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

MEG-measured auditory steady-state oscillations show high test-retest reliability: a sensor and source-space analysis

Stability of oscillatory signatures across magnetoencephalography (MEG) measurements is an important prerequisite for basic and clinical research that has been insufficiently addressed. Here, we evaluated the test–retest reliability of auditory steady-state responses (ASSRs) over two MEG sessions. The study required participants (N = 13) to detect the rare occurrence of pure tones interspersed within a stream of 5 Hz or 40 Hz amplitude-modulated (AM) tones. Intraclass correlations (ICC; Shrout and Fleiss, 1979) were derived to assess stability of spectral power changes and the inter-trial phase coherence (ITPC) of task-elicited neural responses. ASSRs source activity was estimated using eLORETA beamforming from bilateral auditory cortex. ASSRs to 40 Hz AM stimuli evoked stronger power modulation and phase-locking than 5 Hz stimulation. Overall, spectral power and ITPC values at both sensor- and source-level showed robust ICC values. Notably, ITPC measures yielded higher ICCs (~ 0.86–0.96) between sessions compared to the assessment of spectral power change (~ 0.61–0.82). Our data indicate that spectral modulations and phase consistency of ASSRs in MEG data are highly reproducible, providing support for MEG-measured oscillatory parameters in basic and clinical research

Deep brain stimulation in schizophrenia

Deep brain stimulation (DBS) has successfully advanced treatment options of putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronization. In conclusion the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might void the use of DBS in schizophrenia at this point

Deep brain stimulation in schizophrenia

Deep brain stimulation (DBS) has successfully advanced treatment options of putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronization. In conclusion the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might void the use of DBS in schizophrenia at this point

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis:An ENIGMA Working Group Mega-analysis

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not

High-Frequency Oscillations in Schizophrenia

Neural oscillations and their synchronization may represent a versatile signal to realize flexible communication within and between cortical areas. There is extensive evidence that cognitive functions depending on coordination of distributed neural responses are associated with synchronized oscillatory activity, suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia, that involve dysfunctional cognition and behavior. In the present paper, the focus is on the role of high-frequency oscillations for cortical computations through establishing correlations between the modulation of oscillations in the β/γ frequency range and specific cognitive processes during normal brain functioning and in schizophrenia. Specifically, it is suggested that in addition to oscillations in the low (30–60 Hz) γ-band range, γ-band oscillations &gt; 60 Hz may have a crucial role for the understanding of cognitive dysfunctions in schizophrenia. Perspectives for future research will be discussed in relationship to methodological issues, the utility of neural oscillations as a biomarker and the neurodevelopmental hypothesis of schizophrenia. </jats:p

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

Schizophrenia remains a daunting challenge for efforts aimed at identifying fundamental pathophysiological processes and to develop evidence-based effective treatments and interventions. One reason for the lack of progress lies in the fact that the pathophysiology of schizophrenia has been predominantly conceived in terms of circumscribed alterations in cellular and anatomical variables. In the current review, it is proposed that this approach needs to be complemented by a focus on the neuronal dynamics in large-scale networks which is compatible with the notion of dysconnectivity, highlighting the involvement of both reduced and increased interactions in extended cortical circuits in schizophrenia. Neural synchrony is one candidate mechanisms for achieving functional connectivity in large-scale networks and has been found to be impaired in schizophrenia. Importantly, alterations in the synchronization of neural oscillations can be related to dysfunctions in the excitation–inhibition (E/I)-balance and developmental modifications with important implications for translational research

The phase of thalamic alpha activity modulates cortical gamma-band activity: evidence from resting-state MEG recordings

Recent findings have implicated thalamic alpha oscillations in the phasic modulation of cortical activity. However, the precise relationship between thalamic alpha oscillations and neocortical activity remains unclear. Here we show in a large sample of healthy human participants (n = 45) using spatial filtering techniques and measures of phase amplitude coupling that the amplitude of gamma-band activity in posterior medial parietal cortex is modulated by the phase of thalamic alpha oscillations during eyes-closed resting-state recordings. In addition, our findings show that gamma-band activity in visual cortex was not modulated by thalamic alpha oscillations but coupled to the phase of strong cortical alpha activity. To overcome the limitations of electromagnetic source localization we estimated conduction delays using transfer entropy and found nonspurious information transfer from thalamus to cortex. The present findings provide novel evidence for magneto-encephalography-measured phase coupling between cortical gamma-band activity and thalamic alpha oscillations, which highlight the role of phasic inhibition in the coordination of cortical activity

Gamma-band activity in human prefrontal cortex codes for the number of relevant items maintained in working memory

Previous studies in electrophysiology have provided consistent evidence for a relationship between neural oscillations in different frequency bands and the maintenance of information in working memory (WM). While the amplitude and cross-frequency coupling of neural oscillations have been shown to be modulated by the number of items retained during WM, interareal phase synchronization has been associated with the integration of distributed activity during WM maintenance. Together, these findings provided important insights into the oscillatory dynamics of cortical networks during WM. However, little is known about the cortical regions and frequencies that underlie the specific maintenance of behaviorally relevant information in WM. In the current study, we addressed this question with magnetoencephalography and a delayed match-to-sample task involving distractors in 25 human participants. Using spectral analysis and beamforming, we found a WM load-related increase in the gamma band (60–80 Hz) that was localized to the right intraparietal lobule and left Brodmann area 9 (BA9). WM-load related changes were also detected at alpha frequencies (10–14 Hz) in Brodmann area 6, but did not covary with the number of relevant WM-items. Finally, we decoded gamma-band source activity with a linear discriminant analysis and found that gamma-band activity in left BA9 predicted the number of target items maintained in WM. While the present data show that WM maintenance involves activity in the alpha and gamma band, our results highlight the specific contribution of gamma band delay activity in prefrontal cortex for the maintenance of behaviorally relevant items