High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Neuronale Synchronisation während perzeptueller Organisation in Schizophrenie-Patienten

Current theories of schizophrenia suggest that the pathophysiology of the disorder may be the result of a deficit in the coordination of neural activity within and between areas of the brain, which may lead to impairments in basic cognitive functions such as contextual disambiguation and dynamic grouping (Phillips and Silverstein, 2003). This notion has been supported by recent studies showing that patients with schizophrenia are characterized by reduced synchronous, oscillatory activity in the gamma-frequency band during sensory processing (Spencer et al. 2003, Green et al. 2003, Wynn et al. 2005). However, it is currently unclear to what extent high-frequency gamma-band oscillations (> 60 Hz) contribute to impaired neural synchronization as research has so far focussed on gamma-band oscillations between 30 and 60 Hz. In addition, it is not known whether deficits in high-frequency oscillations are already present at the onset of the disorder and to what extent reductions may be related to the confounding influence of antipsychotic medication. Finally, the neural generators underlying impairments in synchronous oscillatory activity in schizophrenia have not been investigated yet. To address these questions, we recorded MEG activity during a visual closure task (Mooney faces task) in medicated chronic schizophrenia patients, drug-naive first-episode schizophrenia patients and healthy controls. MEG data were analysed for spectral power between 25 and 150 Hz, and beamforming techniques were used to localize the sources of oscillatory gamma-band activity. In healthy controls, we observed that the processing of Mooney faces was associated with sustained high-frequency gamma-band activity (> 60 Hz). A time-resolved analysis of the neural generators underlying perceptual closure revealed a network of distributed sources in occipito-temporal, parietal and frontal regions, which were differentially activated during specific time intervals. In chronic schizophrenia patients, we found a pronounced reduction of high-frequency gamma-band oscillatory activity that was accompanied by an impairment in perceptual organization and involved reduced source power in various brain regions associated with perceptual closure. First-episode patients were also characterized by a deficit in high-frequency gamma-band activity and reductions of source power in multiple areas; these impairments, however, were less pronounced than in chronic patients. Regarding behavioral performance, first-episode patients were not impaired in their ability to detect Mooney faces, but exhibited a loss in specificity of face detection. In conclusion, our results suggest that schizophrenia is associated with a widespread reduction in high-frequency oscillations that indicate local network abnormalities. These dysfunctions are independent of medication status and already present at illness onset, suggesting a possible progressive deficit during the course of the disorder.Aktuelle Theorien gehen davon aus, dass die Pathophysiologie der Schizophrenie auf eine Störung in der Koordination neuronaler Prozesse zurückzuführen ist, welche zu einer Beeinträchtigung in der Integration von Informationen führt und sich in Defiziten bei frühen Wahrnehmungsprozessen und höheren kognitiven Funktionen widerspiegelt. Diese Hypothese wird durch eine Reihe von Studien gestützt, die eine Reduktion oszillatorischer Aktivität im Beta- und Gamma-Frequenzband im Elektroenzephalogramm während visueller Wahrnehmungsprozesse bei Patienten mit Schizophrenie nachweisen konnten. Die Bedeutung von hochfrequenten Gamma-Band Oszillationen (> 60 Hz) für das Verständnis von perzeptuellen Dysfunktionen bei Patienten mit Schizophrenie ist jedoch bislang wenig erforscht. Zudem ist unklar, ob und in welchem Umfang eine Veränderung oszillatorischer Aktivität bereits zu Beginn der Erkrankung und ohne den Einfluss von antipsychotischen Medikamenten vorhanden ist. Des Weiteren gibt es bislang keine Befunde zu den neuronalen Quellen, die den Defiziten oszillatorischer Aktivität bei Schizophrenie-Patienten zugrunde liegen. Um diese Fragen zu untersuchen, wurden im Rahmen der vorliegenden Dissertation drei Studien durchgeführt, in denen die Hirnaktivität während einer visuellen Gestaltaufgabe (Mooney faces-Aufgabe) bei chronischen medizierten Schizophrenie-Patienten, ersterkrankten nicht-medizierten Schizophrenie-Patienten sowie bei gesunden Kontrollprobanden mittels Magnetoenzephalographie (MEG) gemessen wurde. Die Auswertung der MEG-Daten beinhaltete auf der Sensoren-Ebene eine Auswertung der spektralen Power zwischen 25 und 150 Hz und auf der Quellen-Ebene eine Rekonstruktion der Generatoren oszillatorischer Aktivität mit Hilfe von Beamforming-Techniken. Die Hauptbefunde lassen sich wie folgt zusammenfassen: Das neuronale Netzwerk perzeptueller Organisation bei Mooney faces zeigte eine ausgeprägte oszillatorische Aktivität im hochfrequenten Gamma-Band (> 60 Hz) in gesunden Kontrollprobanden und umfasste okzipito-temporale, parietale und frontale Areale, die zu verschiedenen Zeitpunkten der Informationsverarbeitung aktiviert wurden. Unsere Ergebnisse lassen vermuten, dass perzeptuelle Organisationsprozesse bei Mooney faces auf einer frühen Interaktion zwischen Arealen beruhen, die mit der Verarbeitung von Schattierungsreizen zusammenhängen, gesichtsspezifischen Arealen, und Arealen, die mit dem Abruf von Informationen aus dem Langzeitgedächtnis in Verbindung stehen. Im Vergleich zu den Kontrollprobanden zeigten chronische Schizophrenie-Patienten ein deutliches Defizit in der hochfrequenten (60 – 120 Hz) Gamma-Band Power, welches mit reduzierten Detektionsraten bei der Mooney faces-Aufgabe und mit verringerten Aktivierungen in den für perzeptuelle Organisationsprozesse relevanten Arealen einherging. Ersterkrankte nicht-medizierte Schizophrenie-Patienten zeigten ebenfalls eine Reduktion hochfrequenter Gamma-Band Power in verschiedenen Hirnarealen. Dieses Defizit war jedoch weniger stark ausgeprägt als in den chronischen Schizophrenie-Patienten. Im Gegensatz zu den chronischen Patienten zeigten die ersterkrankten Patienten keine Beeinträchtigung bei der Detektion von Gesichtern in aufrecht präsentierten Mooney face Stimuli; jedoch wiesen sie ein Defizit in der Diskrimination zwischen Gesichtern und Nicht-Gesichtern auf. Unsere Befunde deuten darauf hin, dass bei Patienten mit Schizophrenie ausgeprägte Defizite in lokalen Synchronisationsprozessen vorliegen, welche mit perzeptuellen Dysfunktionen einhergehen. Die beeinträchtigte Koordination neuronaler Aktivität könnte auf Veränderungen in GABAergen und glutamatergen Neurotransmittersystemen bei Schizophrenie-Patienten zurückzuführen sein. Unsere Ergebnisse zeigen weiterhin, dass Beeinträchtigungen neuronaler Synchronisation bereits zu Beginn der Erkrankung und ohne den Einfluss von antipsychotischer Medikation vorhanden sind. Die stärkere Beeinträchtigung in den chronischen im Vergleich zu den ersterkrankten Patienten deutet auf einen progressiven Verlauf der Beeinträchtigung oszillatorischer Aktivität bei Schizophrenie-Patienten hin

Long-Range Temporal Correlations in Resting State Beta Oscillations are Reduced in Schizophrenia

Symptoms of schizophrenia (SCZ) are likely to be generated by genetically mediated synaptic dysfunction, which contribute to large-scale functional neural dysconnectivity. Recent electrophysiological studies suggest that this dysconnectivity is present not only at a spatial level but also at a temporal level, operationalized as long-range temporal correlations (LRTCs). Previous research suggests that alpha and beta frequency bands have weaker temporal stability in people with SCZ. This study sought to replicate these findings with high-density electroencephalography (EEG), enabling a spatially more accurate analysis of LRTC differences, and to test associations with characteristic SCZ symptoms and cognitive deficits. A 128-channel EEG was used to record eyes-open resting state brain activity of 23 people with SCZ and 24 matched healthy controls (HCs). LRTCs were derived for alpha (8–12 Hz) and beta (13–25 Hz) frequency bands. As an exploratory analysis, LRTC was source projected using sLoreta. People with SCZ showed an area of significantly reduced beta-band LRTC compared with HCs over bilateral posterior regions. There were no between-group differences in alpha-band activity. Individual symptoms of SCZ were not related to LRTC values nor were cognitive deficits. The study confirms that people with SCZ have reduced temporal stability in the beta frequency band. The absence of group differences in the alpha band may be attributed to the fact that people had, in contrast to previous studies, their eyes open in the current study. Taken together, our study confirms the utility of LRTC as a marker of network instability in people with SCZ and provides a novel empirical perspective for future examinations of network dysfunction salience in SCZ research

Parietal tACS at beta frequency improves vision in a crowding regime

Abstract Visual crowding is the inability to discriminate objects when presented with nearby flankers and sets a fundamental limit for conscious perception. Beta oscillations in the parietal cortex were found to be associated to crowding, with higher beta amplitude related to better crowding resilience. An open question is whether beta activity directly and selectively modulates crowding. We employed transcranial alternating current stimulation (tACS) in the beta band (18-Hz), in the alpha band (10-Hz) or in a sham regime, asking whether 18-Hz tACS would selectively improve the perception of crowded stimuli by increasing parietal beta activity. Resting electroencephalography (EEG) was measured before and after stimulation to test the influence of tACS on endogenous oscillations. Consistently with our predictions, we found that 18-Hz tACS, as compared to 10-Hz tACS and sham stimulation, reduced crowding. This improvement was found specifically in the contralateral visual hemifield and was accompanied by an increased amplitude of EEG beta oscillations, confirming an effect on endogenous brain rhythms. These results support a causal relationship between parietal beta oscillations and visual crowding and provide new insights into the precise oscillatory mechanisms involved in human vision

Spectral parameters modulation and source localization of blink-related alpha and low-beta oscillations differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome

Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n=13 pairs+4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n=15). Results: In the resting state, there was a significant condition × frequency interaction (p=0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p=0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r=0.429, p=0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p=0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p=0.02) and not the 65–85-Hz band. Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state

Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in schizophrenia

Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25–150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60–120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder