cortex.

The effects of subthreshold visual stimulation on P300 response.

The effects of the subthreshold visual stimuli on the electrical activity of the brain were investigated by an oddball-like paradigm and a single-stimulus paradigm. In the oddball-like paradigm, suprathreshold and subthreshold stimuli were presented randomly where the suprathreshold stimulus probability was 0.24. The single-stimulus paradigm contained only the suprathreshold stimuli and was identical to the oddball-like paradigm apart from the absence of subthreshold stimuli. Suprathreshold P3b amplitude was larger for the oddball-like than for the single-stimulus condition particularly in the centro-parietal region. This result suggests that at least one component of the P300 wave could be assigned to an automatic comparison and memory updating process which runs unconsciously.

The phase-locking of auditory gamma band responses in humans is sensitive to task processing.

The present study assessed the effects of stimulus task-relevance and certainty on early and late 40 Hz (gamma) band responses (GBRs) in humans. Auditory GBRs of nine young adults were recorded in passive listening, simple reaction task, and choice-reaction task (target probability = 0.5) conditions and evaluated in three consecutive post-stimulus periods (0-120, 120-250, 250-400 ms) corresponding to the serial occurrence of gamma oscillation bursts. Amplitude and phase-locking of GBRs within these bursts were analysed separately at the level of single sweeps by applying a method that allows the independent quantification of between-sweep synchronization. Major results showed that the effects of stimulus certainty and task relevance on single response amplitude were specific and different from the effects on the phase-locking. The functional involvement of the early and late auditory gamma responses was distinct: early auditory gamma band responses appear primarily associated with focused attention, while the late gamma responses vary with motor-task relevance. It is concluded that along with power measures, the stability of phase-locking of gamma band responses should be regarded as a functionally meaningful parameter that varies with processing demands and recording site.

Time-frequency analysis reveals multiple functional components during oddball P300.

A time-frequency decomposition was applied to rare target and frequent non-target event-related potentials (ERPs) elicited in an oddball condition to assess whether multiple functional components occur in the P300 latency range. The wavelet transform (WT) was used because it allows capture of simultaneous or partly overlapping components in ERPs without loosing their temporal relationships. The application of a four-octave quadratic B-spline wavelet transform at the level of single-sweep data allowed us to obtain new information and revealed the presence of separate events during P300 development. Several delta, theta, and alpha frequency components in the P300 latency range differed between target and non-target processing. These findings indicate that P300 is composed of multiple functional components and that the WT method is of use for the study of P300 functional correlates more precisely.

Multiple time-frequency components account for the complex functional reactivity of P300.

Consecutive and overlapping time-frequency (TF) components of auditory event-related brain potentials (ERPs) were analyzed to examine whether multiple co-existing components may account for the complex functional reactivity of P300. Auditory ERPs of 14 adult subjects were decomposed by means of the wavelet transform (WT), and TF components within P300 were tested in a systematic manner for the effects of major P300 determinants: stimulus probability, active discrimination, and mental count task. The results demonstrated that several partly or fully simultaneous delta, theta, and alpha TF components significantly depend on the factors eliciting P300, and also manifest distinct patterns of task reactivity and scalp distribution. Thus, specific functional processes that underlie the P300 ERP can be distinguished that help to account for its responsiveness to task variables.

Slow cortical potential shifts modulate the sensory threshold in human visual system.

The relationship between the spontaneous slow cortical potential shifts and the detection of visual stimuli at sensory threshold were investigated. The mean slow cortical potentials preceding the detected stimuli were more negative than those preceding the missed stimuli. Accordingly, the stimulus detection performance was higher during negative compared to positive cortical potential shifts. These findings demonstrate that the cortical negativity reflects increased excitability of neural networks, thereby facilitates the detection of threshold stimuli, in contrast to cortical positivity. Therefore, at near-threshold stimulus intensities one reason for detecting the stimulus in one trial but missing it in another could be the change in the EEG baseline between the trials.

Electroencephalogram alpha (8-15 Hz) responses to visual stimuli in cat cortex, thalamus, and hippocampus: a distributed alpha network?

To investigate possible functional correlates of alpha (8-15 Hz) oscillations in the electroencephalogram (EEG) intracranial recordings in cats (from thalamus, occipital cortex, and hippocampus) were performed. In response to visual stimuli, event-related alpha oscillations were observed. Such alpha responses were found not only in a specific sensory (visual) pathway but also in the hippocampus, hinting at a possible distributed alpha response system.

Music effects on event-related potentials of humans on the basis of cultural environment.

Auditory oddball responses were recorded from Turkish subjects in a silent environment or superimposed on white noise, or music played with violoncello or a similar music played with ney, a reed flute frequently listened by the Turkish population. P3 amplitudes with ney music in the background were significantly larger than both the white noise and violoncello backgrounds. The topography of the P3 response changed significantly between the ney and silent background conditions, indicating a relatively higher participation of frontal areas during hearing ney. Our results showed that hearing music of a familiar style increases the allocation of attentional resources during memory updating processes which is supposed to determine the P3 amplitude, and therefore showed the effects of cultural environment on the cognitive processes.

Slow cortical potential shifts modulate P300 amplitude and topography in humans.

Effects of the spontaneous slow cortical potential (SCP) shifts of the electroencephalogram (EEG) on the P300 response were investigated on ten healthy volunteers. P300 responses were recorded using an auditory oddball paradigm, where target stimuli were presented regularly after every four standard stimuli. Single event-related potential (ERP) sweeps exhibiting negative or positive SCP shifts were averaged separately. The P300 amplitude was significantly larger during negative SCP shifts. Furthermore, the topographies of P200 and P300 waves obtained during negative and positive SCP shifts showed significant differences. The results indicate that the SCP shifts in single ERP sweeps, which are considered to be correlated with the arousal or basic activity level of the cortex, explain at least part of the inter-trial variability of P300 response.

Theta rhythmicities following expected visual and auditory targets.

Evoked (EPs) as well as event-related potentials (ERPs) were recorded from two groups of 10 healthy, voluntary subjects in auditory and visual modalities. For ERP recordings 'the omitted stimulus paradigm' was employed, in which the subjects were expected to mark mentally the onset time (time prediction task) of the omitted stimulus (target). The standard auditory (AEP) and visual (VEP) evoked potentials and auditory and visual ERPs to the preceding stimuli of the omitted ones were analyzed in time and frequency domains. In the time domain the time prediction task induced increases of the amplitudes of waves existing in standard EPs; however, an additional wave or component could not be detected. Analysis of amplitude frequency characteristics (AFCs) revealed, however, selective, significant increases of the theta (3-6 Hz) frequency components of the responses concerned. These theta increases were especially evident in the frontal and parietal recording sites. Our findings suggest an association between the theta frequency components of transient evoked responses, the association areas of the brain and cognitive performance. The neurophysiological basis of scalp recorded ERPs are discussed in relation to the findings of animal studies with EEG and single unit recordings from cortical and subcortical structures.

Event-related theta oscillations: an integrative and comparative approach in the human and animal brain.

This report provides a synthesis of results in both cat and human brains in order to point out the importance of theta responses during cognitive processes and P300 paradigms. The unique features of this report consisted of the fact that human and cat data during several cognitive paradigms were compared. The results open the way to formulate the selectively distributed theta system in the brain as analyzed by Basar, Schürmann and Sakowitz (this issue).

P300-response: possible psychophysiological correlates in delta and theta frequency channels. A review.

The present paper combines a review of event-related potentials (ERPs) with empirical data concerning the question: what are the differences between auditory evoked potentials (EPs) and two types of ERPs with respect to their frequency components? In this study auditory EPs were elicited by 1500 Hz tones. The first type of ERPs was responses to 3rd attended tones in an omitted stimulus paradigm where every 4th stimulus was omitted. The second type of ERPs was responses to rare 1600 Hz tones in an oddball paradigm. The amplitudes of delta and theta components of EPs and ERPs showed significant differences: in responses to 3rd attended tones there was a significant increase in the theta frequency band (frontal and parietal locations; 0-250 ms). In the delta frequency band there was no significant change. In contrast a diffuse delta increase occurred in oddball responses and an additional prolongation of theta oscillations was observed (late theta response: 250-500 ms). These results are discussed in the context of ERPs as induced rhythmicities. The intracranial sources of ERPs, their psychological correlates and the role of theta rhythms in the cortico-hippocampal interaction are reviewed. From these results and from the literature a working hypothesis is derived assuming that delta responses are mainly involved in signal matching, decision making and surprise, whereas theta responses are more related to focused attention and signal detection.

Event-related theta rhythms in cat hippocampus and prefrontal cortex during an omitted stimulus paradigm.

In a recent study on human subjects which performed a time prediction task in an omitted stimulus paradigm we found an increase in the amplitudes of evoked potentials (EPs) for the stimulus preceding the omitted stimuli, probably due to expectancy and focused attention. The amplitude increases were dominant over frontal and parietal association areas and were mainly reflected in enhancements of the theta (3-6 Hz) components. In the present study we analyse the responses of the auditory cortex (GEA, gyrus ectosylvianus anterior), different parts of hippocampus (CA1, CA3), reticular formation (RF), and motor cortex (MC) of the cat brain using a similar paradigm. Similar theta component increases of the EPs were obtained in various parts of the hippocampus, which were dominant in pyramidal cell layers (CA3, CA4), and in motor cortex. The results are interpreted as signs of a diffuse theta response system in the brain including mainly the hippocampus and frontal and parietal association areas. The diffuse theta system is probably involved in general attention and expectancy processes.

Event-related oscillations are 'real brain responses'--wavelet analysis and new strategies.

The EEG consists of the activity of an ensemble of generators producing rhythmic activity in several frequency ranges. These oscillators are active usually in a random way. However, by application of sensory stimulation these generators are coupled and act together in a coherent way. This synchronization and enhancement of EEG activity gives rise to 'evoked' or 'event-related oscillations'. The compound evoked potential manifests as superimposition of evoked rhythms in the EEG frequencies ranging from delta to gamma ('natural frequencies of the brain'). The superimposition principle is described with efficient strategies and by utilization of an efficient algorithm. The wavelet analysis confirms the results of the combined analysis procedure obtained by using the amplitude frequency characteristics (AFCs) and digital filtering. The AFC and adapted digital filtering methods are based on the first approach to analyze average evoked potentials. In contrast, the wavelet analysis is based on signal retrieval and selection among a large number of sweeps recorded in a given physiological or psychological experiment. By combining all these results and concepts, it can be stated that the wavelet analysis underlines and extends the expression that alpha-, theta-, delta-, and gamma-responses described in this report are the most important brain responses related to psychophysiological functions. The wavelet analysis confirms once more the expression 'real signals' which we attribute to EEG frequency responses of the brain. It will be demonstrated that the delta, theta, and alpha responses (i.e. the rhythms 'predicted' by digital filtering) are real brain oscillations. The frequency components of the event-related potential vary independently of each other with respect to: (a) their relation to the event; (b) their topographic distribution; and (c) with the mode of the physiological measurements.

Selectively distributed gamma band system of the brain.

Experiments from the cat brain demonstrate that gamma responses can be recorded in cortex, hippocampus, cerebellum, formatio reticularis and thalamus, independent of the mode of sensory stimulation. These results support the hypothesis of a selectively distributed gamma system of the brain.

Topological distribution of oddball 'P300' responses.

This report describes the frequency response of the oddball paradigm upon auditory stimuli. Other reports related to wavelet analysis of the same ERPs (Demiralp et al., 1999) and the application of visual signals (Schürmann et al., this volume) indicate that the P300 response has a dominant delta response oscillation, independent of the modality of the stimulation. Moreover, the adaptive digital filtering and the wavelet analysis lead to very similar results, confirming that delta responses are real brain responses as already mentioned, by Basar et al. (this volume). The theta response has a second late response window in comparison to auditory evoked potentials. Moreover, the functional significance of the selectively distributed theta and delta systems of the brain will be clearly demonstrated. Signal detection, short-term memory, and decision-making processes are discussed.

Wavelet analysis of oddball P300.

The comparative wavelet analysis presented in details by Demiralp et al. (1999), Ademoglu (1995) and by Basar et al. (2001) will be now applied to oddball P300 results (see Basar-Eroglu et al., 2001). The results obtained basically confirm those obtained by using adaptive digital filtering: The delta response dominates the P300 potential while the theta response is prolonged in a second late window.

Decomposition of event-related brain potentials into multiple functional components using wavelet transform.

Event related brain potential (ERP) waveforms consist of several components extending in time, frequency and topographical space. Therefore, an efficient processing of data which involves the time, frequency and space features of the signal, may facilitate understanding the plausible connections among the functions, the anatomical structures and neurophysiological mechanisms of the brain. Wavelet transform (WT) is a powerful signal processing tool for extracting the ERP components occurring at different time and frequency spots. A technical explanation of WT in ERP processing and its four distinct applications are presented here. The first two applications aim to identify and localize the functional oddball ERP components in terms of certain wavelet coefficients in delta, theta and alpha bands in a topographical recording. The third application performs a similar characterization that involves a three stimulus paradigm. The fourth application is a single sweep ERP processing to detect the P300 in single trials. The last case is an extension of ERP component identification by combining the WT with a source localization technique. The aim is to localize the time-frequency components in three dimensional brain structure instead of the scalp surface. The time-frequency analysis using WT helps isolate and describe sequential and/or overlapping functional processes during ERP generation, and provides a possibility for studying these cognitive processes and following their dynamics in single trials during an experimental session.

Detection of P300 waves in single trials by the wavelet transform (WT).

The P300 response is conventionally obtained by averaging the responses to the task-relevant (target) stimuli of the oddball paradigm. However, it is well known that cognitive ERP components show a high variability due to changes of cognitive state during an experimental session. With simple tasks such changes may not be demonstrable by the conventional method of averaging the sweeps chosen according to task-relevance. Therefore, the present work employed a response-based classification procedure to choose the trials containing the P300 component from the whole set of sweeps of an auditory oddball paradigm. For this purpose, the most significant response property reflecting the P300 wave was identified by using the wavelet transform (WT). The application of a 5 octave quadratic B-spline-WT on single sweeps yielded discrete coefficients in each octave with an appropriate time resolution for each frequency range. The main feature indicating a P300 response was the positivity of the 4th delta (0.5-4 Hz) coefficient (310-430 ms) after stimulus onset. The average of selected single sweeps from the whole set of data according to this criterion yielded more enhanced P300 waves compared with the average of the target responses, and the average of the remaining sweeps showed a significantly smaller positivity in the P300 latency range compared with the average of the non-target responses. The combination of sweeps classified according to the task-based and response-based criteria differed significantly. This suggests an influence of changes in cognitive state on the presence of the P300 wave which cannot be assessed by task performance alone.