Multistable perception elicits compensatory alpha activity in older adults.

Multistable stimuli lead to the perception of two or more alternative perceptual experiences that spontaneously reverse from one to the other. This property allows researchers to study perceptual processes that endogenously generate and integrate perceptual information. These endogenous processes appear to be slowed down around the age of 55 where participants report significantly lower perceptual reversals. This study aimed to identify neural correlates of this aging effect during multistable perception utilizing a multistable version of the stroboscopic alternative motion paradigm (SAM: endogenous task) and a control condition (exogenous task). Specifically, age-related differences in perceptual destabilization and maintenance processes were examined through alpha responses. Electroencephalography (EEG) of 12 older and 12 young adults were recorded during SAM and control tasks. Alpha band activity (8-14 Hz) was obtained by wavelet-transformation of the EEG signal and analyzed for each experimental condition. Endogenous reversals induced gradual decrease in posterior alpha activity in young adults which is a replication of previous studies' findings. Alpha desynchronization was shifted to anterior areas and prevalent across the cortex except the occipital area for older adults. Alpha responses did not differ between the groups in the control condition. These findings point to recruitment of compensatory alpha networks for maintenance of endogenously generated percepts. Increased number of networks responsible for maintenance might have extended the neural satiation duration and led to decreased reversal rates in older adults.

Aging attenuated theta response during multistable perception.

Multistable stimuli are physically unchanging, but elicit spontaneous perceptual reversals between multiple internally generated perceptual alternatives. Perceptual reversal rates seem to decrease in older adults; however, there is no literature on the electrophysiological correlates of this performance decrease. Here, we aimed to identify age-related changes in theta activity that relate to decreased reversal rates of older adults. Electroencephalography (EEG) of young (n = 15) and older adults (n = 15) was recorded during presentation of stroboscopic alternative motion (SAM) and a control stimulus. Time-frequency amplitudes were extracted in 4-8 Hz via Morlet wavelet convolution. Older adults had lower SAM reversals as well as decreased accuracy, increased reaction time (RT) and increased RT variability in the control task. In older adults, reversal-related frontal theta response was diminished, yet parietal theta was intact. In the parietal area, the relationship between theta response and reversal rates was robust, but in the frontal area, was dependent on age-related variance. Result indicated that, in older adults, top-down facilitation of perceptual reversals was impaired. This appears to result in a predominantly bottom-up resolution of perceptual multistability. Age-related degradation of sensory areas in this bottom-up-driven resolution process might have slowed reversals. This study presents the first electrophysiological correlates of age-related impairment in multistable perceptual integration.

Treatment effects on event-related EEG potentials and oscillations in Alzheimer's disease.

Alzheimer's disease dementia (ADD) is the most diffuse neurodegenerative disorder belonging to mild cognitive impairment (MCI) and dementia in old persons. This disease is provoked by an abnormal accumulation of amyloid-beta and tauopathy proteins in the brain. Very recently, the first disease-modifying drug has been licensed with reserve (i.e., Aducanumab). Therefore, there is a need to identify and use biomarkers probing the neurophysiological underpinnings of human cognitive functions to test the clinical efficacy of that drug. In this regard, event-related electroencephalographic potentials (ERPs) and oscillations (EROs) are promising candidates. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer's Association and Global Brain Consortium reviewed the field literature on the effects of the most used symptomatic drug against ADD (i.e., Acetylcholinesterase inhibitors) on ERPs and EROs in ADD patients with MCI and dementia at the group level. The most convincing results were found in ADD patients. In those patients, Acetylcholinesterase inhibitors partially normalized ERP P300 peak latency and amplitude in oddball paradigms using visual stimuli. In these same paradigms, those drugs partially normalize ERO phase-locking at the theta band (4-7 Hz) and spectral coherence between electrode pairs at the gamma (around 40 Hz) band. These results are of great interest and may motivate multicentric, double-blind, randomized, and placebo-controlled clinical trials in MCI and ADD patients for final cross-validation.

Evoked and induced EEG oscillations to visual targets reveal a differential pattern of change along the spectrum of cognitive decline in Alzheimer's Disease.

In recent years, quantitative variables derived from the electroencephalogram (EEG) attract an increasing interest for the evaluation of neurodegenerative diseases, as EEG registers the neuro-electric activity with a high temporal resolution and provides a cost-effective and easily accessible, non-invasive method. Event-related oscillations (EROs) as oscillatory responses in the EEG to specific events further provide the possibility to track the cognitive decline in a task-specific manner. Current study in search for potential ERO biomarkers to distinguish different stages of cognitive decline along the Alzheimer's Disease (AD) continuum re-analyzed a combined set of data collected and analyzed in previous studies by Basar and coworkers. Target responses of a visual oddball experiment recorded from 33 AD patients, 46 Mild Cognitive Impairment (MCI) patients and 48 age, gender, and education matched normal elderly controls were analyzed for both evoked (phase-locked) and total (phase-locked + non-phase-locked) ERO powers in delta, theta, alpha, beta and gamma bands by applying continuous wavelet transform (WT) on averaged and single trial data, respectively. The cluster-based nonparametric permutation test implemented in the FieldTrip toolbox revealed significant differences among the three groups. While the total delta and theta responses already significantly declined in the MCI stage with further spatial expansion of the decline in AD, the evoked delta response reached a statistically significant reduction level in the AD stage. We obtained no significant difference among groups for alpha, beta and gamma frequency bands. These results suggest that total delta and theta EROs to oddball targets may be useful for early detection of the disease in MCI stage, while the evoked delta response allows detecting the conversion to AD.

Altered gamma and theta oscillations during multistable perception in schizophrenia.

OBJECTIVE: Coherent object perception in patients with schizophrenia is known to be impaired. Oscillatory brain dynamics constitute a fundamental mechanism for the coordinated communication of neural circuits. Such dynamics have been proposed to reflect impaired spatio-temporal integration of sensory and cognitive processes during object perception in schizophrenia. METHOD: EEG recordings of patients with schizophrenia (n = 23) and control participants (n = 23) were examined. Presented were either an ambiguous (multistable) stimulus, endogenously inducing switching between two perceptual alternatives, or a slightly modified unambiguous control stimulus, during which perceptual reversals were triggered by a minor change in the stimulus configuration. Event-related amplitude modulation induced by perceptual reversals was analyzed for theta (3-8 Hz) and gamma band oscillations (28-48 Hz). RESULTS: Patients displayed increased reaction times and more errors when indicating unambiguous reversals. The patients´ amplitude enhancement of theta oscillations was diminished in both task conditions. During the control task were gamma amplitudes larger in patients than in healthy participants. CONCLUSION: The results indicate that impairments in generating coherent percepts are reflected in alterations of multiple frequency bands and time windows. Changes in gamma band oscillations may reflect the patients' impairments in perceptuo-cognitive integration processes. Diminished theta amplitude modulation in patients further emphasize diminished top-down cognitive control during perceptual reversals. SIGNIFICANCE: This study provides insight into how theta and gamma oscillations underlie changes in object perception, and thereby possibly the generation of core symptoms, in schizophrenia. This paper is dedicated to Prof. Dr. Erol Basar, a pioneer in research on oscillatory braindynamics. He was tireless in his effort to understand brain functions and integratedphilosophy, physics, biology and psychology in his research. His vision on how informationis coded in brain networks inspired many researchers in the last 40 years. With him, we not only lose an exceptional researcher, but also a supportive academic teacher and mentor with a persistent, prolific enthusiasm for international and collaborative projects.

Measurement of cognitive dynamics during video watching through event-related potentials (ERPs) and oscillations (EROs).

Event-related potentials (ERPs) and oscillations (EROs) are reliable measures of cognition, but they require time-locked electroencephalographic (EEG) data to repetitive triggers that are not available in continuous sensory input streams. However, such real-life-like stimulation by videos or virtual-reality environments may serve as powerful means of creating specific cognitive or affective states and help to investigate dysfunctions in psychiatric and neurological disorders more efficiently. This study aims to develop a method to generate ERPs and EROs during watching videos. Repeated luminance changes were introduced on short video segments, while EEGs of 10 subjects were recorded. The ERP/EROs time-locked to these distortions were analyzed in time and time-frequency domains and tested for their cognitive significance through a long term memory test that included frames from the watched videos. For each subject, ERPs and EROs corresponding to video segments of recalled images with 25% shortest and 25% longest reaction times were compared. ERPs produced by transient luminance changes displayed statistically significant fluctuations both in time and time-frequency domains. Statistical analyses showed that a positivity around 450 ms, a negativity around 500 ms and delta and theta EROs correlated with memory performance. Few studies mixed video streams with simultaneous ERP/ERO experiments with discrete task-relevant or passively presented auditory or somatosensory stimuli, while the present study, by obtaining ERPs and EROs to task-irrelevant events in the same sensory modality as that of the continuous sensory input, produces minimal interference with the main focus of attention on the video stream.

Novelty N2-P3a Complex and Theta Oscillations Reflect Improving Neural Coordination Within Frontal Brain Networks During Adolescence.

Adolescents are easily distracted by novel items than adults. Maturation of the frontal cortex and its integration into widely distributed brain networks may result in diminishing distractibility with the transition into young adulthood. The aim of this study was to investigate maturational changes of brain activity during novelty processing. We hypothesized that during adolescence, timing and task-relevant modulation of frontal cortex network activity elicited by novelty processing improves, concurrently with increasing cognitive control abilities. A visual novelty oddball task was utilized in combination with EEG measurements to investigate brain maturation between 8-28 years of age (n = 84). Developmental changes of the frontal N2-P3a complex and concurrent theta oscillations (4-7 Hz) elicited by rare and unexpected novel stimuli were analyzed using regression models. N2 amplitude decreased, P3a amplitude increased, and latency of both components decreased with age. Pre-stimulus amplitude of theta oscillations decreased, while inter-trial consistency, task-related amplitude modulation and inter-site connectivity of frontal theta oscillations increased with age. Targets, intertwined in a stimulus train with regular non-targets and novels, were detected faster with increasing age. These results indicate that neural processing of novel stimuli became faster and the neural activation pattern more precise in timing and amplitude modulation. Better inter-site connectivity further implicates that frontal brain maturation leads to global neural reorganization and better integration of frontal brain activity within widely distributed brain networks. Faster target detection indicated that these maturational changes in neural activation during novelty processing may result in diminished distractibility and increased cognitive control to pursue the task.

Aging differentially affects alpha and beta sensorimotor rhythms in a go/nogo task.

OBJECTIVES: This study compared sensorimotor alpha and beta brain oscillations in young and older adults, to examine their functional distinctness and susceptibility to aging. METHODS: Electroencephalographic data were compared between young (age 23±3) and older adults (age 64±7) in terms of event-related spectral perturbation in alpha and beta bands during a go/nogo task. RESULTS: Age selectively influenced beta rhythms, with younger compared to older adults showing, first, less attenuation during movement preparation and execution, and, second, a greater rebound after movement end. Alpha rhythms differed after response inhibition, with an additional alpha rebound occurring in older, but not younger adults. CONCLUSION: The results indicate neural over-recruitment in healthy aging, which appears most likely linked to alterations in multiple factors associated with sensory and cognitive aspects of motor control, and which does not consistently or directly impact response speed. SIGNIFICANCE: The results imply that sensorimotor alpha and beta rhythms may reflect different neural trajectories in aging.

Maturation of the P3 and concurrent oscillatory processes during adolescence.

OBJECTIVE: During adolescence event-related modulations of the neural response may increase. For slow event-related components, such as the P3, this developmental change may be masked due to increased amplitude levels of ongoing delta and theta oscillations in adolescents. METHODS: In a cross-sectional study design, EEG was measured in 51 participants between 13 and 24years. A visual oddball paradigm was used to elicit the P3. Our analysis focused on fronto-parietal activations within the P3 time-window and the concurrent time-frequency characteristics in the delta (∼0.5-4Hz) and theta (∼4-7Hz) band. RESULTS: The parietal P3 amplitude was similar across the investigated age range, while the amplitude at frontal regions increased with age. The pre-stimulus amplitudes of delta and theta oscillations declined with age, while post-stimulus amplitude enhancement and inter-trial phase coherence increased. These changes affected fronto-parietal electrode sites. CONCLUSIONS: The parietal P3 maximum seemed comparable for adolescents and young adults. Detailed analysis revealed that within the P3 time-window brain maturation during adolescence may lead to reduced spontaneous slow-wave oscillations, increased amplitude modulation and time precision of event-related oscillations, and altered P3 scalp topography. SIGNIFICANCE: Time-frequency analyses may help to distinguish selective neurodevelopmental changes within the P3 time window.

Altered alpha brain oscillations during multistable perception in schizophrenia.

Schizophrenia is a complex mental disorder with impairments in integrating sensory and cognitive functions, leading to severe problems in coherent perception. This impairment might be accelerated during multistable perception. Multistable perception is a phenomenon, where a visual pattern gives rise to at least two different perceptual representations. We addressed this issue by assessing event-related alpha oscillations during continuous viewing of an ambiguous and unambiguous control stimulus. Perceptual reversals were indicated by a manual response, allowing differentiation between phases of reversion and non-reversion (that is perceptual stability) in both tasks. During the ambiguous task, patients and controls showed a comparable number of perceptual reversals. Alpha amplitudes in patients were larger in non-reversion phases, accompanied by a stronger decrease of alpha activity preceding the perceptual reversal. This group difference was pronounced for lower alpha activity and not apparent during the unambiguous task. This indicates that ambiguous perception taps into the specific deficits that patients experience in maintaining coherent perception. Given that top-down influences in generating a meaningful percept seems to be low in patients, they appear more dependent on sensory information. Similar, bottom-up mechanisms might be more important in triggering perceptual reversals in patients than in controls.

Multistable perception in children: Prefrontal delta oscillations in the developing brain.

The prefrontal cortex (PFC) is considered to be the primary source of attentional control during elementary visual processing as exemplified in perceptual ambiguity. Assuming that multistable perception activates a fronto-parietal network, we contrast the results of mature and developing cognitive systems to deduce the developmental status of underlying structures from behavioral performances and functional EEG parameters. We analyzed the topographical distribution, amplitude characteristics and inter-trial variability of a reversal-related delta response that accompanies perceptual switches between the two alternative percepts of an ambiguous motion pattern. Fourteen ten-year old children and an adult control group indicated changes of perceived motion directions by a button-press. EEG was recorded from frontal, central, parietal, and occipital locations of both hemispheres. Behavioral data shows a considerably lower reversal rate within the children sample, suggesting that the related mechanisms are not yet operating on an adult level. In contrast to findings in adults, the involved delta component emerges as part of an unspecific posterior activation, suggesting that a cortical specialization process has not been accomplished yet. On frontal locations the ten-year old children fail to yield a stable component. The synchronized fronto-parietal activity in adults may constitute the result of a specialization process that determined connection patterns and functionally tuned the involved areas. This implies a deficit in timing and temporal sequencing of neuronal activity in children, mainly attributable to a less functional differentiated PFC that has not been fully integrated yet into the cognitive ensemble.

Best method for analysis of brain oscillations in healthy subjects and neuropsychiatric diseases.

The research related to brain oscillations and their connectivity is in a new take-off trend including the applications in neuropsychiatric diseases. What is the best strategy to learn about functional correlation of oscillations? In this report, we emphasize combined application of several analytical methods as power spectra, adaptive filtering of Event Related Potentials, inter-trial coherence and spatial coherence. These combined analysis procedure gives the most profound approach to understanding of EEG responses. Examples from healthy subjects, Alzheimer's Diseases, schizophrenia, and Bipolar Disorder are described.

Theta response in schizophrenia is indifferent to perceptual illusion.

OBJECTIVE: Patients with schizophrenia are impaired in maintaining coherent perceptual experiences. This is reflected in the oscillatory theta response and can be investigated by visual illusions. Ambiguous stimuli elicit illusory perceptual switches while the stimulus remains unchanged. METHODS: Theta responses elicited by an ambiguous and unambiguous control stimulus were measured using the EEG during time periods of perceptual switching and perceptual stability (non-switching). RESULTS: For the ambiguous task, theta activity increased during perceptual switching in healthy controls only. For the unambiguous task, the switching-related increase of theta activity was larger in controls than in patients. This reduced modulation of the theta response seems not to be related to a general decrease of theta activity in patients. CONCLUSIONS: These findings may be related to disturbances in the spatio-temporal integration of neural activity in patients. Reporting ambiguous and unambiguous perceptual switches seems to be more demanding for patients with schizophrenia than healthy controls. SIGNIFICANCE: This is one of the first studies on the neurophysiologic correlates of illusory perception in schizophrenia. Focussing on the relation between different brain states (such as switching and non-switching) might integrate different findings about altered theta oscillations in schizophrenia.

Frontal theta activity is pronounced during illusory perception.

Object perception is driven by sensory information as well as expectations and prior experiences. The latter influence may increase when the sensory information is poor or inconclusive. Visual illusions, for example induced by ambiguous stimuli, provide a tool to investigate perceptual uncertainty, because ambiguous stimuli elicit switching between at least two perceptual alternatives. Theta oscillations may reflect the impact of visual illusion on perception since they are specifically important to coordinate information in large-scale brain networks, including visual sensory as well as higher-order brain areas. Theta responses elicited by an ambiguous and an unambiguous apparent motion-inducing stimulus were compared, thereby differentiating time periods of perceptual switching and perceptual stability (non-switching). The theta responses were larger at anterior than at posterior sites. This gradient was stronger during the ambiguous task than during the unambiguous task, even though sensory stimulation was comparable for both tasks. A transient increase of the theta response occurred during switching time periods for both the ambiguous and the unambiguous tasks, indicating that the theta response related to the perceptual switch might not be affected by the ambiguity of the stimulus. Irrespective of the percept switching or not, ambiguous stimuli elicited an enduring more prominent activation of higher-order rather than visual sensory brain areas. This indicates an increased reliance on expectations and prior information to ensure coherent object perception in particular when the visual information is degraded or elicits an ongoing conflict between perceptual interpretations.

Brain's alpha, beta, gamma, delta, and theta oscillations in neuropsychiatric diseases: proposal for biomarker strategies.

Brain oscillations have gained tremendous importance in neuroscience during recent decades as functional building blocks of sensory-cognitive processes. Research also shows that event-related oscillations (EROs) in "alpha," "beta," "gamma," "delta," and "theta" frequency windows are highly modified in pathological brains, especially in patients with cognitive impairment. The strategies and methods applied in the present report reflect the innate organization of the brain: "the whole brain work." The present paper is an account of methods such as evoked/event-related spectra, evoked/ERDs, coherence analysis, and phase-locking. The report does not aim to cover all strategies related to the systems theory applied in brain research literature. However, the essential methods and concepts are applied in several examples from Alzheimer's disease (AD), schizophrenia, and bipolar disorder (BD), and such examples lead to fundamental statements in the search for neurophysiological biomarkers in cognitive impairment. An overview of the results clearly demonstrates that it is obligatory to apply the method of oscillations in multiple electroencephalogram frequency windows in search of functional biomarkers and to detect the effects of drug applications. Again, according to the summary of results in AD patients and BD patients, multiple oscillations and selectively distributed recordings must be analyzed and should include multiple locations. Selective connectivity between selectively distributed neural networks has to be computed by means of spatial coherence. Therefore, by designing a strategy for diagnostics, the differential diagnostics, and application of (preventive) drugs, neurophysiological information should be analyzed within a framework including multiple methods and multiple frequency bands. The application of drugs/neurotransmitters gains a new impact with the analysis of oscillations and coherences. A more clear and differentiated analysis of drug effects can be attained in comparison to the application of the conventional wide-band evoked potential and event-related potential applications.

Auditory-evoked alpha oscillations imply reduced anterior and increased posterior amplitudes in schizophrenia.

OBJECTIVE: Most of the work on disturbed oscillatory activity during auditory tasks in schizophrenia has focused on reduced gamma oscillations at fronto-central sites. Recent studies of our group, however, indicate a more general disturbance affecting the spatial distribution of oscillatory brain activity of gamma as well as slow frequencies, such as alpha oscillations. METHODS: During a passive auditory listening task, electroencephalography was recorded from healthy controls and patients with schizophrenia. Stimulus-locked alpha activity within the first 250 ms after stimulus onset was analyzed from midline electrodes. RESULTS: Healthy controls showed the common fronto-central maximum of the early alpha response, while patients with schizophrenia showed lower fronto-central and larger parieto-occipital alpha activity than controls, leading to a more similar amplitude distribution across the midline electrode sites. CONCLUSIONS: The present results indicate malfunctioning long-range inhibition of task-irrelevant cortical areas in schizophrenia, which may disturb functional integration of perception and attention. We emphasize the importance of the whole-brain network theory for the understanding of schizophrenia since it proposes that integrative brain function is based on the coexistence and cooperative action of many interwoven and interacting sub-mechanisms. SIGNIFICANCE: Neuropsychiatric illnesses such as schizophrenia are marked by communication and coordination failures between different brain regions and different frequency bands.

Age-related increases in within-person variability: delta and theta oscillations indicate that the elderly are not always old.

Behavioral and electrophysiological data related to performance in an auditory Go/NoGo task were analyzed in young and older adults in the present study. Especially, differences in within-person variability in behavior and neural activity between young and older adults and changes in topography of slow event-related oscillations (EROs) were of interest. Within-person variability in behavior was assessed by reaction time (RT) variability. Event-related delta and theta oscillations were analyzed using time-frequency transformation, which can give information on the time-course of single trial event-related EEG spectral power enhancement and intertrial phase-locking (ITC). In contrast to our previous visual Go/NoGo study, no under-recruitment of task-relevant brain regions was found for the auditory theta and delta EROs. Young did not differ from older adults in RT variability or in single trial delta/theta ITC. Altered recruitment of brain activity at advanced age was indicated, first, by stronger early theta phase-locking in older compared to young adults and, second, by a Go-specific lateralization of delta/theta activity. We conclude that within-person variability may increase with age, but the degree depends on performance level and the modality investigated.

Occipital γ response to auditory stimulation in patients with schizophrenia.

This study investigated changes in gamma oscillations during auditory sensory processing (auditory-evoked gamma responses, AEGR) and target detection (auditory event-related gamma responses, AERGR) in healthy controls (n=10) and patients with schizophrenia (n=10) using both single-trial and averaged time-frequency data analysis. The results show that single-trial gamma responses in patients were altered in magnitude and topographic pattern for both the AEGR and the AERGR experimental conditions, whereas no differences were found for the averaged evoked gamma response. At the single-trial level, auditory stimuli elicited higher gamma responses at both anterior and occipital sites in patients with schizophrenia compared to controls. Furthermore, in patients with schizophrenia target detection compared to passive listening to stimuli was related to increased single-trial gamma power at frontal sites. In controls enhancement of the gamma response was only apparent for the averaged gamma response, with a distribution largely restricted to anterior sites. The differences in oscillatory activity between healthy controls and patients with schizophrenia were not reflected in the behavioral measure (i.e., counting targets). We conclude that gamma activity triggered by auditory stimuli in schizophrenic patients might have less selectivity in timing and alterations in topography and may show changes in amplitude modulation with task demands. The present study may indicate that in patients with schizophrenia neuronal information is not adequately transferred, possibly due to an over-excitability of neuronal networks and excessive pruning of local connections in association cortex.