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Magnetoencephalography (MEG) allows the non-invasive measurement of brain activity at millisecond precision combined with localization of the underlying generators. So far, MEG-systems consisted of superconducting quantum interference devices (SQUIDS), which suffer from several limitations. Recent technological advances, however, have enabled the development of novel MEG-systems based on optically pumped magnetometers (OPMs), offering several advantages over conventional SQUID-MEG systems. Considering potential improvements in the measurement of neuronal signals as well as reduced operating costs, the application of OPM-MEG systems for clinical neuroscience and diagnostic settings is highly promising. Here we provide an overview of the current state-of-the art of OPM-MEG and its unique potential for translational neuroscience. First, we discuss the technological features of OPMs and benchmark OPM-MEG against SQUID-MEG and electroencephalography (EEG), followed by a summary of pioneering studies of OPMs in healthy populations. Key applications of OPM-MEG for the investigation of psychiatric and neurological conditions are then reviewed. Specifically, we suggest novel applications of OPM-MEG for the identification of biomarkers and circuit deficits in schizophrenia, dementias, movement disorders, epilepsy, and neurodevelopmental syndromes (autism spectrum disorder and attention deficit hyperactivity disorder). Finally, we give an outlook of OPM-MEG for translational neuroscience with a focus on remaining methodological and technical challenges., (© 2024. The Author(s).)

Background: Impairments in language processing in schizophrenia (ScZ) are a central aspect of the disorder but the underlying pathophysiology mechanisms are unclear. In the current study, we tested the hypothesis that neural oscillations are impaired during speech tracking in early-stage ScZ and in participants at clinical high-risk for psychosis (CHR-P)., Method: Magnetoencephalography (MEG) was used in combination with source reconstructed time-series to examine delta and theta-band entrainment during continuous speech. Participants were presented with a 5-minute audio recording during which they either attened to the story or word level. MEG-data were obtained from n = 22 CHR-P participants, n = 23 early-stage ScZ-patients, and n = 44 healthy controls (HC). Data were analysed with a Mutual Information (MI) approach to compute statistical dependence between the MEG and auditory signal, thus estimating individual speech-tracking ability. MEG-activity was reconstructed in a language network (bilateral inferior frontal cortex [F3T; Broca's], superior temporal areas [STS3, STS4; Wernicke's areas], and primary auditory cortex [bilateral HES; Heschl's gyrus]). MEG-data were correlated with clinical symptoms., Results: Theta-band entrainment in left Heschl's gyrus, averaged across groups, was significantly lower in the STORY compared to WORD condition (p = 0.022), and averaged over conditions, significantly lower in CHR-Ps (p = 0.045), but intact in early ScZ patients (p = 0.303), compared to controls. Correlation analyses between MEG data and symptom indicated that lower theta-band tracking in CHR-Ps was linked to the severity of perceptual abnormalities (p = 0.018)., Conclusion: Our results show that CHR-P participants involve impairments in theta-band entrainment during speech tracking in left primary auditory cortex while higher-order speech processing areas were intact. Moreover, the severity of aberrant perceptual experiences in CHR-P participants correlated with deficits in theta-band entrainment. Together, these findings highlight the possibility that neural oscillations during language processing could reveal fundamental abnormalities in speech processing which may constitute candidate biomarkers for early detection and diagnosis of ScZ., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps., Methods: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri., Results: Significant magnetic MMN responses were found across participants in the bilateral Heschl's gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants., Conclusions: Our data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Reduced auditory mismatch negativity (MMN) is robustly impaired in schizophrenia. However, mechanisms underlying dysfunctional MMN generation remain incompletely understood. This study aimed to examine the role of evoked spectral power and phase-coherence towards deviance detection and its impairments in schizophrenia., Methods: Magnetoencephalography data was collected in 16 male schizophrenia patients and 16 male control participants during an auditory MMN paradigm. Analyses of event-related fields (ERF), spectral power and inter-trial phase-coherence (ITPC) focused on Heschl's gyrus, superior temporal gyrus, inferior/medial frontal gyrus and thalamus., Results: MMNm ERF amplitudes were reduced in patients in temporal, frontal and subcortical regions, accompanied by decreased theta-band responses, as well as by a diminished gamma-band response in auditory cortex. At theta/alpha frequencies, ITPC to deviant tones was reduced in patients in frontal cortex and thalamus. Patients were also characterized by aberrant responses to standard tones as indexed by reduced theta-/alpha-band power and ITPC in temporal and frontal regions. Moreover, stimulus-specific adaptation was decreased at theta/alpha frequencies in left temporal regions, which correlated with reduced MMNm spectral power and ERF amplitude. Finally, phase-reset of alpha-oscillations after deviant tones in left thalamus was impaired, which correlated with impaired MMNm generation in auditory cortex. Importantly, both non-rhythmic and rhythmic components of spectral activity contributed to the MMNm response., Conclusions: Our data indicate that deficits in theta-/alpha- and gamma-band activity in cortical and subcortical regions as well as impaired spectral responses to standard sounds could constitute potential mechanisms for dysfunctional MMN generation in schizophrenia, providing a novel perspective towards MMN deficits in the disorder., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter J. Uhlhaas reports financial support was provided by German Israeli Foundation for Scientific Research and Development. Abraham Goldstein reports financial support was provided by German Israeli Foundation for Scientific Research and Development., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is converging evidence that 40-Hz auditory steady-state responses (ASSRs) are robustly impaired in schizophrenia and could constitute a potential biomarker for characterizing circuit dysfunctions as well as enable early detection and diagnosis. Here, we provide an overview of the mechanisms involved in 40-Hz ASSRs, drawing on computational, physiological, and pharmacological data with a focus on parameters modulating the balance between excitation and inhibition. We will then summarize findings from electro- and magnetoencephalographic studies in participants at clinical high risk for psychosis, patients with first-episode psychosis, and patients with schizophrenia to identify the pattern of deficits across illness stages, the relationship with clinical variables, and the prognostic potential. Finally, data on genetics and developmental modifications will be reviewed, highlighting the importance of late modifications of 40-Hz ASSRs during adolescence, which are closely related to the underlying changes in GABA (gamma-aminobutyric acid) interneurons. Together, our review suggests that 40-Hz ASSRs may constitute an informative electrophysiological approach to characterize circuit dysfunctions in psychosis that could be relevant for the development of mechanistic biomarkers., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Evidence suggests that schizophrenia (ScZ) involves impairments in sensory attenuation. It is currently unclear, however, whether such deficits are present during early-stage psychosis as well as the underlying network and the potential as a biomarker. To address these questions, Magnetoencephalography (MEG) was used in combination with computational modeling to examine M100 responses that involved a "passive" condition during which tones were binaurally presented, while in an "active" condition participants were asked to generate a tone via a button press. MEG data were obtained from 109 clinical high-risk for psychosis (CHR-P) participants, 23 people with a first-episode psychosis (FEP), and 48 healthy controls (HC). M100 responses at sensor and source level in the left and right thalamus (THA), Heschl's gyrus (HES), superior temporal gyrus (STG) and right inferior parietal cortex (IPL) were examined and dynamic causal modeling (DCM) was performed. Furthermore, the relationship between sensory attenuation and persistence of attenuated psychotic symptoms (APS) and transition to psychosis was investigated in CHR-P participants. Sensory attenuation was impaired in left HES, left STG and left THA in FEP patients, while in the CHR-P group deficits were observed only in right HES. DCM results revealed that CHR-P participants showed reduced top-down modulation from the right IPL to the right HES. Importantly, deficits in sensory attenuation did not predict clinical outcomes in the CHR-P group. Our results show that early-stage psychosis involves impaired sensory attenuation in auditory and thalamic regions but may not predict clinical outcomes in CHR-P participants., (© 2023. The Author(s).)

Background: Numerous behavioral studies have highlighted the contribution of visual perceptual deficits to the nonverbal cognitive profile of individuals with 22q11.2 deletion syndrome. However, the neurobiological processes underlying these widespread behavioral alterations are yet to be fully understood. Thus, in this paper, we investigated the role of neural oscillations toward visuoperceptual deficits to elucidate the neurobiology of sensory impairments in deletion carriers., Methods: We acquired 125 high-density electroencephalography recordings during a visual grating task in a group of 62 deletion carriers and 63 control subjects. Stimulus-elicited oscillatory responses were analyzed with 1) time-frequency analysis using wavelets decomposition at sensor and source level, 2) intertrial phase coherence, and 3) Granger causality connectivity in source space. Additional analyses examined the development of neural oscillations across age bins., Results: Deletion carriers had decreased theta-band (4-8 Hz) and gamma-band (58-68 Hz) spectral power compared with control subjects in response to the visual stimuli, with an absence of age-related increase of theta- and gamma-band responses. Moreover, adult deletion carriers had decreased gamma- and theta-band responses but increased alpha/beta desynchronization (10-25 Hz) that correlated with behavioral performance. Granger causality estimates reflected an increased frontal-occipital connectivity in the beta range (22-40 Hz)., Conclusions: Deletion carriers exhibited decreased theta- and gamma-band responses to visual stimuli, while alpha/beta desynchronization was preserved. Overall, the lack of age-related changes in deletion carriers implicates developmental impairments in circuit mechanisms underlying neural oscillations. The dissociation between the maturation of theta/gamma- and alpha/beta-band responses may indicate a selective impairment in supragranular cortical layers, leading to compensatory top-down connectivity., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P ( n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal ( p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels ( p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls ( p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grent-’t-Jong, Gajwani, Gross, Gumley, Lawrie, Schwannauer, Schultze-Lutter, Williams and Uhlhaas.)

Recently, Vesuna et al. proposed a novel circuit mechanism underlying dissociative states using optogenetics and pharmacology in mice in combination with intracranial recordings and electrical stimulation in an epilepsy patient. Specifically, the authors identified a posteromedial cortical delta-rhythm that underlies states of dissociation. In the following, we would like to critically review these findings in the context of the human literature on dissociation as well as highlight the challenges in translational neuroscience to link complex behavioral phenotypes in psychiatric syndromes to circumscribed circuit mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grent-'t-Jong, Melloni and Uhlhaas.)

Background: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes., Methods: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naïve), a psychosis risk-negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl's gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs)., Results: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl's gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl's gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695)., Conclusions: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Long-Range Temporal Correlations (LRTCs) index the capacity of the brain to optimally process information. Previous research has shown that patients with chronic schizophrenia present altered LRTCs at alpha and beta oscillations. However, it is currently unclear at which stage of schizophrenia aberrant LRTCs emerge. To address this question, we investigated LRTCs in resting-state magnetoencephalographic (MEG) recordings obtained from patients with affective disorders and substance abuse (clinically at low-risk of psychosis, CHR-N), patients at clinical high-risk of psychosis (CHR-P) (n = 115), as well as patients with a first episode (FEP) (n = 25). Matched healthy controls (n = 47) served as comparison group. LRTCs were obtained for frequencies from 4 to 40 Hz and correlated with clinical and neuropsychological data. In addition, we examined the relationship between LRTCs and transition to psychosis in CHR-P participants, and the relationship between LRTC and antipsychotic medication in FEP participants. Our results show that participants from the clinical groups have similar LRTCs to controls. In addition, LRTCs did not correlate with clinical and neurocognitive variables across participants nor did LRTCs predict transition to psychosis. Therefore, impaired LRTCs do not reflect a feature in the clinical trajectory of psychosis. Nevertheless, reduced LRTCs in the beta-band over posterior sensors of medicated FEP participants indicate that altered LRTCs may appear at the onset of the illness. Future studies are needed to elucidate the role of anti-psychotic medication in altered LRTCs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunctions represent a core feature of schizophrenia and a predictor for clinical outcomes. One possible mechanism for cognitive impairments could involve an impairment in the experience-dependent modifications of cortical networks. Methods: To address this issue, we employed magnetoencephalography (MEG) during a visual priming paradigm in a sample of chronic patients with schizophrenia ( n = 14), and in a group of healthy controls ( n = 14). We obtained MEG-recordings during the presentation of visual stimuli that were presented three times either consecutively or with intervening stimuli. MEG-data were analyzed for event-related fields as well as spectral power in the 1-200 Hz range to examine repetition suppression and repetition enhancement. We defined regions of interest in occipital and thalamic regions and obtained virtual-channel data. Results: Behavioral priming did not differ between groups. However, patients with schizophrenia showed prominently reduced oscillatory response to novel stimuli in the gamma-frequency band as well as significantly reduced repetition suppression of gamma-band activity and reduced repetition enhancement of beta-band power in occipital cortex to both consecutive repetitions as well as repetitions with intervening stimuli. Moreover, schizophrenia patients were characterized by a significant deficit in suppression of the C1m component in occipital cortex and thalamus as well as of the late positive component (LPC) in occipital cortex. Conclusions: These data provide novel evidence for impaired repetition suppression in cortical and subcortical circuits in schizophrenia. Although behavioral priming was preserved, patients with schizophrenia showed deficits in repetition suppression as well as repetition enhancement in thalamic and occipital regions, suggesting that experience-dependent modification of neural circuits is impaired in the disorder., (Copyright © 2020 Sauer, Grent-'t-Jong, Wibral, Grube, Singer and Uhlhaas.)

Introduction: Alterations in autonomic functioning in individuals diagnosed with schizophrenia are well-documented. Yet, it is currently unclear whether these dysfunctions extend into the clinical high-risk state. Thus, we investigated resting heart rate (RHR) and heart rate variability (HRV) indices in individuals at clinical high-risk for psychosis (CHR-P). Methods: We recruited 117 CHR-P participants, 38 participants with affective disorders and substance abuse (CHR-N) as well as a group of 49 healthy controls. CHR-P status was assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). We obtained 5 min, eyes-open resting-state MEG data, which was used for the extraction of cardiac field-related inter-beat-interval data and from which heart-rate and heart-rate variability measures were computed. Results: Compared to both CHR-N and healthy controls, CHR-P participants were characterized by an increased RHR, which was not explained by differences in psychopathological comorbidity and medication status. Increased RHR correlated with the presence of subthreshold psychotic symptoms and associated distress. No differences between groups were found for heart-rate variability measures, however. Furthermore, there was an association between motor-performance and psychophysiological measures. Conclusion: The current study provides evidence of alterations in autonomic functioning as disclosed by increased RHR in CHR-P participants. Future studies are needed to further evaluate this characteristic feature of CHR-P individuals and its potential predictive value for psychosis development., (Copyright © 2020 Kocsis, Gajwani, Gross, Gumley, Lawrie, Schwannauer, Schultze-Lutter, Grent-‘t-Jong and Uhlhaas.)

Sensory attenuation refers to the decreased intensity of a sensory percept when a sensation is self-generated compared with when it is externally triggered. However, the underlying brain regions and network interactions that give rise to this phenomenon remain to be determined. To address this issue, we recorded magnetoencephalographic (MEG) data from 35 healthy controls during an auditory task in which pure tones were either elicited through a button press or passively presented. We analyzed the auditory M100 at sensor- and source-level and identified movement-related magnetic fields (MRMFs). Regression analyses were used to further identify brain regions that contributed significantly to sensory attenuation, followed by a dynamic causal modeling (DCM) approach to explore network interactions between generators. Attenuation of the M100 was pronounced in right Heschl's gyrus (HES), superior temporal cortex (ST), thalamus, rolandic operculum (ROL), precuneus and inferior parietal cortex (IPL). Regression analyses showed that right postcentral gyrus (PoCG) and left precentral gyrus (PreCG) predicted M100 sensory attenuation. In addition, DCM results indicated that auditory sensory attenuation involved bi-directional information flow between thalamus, IPL, and auditory cortex. In summary, our data show that sensory attenuation is mediated by bottom-up and top-down information flow in a thalamocortical network, providing support for the role of predictive processing in sensory-motor system., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Importance: Psychotic disorders are characterized by impairments in neural oscillations, but the nature of the deficit, the trajectory across illness stages, and functional relevance remain unclear., Objectives: To examine whether changes in spectral power, phase locking, and functional connectivity in visual cortex are present during emerging psychosis and whether these abnormalities are associated with clinical outcomes., Design, Setting, and Participants: In this cross-sectional study, participants meeting clinical high-risk criteria for psychosis, participants with first-episode psychosis, participants with affective disorders and substance abuse, and a group of control participants were recruited. Participants underwent measurements with magnetoencephalography and magnetic resonance imaging. Data analysis was carried out between 2018 and 2019., Main Outcomes and Measures: Magnetoencephalographical activity was examined in the 1- to 90-Hz frequency range in combination with source reconstruction during a visual grating task. Event-related fields, power modulation, intertrial phase consistency, and connectivity measures in visual and frontal cortices were associated with neuropsychological scores, psychosocial functioning, and clinical symptoms as well as persistence of subthreshold psychotic symptoms at 12 months., Results: The study participants included those meeting clinical high-risk criteria for psychosis (n = 119; mean [SD] age, 22 [4.4] years; 32 men), 26 patients with first-episode psychosis (mean [SD] age, 24 [4.2] years; 16 men), 38 participants with affective disorders and substance abuse (mean [SD] age, 23 [4.7] years; 11 men), and 49 control participants (mean age [SD], 23 [3.6] years; 16 men). Clinical high-risk participants and patients with first-episode psychosis were characterized by reduced phase consistency of β/γ-band oscillations in visual cortex (d = 0.63/d = 0.93). Moreover, the first-episode psychosis group was also characterized by reduced occipital γ-band power (d = 1.14) and altered visual cortex connectivity (d = 0.74-0.84). Impaired fronto-occipital connectivity was present in both clinical high-risk participants (d = 0.54) and patients with first-episode psychosis (d = 0.84). Importantly, reductions in intertrial phase coherence predicted persistence of subthreshold psychosis in clinical high-risk participants (receiver operating characteristic area under curve = 0.728; 95% CI, 0.612-0.841; P = .001)., Conclusions and Relevance: High-frequency oscillations are impaired in the visual cortex during emerging psychosis and may be linked to behavioral and clinical impairments. Impaired phase consistency of γ-band oscillations was also associated with the persistence of subthreshold psychosis, suggesting that magnetoencephalographical measured neural oscillations could constitute a biomarker for clinical staging of emerging psychosis.

The identification of biomarkers for the early diagnosis of schizophrenia that could inform novel treatment developments is an important objective of current research. This paper will summarize recent work that has investigated changes in oscillatory activity and event-related potentials with Electro/Magnetoencephalography (EEG/MEG) in participants at high-risk for the development of schizophrenia, highlighting disruptions in sensory and cognitive operations prior to the onset of the syndrome. Changes in EEG/MEG-data are consistent with evidence for alterations in Glutamatergic and GABAergic neurotransmission as disclosed by Magnetic Resonance Spectroscopy and brain stimulation, indicating changes in Excitation/Inhibition balance parameters prior to the onset of psychosis. Together these data emphasize the importance of research into neuronal dynamics as a crucial approach to establish functional relationships between impairments in neural circuits and emerging psychopathology that together could be fundamental for early intervention and the identification of novel treatments for emerging psychosis., (Copyright © 2017. Published by Elsevier Inc.)

We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64-90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ., Competing Interests: TG, JG, JG, MW, RG, AG, SL, MS, FS, TN, DK, FL, WS, PU No competing interests declared, (© 2018, Grent-'t-Jong et al.)

Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1-90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63-80 Hz) in occipital regions and upregulated low frequency (5-28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082-5093, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The thalamus has recently received renewed interest in systems-neuroscience and schizophrenia (ScZ) research because of emerging evidence highlighting its important role in coordinating functional interactions in cortical-subcortical circuits. Moreover, higher cognitive functions, such as working memory and attention, have been related to thalamo-cortical interactions, providing a novel perspective for the understanding of the neural substrate of cognition. The current review will support this perspective by summarizing evidence on the crucial role of neural oscillations in facilitating thalamo-cortical (TC) interactions during normal brain functioning and their potential impairment in ScZ. Specifically, we will focus on the relationship between NMDA-R mediated (glutamatergic) neurotransmission in TC-interactions. To this end, we will first review the functional anatomy and neurotransmitters in thalamic circuits, followed by a review of the oscillatory signatures and cognitive processes supported by TC-circuits. In the second part of the paper, data from preclinical research as well as human studies will be summarized that have implicated TC-interactions as a crucial target for NMDA-receptor hypofunctioning. Finally, we will compare these neural signatures with current evidence from ScZ-research, suggesting a potential overlap between alterations in TC-circuits as the result of NMDA-R deficits and stage-specific alterations in large-scale networks in ScZ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Gamma-band oscillations are prominently impaired in schizophrenia, but the nature of the deficit and relationship to perceptual processes is unclear., Methods: 16 patients with chronic schizophrenia (ScZ) and 16 age-matched healthy controls completed a visual paradigm while magnetoencephalographic (MEG) data was recorded. Participants had to detect randomly occurring stimulus acceleration while viewing a concentric moving grating. MEG data were analyzed for spectral power (1-100Hz) at sensor- and source-level to examine the brain regions involved in aberrant rhythmic activity, and for contribution of differences in baseline activity towards the generation of low- and high-frequency power., Results: Our data show reduced gamma-band power at sensor level in schizophrenia patients during stimulus processing while alpha-band and baseline spectrum were intact. Differences in oscillatory activity correlated with reduced behavioral detection rates in the schizophrenia group and higher scores on the "Cognitive Factor" of the Positive and Negative Syndrome Scale. Source reconstruction revealed that extra-striate (fusiform/lingual gyrus), but not striate (cuneus), visual cortices contributed towards the reduced activity observed at sensor-level in ScZ patients. Importantly, differences in stimulus-related activity were not due to differences in baseline activity., Conclusions: Our findings highlight that MEG-measured high-frequency oscillations during visual processing can be robustly identified in ScZ. Our data further suggest impairments that involve dysfunctions in ventral stream processing and a failure to increase gamma-band activity in a task-context. Implications of these findings are discussed in the context of current theories of cortical-subcortical circuit dysfunctions and perceptual processing in ScZ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Choice behavior is influenced by factors such as reward and number of alternatives but also by physical context, for instance, the relative position of alternative movement targets. At small separation, speeded eye or hand movements are more likely to land between targets (spatial averaging) than at larger separation. Neurocomputational models explain such behavior in terms of cortical activity being preshaped by the movement environment. Here, we manipulate target separation, as a determinant of motor cortical activity in choice behavior, to address neural mechanisms of response selection. Specifically, we investigate whether context-induced changes in the balance of cooperative and competitive interactions between competing groups of neurons are expressed in the power spectrum of sensorimotor rhythms. We recorded magnetoencephalography while participants were precued to two possible movement target locations at different angles of separation (30, 60, or 90°). After a delay, one of the locations was cued as the target for a joystick pointing movement. We found that late delay-period movement-preparatory activity increased more strongly for alternative targets at 30 than at 60 or 90° of separation. This nonlinear pattern was evident in slow event-related fields as well as in beta- and low-gamma-band suppression. A comparable pattern was found within an earlier window for theta-band synchronization. We interpret the late delay effects in terms of increased movement-preparatory activity when there is greater overlap and hence less competition between groups of neurons encoding two response alternatives. Early delay-period theta-band synchronization may reflect covert response activation relevant to behavioral spatial averaging effects., (Copyright © 2014 the American Physiological Society.)

Neurophysiological studies in non-human primates have provided evidence for simultaneous activation of competing responses in the (pre)motor cortex. Human evidence, however, is limited, partly because experimental approaches have often mapped competing responses to paired effectors represented in opposite hemispheres, which restricts the analysis to between-hemisphere comparisons and allows simultaneous execution. A demonstration of competition between different movement plans in the motor cortex is more compelling when simultaneous execution of the alternative responses is ruled out and they are represented in one motor cortex. Therefore, in the current MEG study we have used a unimanual Eriksen flanker paradigm with alternative responses assigned to flexion and extension of the right index finger, activating different direction-sensitive neurons within the finger representation area of the same motor cortex. Results showed that for stimuli eliciting response competition the pre-response motor cortex beta-band (17-29 Hz) power decreased stronger than for stimuli that did not induce response competition. Furthermore, response competition elicited an additional pre-response mid-frontal high-gamma band (60-90 Hz) power increase. Finally, larger gamma-band effect sizes correlated with greater behavioral response delay induced by response competition. Taken together, our results provide evidence for co-activation of competing responses in the human brain, consistent with evidence from non-human primates., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Markers of preparatory visual-spatial attention in sensory cortex have been described both as lateralized, slow-wave event-related potential (ERP) components and as lateralized changes in oscillatory-electroencephalography alpha power, but the roles of these markers and their functional relationship are still unclear. Here, 3 versions of a visual-spatial cueing paradigm, differing in perceptual task difficulty and/or response instructions, were used to investigate the functional relationships between posterior oscillatory-alpha changes and our previously reported posterior, slow-wave biasing-related negativity (swBRN) ERP activity. The results indicate that the swBRN reflects spatially specific, pretarget preparatory activity sensitive to the expected perceptual difficulty of the target detection task, correlating in both location and strength with the early sensory-processing N1 ERP to the target, consistent with reflecting a preparatory baseline-shift mechanism. In contrast, contralateral event-related decreases in alpha-band power were relatively insensitive to perceptual difficulty and differed topographically from both the swBRN and target N1. Moreover, when response instructions emphasized making immediate responses to targets, compared with prescribing delayed responses, contralateral alpha-event-related desynchronization activity was particularly strong and correlated with the longer latency target-P3b activity. Thus, in contrast to the apparent perceptual-biasing role of swBRN activity, contralateral posterior alpha activity may represent an attentionally maintained task set linking stimulus-specific information and task-specific response requirements.

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated a frontal-parietal network in the top-down control of attention. However, little is known about the timing and sequence of activations within this network. To investigate these timing questions, we used event-related electrical brain potentials (ERPs) and a specially designed visual-spatial attentional-cueing paradigm, which were applied as part of a multi-methodological approach that included a closely corresponding event-related fMRI study using an identical paradigm. In the first 400 ms post cue, attention-directing and control cues elicited similar general cue-processing activity, corresponding to the more lateral subregions of the frontal-parietal network identified with the fMRI. Following this, the attention-directing cues elicited a sustained negative-polarity brain wave that was absent for control cues. This activity could be linked to the more medial frontal-parietal subregions similarly identified in the fMRI as specifically involved in attentional orienting. Critically, both the scalp ERPs and the fMRI-seeded source modeling for this orienting-related activity indicated an earlier onset of frontal versus parietal contribution ( approximately 400 versus approximately 700 ms). This was then followed ( approximately 800-900 ms) by pretarget biasing activity in the region-specific visual-sensory occipital cortex. These results indicate an activation sequence of key components of the attentional-control brain network, providing insight into their functional roles. More specifically, these results suggest that voluntary attentional orienting is initiated by medial portions of frontal cortex, which then recruit medial parietal areas. Together, these areas then implement biasing of region-specific visual-sensory cortex to facilitate the processing of upcoming visual stimuli., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Event-related potential (ERP) studies have shown that emotional stimuli elicit greater amplitude late positive-polarity potentials (LPPs) than neutral stimuli. This effect has been attributed to arousal, but emotional stimuli are also more semantically coherent than uncategorized neutral stimuli. ERPs were recorded during encoding of positive, negative, uncategorized neutral, and categorized neutral words. Differences in LPP amplitude elicited by emotional versus uncategorized neutral stimuli were evident from 450 to 1000 ms. From 450 to 700 ms, LPP effects at midline and right hemisphere frontal electrodes indexed arousal, whereas LPP effects at left hemisphere centro-parietal electrodes indexed semantic cohesion. This dissociation helps specify the processes underlying emotional stimulus encoding, and suggests the need to control for semantic cohesion in emotional information processing studies.

In the present study, we investigated control of selective attention to spatial frequency patterns, using a cueing paradigm. Subjects either used the instruction embedded in a word cue to prepare for the upcoming test stimulus (transient attention condition) or used the instruction they received before a block of trials (sustained reference condition), under completely similar stimulus conditions. The pattern of differential cue responses between these two conditions, reflecting top-down attentional control processes, was different between two groups of subjects, effectively canceling each other out. Despite comparable behavioral performance on both cues and targets, one group (n = 4) elicited a fronto-central-parietal positivity, starting 500 ms postcue over frontal and prefrontal areas, later including more central and posterior scalp sites, whereas another group (n = 8) started 400 ms postcue over central sites with a negativity, growing in strength over time and stabilizing over fronto-central sites. Only the group of eight subjects showed some evidence of occipital pretarget biasing activity. Independent of group, source modeling of the attentional control activity showed that attentional control was initiated in anterior, not posterior, parts of the brain. Furthermore, different underlying sources were found for both groups, in addition to signs of differential processing of target stimuli. Possible individual differences in attentional control ability and its relation to usage of different brain areas to deal with the task demands are discussed in more detail.

The effects of selective attention on the neural response to the violation of musical syntax were investigated in the present study. Musical chord progressions were played to nonmusicians while Event-Related Potentials (ERPs) were recorded. The five-chord progressions included 61% harmonically expected cadences (I-I(6)-IV-V-I), 26% harmonically unexpected cadences (I-I(6)-IV-V-N(6)), and 13% with one of the five chords having an intensity fadeout across its duration. During the attended condition, subjects responded by pressing a button upon detecting a fadeout in volume; during the unattended condition, subjects were given reading comprehension materials and instructed to ignore all auditory stimuli. In response to the harmonic deviant, an Early Anterior Negativity (EAN) was observed at 150-300 ms in both attention conditions, but it was much larger in amplitude in the attended condition. A second scalp-negative deflection was also identified at 380-600 ms following the harmonic deviants; this Late Negativity onset earlier during the attended condition. These results suggest strong effects of attention on the neural processing of harmonic syntax.