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Background: \ud 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.\ud \ud Methods: \ud 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.\ud \ud Results: \ud 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).\ud \ud Conclusions: \ud 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.

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-naive), 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.

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., We examined auditory sensory attenuation using a combination of magnetoencephalography (MEG) and computational modeling. 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 sensorimotor systems.

Highlights • Long Range Temporal Correlations do not reflect the clinical trajectory of psychosis. • Reduced Long Range Temporal Correlations may appear at the onset of psychosis. • Antipsychotic medication may affect Long Range Temporal Correlations. • Long Range Temporal Correlations do not correlate with symptoms of psychosis., 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.

ObjectiveTo examine whether 40-Hz Auditory Steady-State Responses (ASSR) in participants at clinical high-risk for psychosis predict clinical outcomes.MethodIn this study, magnetoencephalography (MEG) data were collected during a 40-Hz ASSR paradigm in 116 participants meeting clinical high-risk (CHR-P) for psychosis criteria, a clinical control group characterized by affective disorders and/or substance abuse (CHR-N: n=38), 32 first-episode psychosis patients (FEP, 14 antipsychotic-naïve), and 49 healthy controls. We examined 40-Hz-ASSR-source-activity in bilateral Heschl’s gyrus, superior temporal gyrus, Rolandic operculum, and the thalamus. Group differences in ASSR amplitudes were tested and correlated with neuropsychological scores, psychosocial functioning, and clinical symptoms. Linear discriminant analyses was used to assess whether 40-Hz-ASSR predicts transition to psychosis and persistence of APS.ResultsCompared to controls, 40-Hz-ASSR responses in CHR-Ps were impaired in right Rolandic operculum (d=0.41) and right thalamus (d=0.43), particularly in those with combined UHR/BS symptoms and CHR-Ps who transitioned to psychosis (n=11). FEP-patients showed significant impairments in the right thalamus (d=0.58), while the CHR-N group was unaffected. Importantly, right thalamus 40-Hz-ASSRs predicted transition to psychosis (transitioned [n=11] vs non-transitioned [n=105]); classification accuracy 73.3%, AUC=0.827), whereas this was not the case for persistent APS (Persistent [n=41] vs non-Persistent [n=37]; classification accuracy 56.4%).ConclusionsThe current study indicates that MEG-recorded 40-Hz-ASSRs constitute a potential biomarker for predicting transition to psychosis in CHR-P participants.

Magnetoencephalography (MEG) is a neuroimaging technique that has excellent temporal as well as good spatial resolution to measure neural activity. MEG, however, has only fairly recently been applied towards investigations of circuit anomalies in schizophrenia (ScZ). This chapter will summarize recent work with MEG that has examined alterations of event-related fields (ERF) and neural oscillations in task-related paradigms and during rest. We will provide an overview of the current findings as well as suggest recommendations for future research.

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.

NMDA receptor deficits have been implicated in schizophrenia. Grent-’t-Jong et al. show that treating healthy controls with ketamine triggers changes in neural oscillations during visual processing distinct from those seen in patients with schizophrenia. This suggests that acute NMDA receptor hypofunction does not account for visuo-perceptual deficits in the disorder., 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.

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. Copyright Grent-’t-Jong et al. This article is distributed under the terms of the Creative Commons Attribution License

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.

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. (c) 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.

Background Robust impairments in the power and phase of 40 Hz auditory steady state responses (ASSR) have been reported in chronic schizophrenia patients. This could reflect changes in the balance between inhibitory GABAergic and excitatory glutamatergic neurotransmission in auditory cortex. However, the direct link between the ASSR and alterations in these neurotransmitter systems has not been systematically explored. Furthermore, it remains unclear whether 40 Hz ASSR impairments are present in early and at-risk stages of psychosis. The current study aims to explore the 40 Hz ASSR in first-episode of psychosis patients and individuals at clinical high risk (CHR) of psychosis, and the possible relationship of deficits in gamma-band entrainment to a dysfunctional excitation inhibition balance, as reflected by alterations in cortical GABA and glutamate. Methods Data from 80 CHR, 11 FEP and 40 age-matched healthy control participants were collected as part of the MRC-funded Youth Mental Health Risk and Resilience study. MEG data were recorded on a 4D Neuroimaging Magnes 3600 Whole Head 248 Channel system, while participants were passively presented with a series of 1000 Hz carrier tones amplitude modulated at 40 Hz. Data were analysed at sensor and source-level in the frequency-domain for spectral power and intertrial phase-coherence (ITPC). For source-reconstruction, an eLoreta source-analysis algorithms was employed. Auditory regions of interest (ROIs) were defined using 98 nodes defined from the AAL-atlas. Levels of right auditory GABA and Glx (glutamate + glutamine) were measured using 1H-MRS at 3T and 2*2*2 cm voxels and were estimated relative to water. GABA levels were further corrected for grey and white matter and cerebrospinal fluid levels within the voxel. Finally, 40 Hz ASSR power in right auditory cortex was explored in relation to neurotransmitter levels in the same region. Results Across groups, the ASSR stimulus activated temporal regions, including bilateral heschl’s gyrus and superior temporal cortex. A significant effect of hemisphere was found, reflecting higher 40 Hz ASSR power in the right hemisphere across groups. CHR and FEP participants showed attenuated 40 Hz ASSR power and ITPC compared to healthy control participants in right temporal regions, but an increase in spectral power in the left hemisphere. A moderate positive correlation was found between right auditory GABA and 40 Hz ASSR power in the right superior temporal gyrus in CHR, but not in controls. Discussion These results provide a link between MRS measures of GABA and 40 Hz ASSR power impairments in CHR individuals. Furthermore, these preliminary findings indicate that slight alterations in the 40 Hz ASSR are present in FEP patients and may arise already in the CHR stage, prior to the onset of psychosis.

Background The ability to predict the sensory feedback of self-generated stimuli against incoming sensory information is of importance to distinguish internal from external stimuli and is associated with sensory attenuation. Furthermore, it has been proposed that deficits in sensory attenuation could contribute to clinical symptoms of schizophrenia, including hallucinations and delusions, involving potential deficits in corollary discharge. The current study examined the hypothesis whether sensory attenuation is present in participants at clinical high–risk (CHR) for psychosis. Methods Sixty-four CHR-participants and 32 healthy controls were presented with auditory stimuli during two experimental conditions: 1) In a passive condition, participants were presented with ripple sounds (40HZ with 2000ms duration, 83db) and responded to flat sounds (1000HZ with 2000ms duration,83db) with the right-index finger and 2) In an active condition, the ripple sounds were elicited by a button press with the right-index finger every 4s. MEG-data were acquired with a 248-magnetometers whole-head MEG system (MAGNES 3600 WH, 4-D Neuroimaging) at a sampling rate of 1017Hz. We focussed on the M100 response during the passive and active conditions at sensor- and source-level. A LCMV beamforming approach was employed for source reconstruction and virtual channels in primary auditory cortex and the left superior temporal cortex were used further analysis of sensory attenuation effects. Condition and group effects were tested with a cluster-based nonparametric test implemented in Fieldtrip with a window of interest for the M100 component between 120ms-150ms. Results There was a significant decrease (P =0.009) in the amplitude of M100 component in the active vs. passive conditions across groups at both sensor- and source-level. Interaction-effects revealed that that sensory attenuation was significantly reduced in auditory cortices in the CHR group vs controls (P=0.032). Discussion The current results highlight that sensory attenuation can be studied with ASSR-paradigms and that both primary auditory and superior temporal cortices underlie this effect. Moreover, our current findings suggest that sensory attenuation is impaired in CHR-participants, suggesting the possibility of impaired corollary discharge processes as a potential biomarker for the early diagnosis and detection of schizophrenia.

Background Auditory mismatch negativity (MMN) and its magnetic counterpart (MMNm) are event-related potentials/fields elicited by violations of previously established auditory regularities (Näätänen et al. 2007). Reduced MMN amplitude is a robust finding in both medicated and unmedicated schizophrenia (ScZ) patients (for a review, see Umbricht & Krljes, 2005), potentially indicating impaired predictive processes (Sauer et al. 2017). Furthermore, several studies have examined MMN responses in individuals at clinical high risk for psychosis (CHR) and have found MMN deficits to be present already in this population, indicating that MMN is compromised before psychosis onset and could represent a marker of risk for psychosis development. However, not all studies have reported significant differences in MMN amplitude between clinical high risk and healthy individuals and there is evidence to suggest that MMN deficits are primarily observed in CHR individuals who transition to psychosis (Bodatsch et al., 2015). Methods The purpose of the present study is to investigate MEG recorded MMNm amplitude responses to both duration deviants and sound omissions in n = 90 CHR-individuals who were screened with the Schizophrenia Proneness Instrument and the Comprehensive Assessment of At Risk Mental States. N = 50 healthy controls served as a comparison group. We employed an auditory oddball paradigm in which three different sequences of auditory stimuli were presented binaurally at ~ 70 dB (150 ms SOA, 700 – 100 ms ISI). The standard sequence contained five identical tones (80 ms) and the deviant sequence contained four identical tones and one duration deviant tone (40 ms). In addition, an omission sequence which contained only four identical tones was included to examine auditory predictions. Participants were instructed to focus their attention away from the sounds and to perform a simple visual detection task. We analyzed MMNm responses to unpredictable deviant and omitted sounds in bsensor and source space. The linearly constrained minimum variance (LCMV) beamformer was used to identify the generators of the MMNm responses and to compute artefact-free source-level time-courses. Results Consistent with previous studies revealing MMN sources in auditory cortical areas, bilateral MMNm sources were localized in auditory cortices for both duration deviants and sound omissions. Our data show attenuated MMNm responses elicited by duration deviant sounds in CHR individuals compared to healthy controls. Discussion Taken together, the study findings suggest that reduced MMNm amplitude is present before psychosis onset and reflects aberrant predictive processing rather than deficient stimulus-specific adaptation. Clinical follow-up measurements will be obtained to determine whether MMNm amplitudes are a potential biomarker for predicting onset of psychosis.

The pathophysiology of schizophrenia may fundamentally involve a disturbance in the interaction between neuronal groups that leads to impaired communication within and between brain areas. Such a “dysconnectivity syndrome” could underlie the pronounced cognitive deficits as well as the emergence of psychosis. Evidence for this hypothesis has mainly come from functional magnetic resonance imaging (fMRI) studies which have investigated connectivity anomalies during spontaneous as well as task-related activity. In the current review, we will summarize evidence from electro- and magnetoencephalography (EEG/MEG) which have employed measures, such as coherence, phase-locking and mutual information, that have tested changes in functional connectivity during task-related as well as resting-state time-frequency data. We will highlight the methodological issues associated with these measures as well as provide recommendations for future research.

Background:\ud \ud Gamma-band oscillations are prominently impaired in schizophrenia, but the nature of the deficit and relationship to perceptual processes is unclear.\ud \ud Methods:\ud \ud 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 (1–100 Hz) 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.\ud \ud Results:\ud \ud 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.\ud \ud Conclusions:\ud \ud 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.

The integration of multisensory information has been shown to be guided by spatial and temporal proximity, as well as to be influenced by attention. Here we used neural measures of the multisensory spread of attention to investigate the spatial and temporal linking of synchronous versus near-synchronous auditory and visual events. Human participants attended selectively to one of two lateralized visual-stimulus streams while task-irrelevant tones were presented centrally. Electrophysiological measures of brain activity showed that tones occurring simultaneously or delayed by 100 ms were temporally linked to an attended visual stimulus, as reflected by robust cross-modal spreading-of-attention activity, but not when delayed by 300 ms. The neural data also indicated a ventriloquist-like spatial linking of the auditory to the attended visual stimuli, but only when occurring simultaneously. These neurophysiological results thus provide unique insight into the temporal and spatial principles of multisensory feature integration and the fundamental role attention plays in such integration.

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.

Previously, we have shown that spatial attention to a visual stimulus can spread across both space and modality to a synchronously presented but task-irrelevant sound arising from a different location, reflected by a late-onsetting, sustained, negative-polarity event-related potential (ERP) wave over fronto-central scalp sites, likely originating in part from the auditory cortices. Here we explore the influence of cross-modal conflict on the amplitude and temporal dynamics of this multisensory spreading-of-attention activity. Subjects attended selectively to one of two concurrently presented lateral visual-letter streams to perform a sequential comparison task, while ignoring task-irrelevant, centrally presented spoken letters that could occur synchronously with either the attended or unattended lateral visual letters and could be either congruent or incongruent with them. Extracted auditory ERPs revealed that, collapsed across congruency, attentional spreading across modalities started around 220 ms, replicating our earlier findings. The interaction between attentional spreading and conflict occurred beginning at around 300 ms, with attentional-spreading activity being larger for incongruent trials. Thus, the increased processing of an incongruent, task-irrelevant sound in a multisensory stimulation appear to occur some time after attention has spread from the attended visual part to the ignored auditory part, presumably reflecting that the conflict detection and associated attentional capture occurs after the accrual of some multisensory interaction processes at a higher-level semantic processing stage.

Background Hypofunction of the N-methyl-D-aspartate receptor (NMDA-R) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia (ScZ). Methods In a single-blind cross-over design, 14 participants received either a subanaesthetic dose of S-ketamine (0.006 mg/Kg) or saline while Magnetoencephalographic (MEG) data were recorded during a visual task. In addition, MEG-data were obtained in a sample of unmedicated first-episode psychosis (FEP) patients (n = 10) and in patients with chronic ScZ (n = 16). MEG-data were analyzed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest (ROIs). In addition, directed functional connectivity analysis was performed using Granger Causality (GC). Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Results Behavioral impairments were accompanied by increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions during Ketamine administration, while low-frequency (~5–30 Hz) activity was upregulated. Moreover, Ketamine disrupted feedforward (FF) and feedback (FB) signaling at high and low frequencies leading to hypoconnectivity in thalamo-cortical (TC) networks. In contrast, FEP and chronic ScZ patients showed a different pattern of MEG-activity, characterized by decreased task-induced high-gamma band oscillations and increased FF/FB-mediated GC-connectivity. Discussion The effects of Ketamine on high-frequency oscillations and their connectivity profile are not consistent with observations in FEP and chronic ScZ-patients. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that the effects of acute NMDA-R hypofunction are not consistent with impairments in visuo-perceptual oscillations in ScZ-patients.

Moderate doses of alcohol (blood alcohol concentration [BAC] of about 0.05%) may result in acute impairments at various levels of information processing. A number of reports have documented detrimental effects of moderate alcohol on the mismatch negativity (MMN), the electrocortical manifestation of a rapid (100 ms poststimulus) mechanism dedicated to the detection of unexpected auditory change (e.g., Jääskeläinen, et al., 1995). Recently, we and others identified a partial visual counterpart of the MMN, sometimes called the rareness-related negativitity (RRN). Analogous to the MMN, the RRN evolves at about 100 ms after the unexpected change and was localized in visual cortex (Kenemans, et al., 2003). Rapid detection of unexpected events is important for everyday-life conditions like driving, prompting the question whether the visual RRN shows sensitivity to moderate alcohol similar to the MMN. In all, 16 subjects were tested either under moderate alcohol or under placebo. Unexpected visual change was implemented by presenting 2.4 versus 0.6 c/d gratings in pseudorandom sequences according to a deviant (10%)/standard (90%) schedule. The alcohol effects on MMN reported before were replicated. Furthermore, the RRN, defined as the difference between deviant and standard event-related potentials between 120 and 170 ms at Oz, was present under placebo but not under alcohol. It is concluded that moderate alcohol does indeed impair the rapid detection in visual cortex of unexpected changes. In contrast, electrocortical correlates of lower level sensory processing were still significantly present under alcohol.

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.

How do we detect changes in our visual environment? By continuously comparing visual inputs to templates of experiences in the immediate past? Or by determining their rareness, how infrequently a visual event occurred previously? Recent results from event-related potentials have been interpreted in favour of the first hypothesis, as in the case of the auditory mismatch negativity. Here we demonstrate that rareness, rather than mismatch with a template, underlies visual change detection. Such rareness is detected through a dedicated mechanism in human visual cortex about 100 ms after the rare event occurs, reflected in the rareness-related negativity (RRN).

Contains fulltext : 147443.pdf (Publisher’s version ) (Open Access) UNLABELLED: Ethologically inspired models of movement preparation view the sensorimotor system as sampling information from the environment in a parallel fashion in preparation for multiple potential actions. In support, the configuration of the physical workspace, manipulated by the number or spatial separation of potential targets, has been shown to modulate sensorimotor neural activity. It is unclear, however, whether this modulation is driven by the sensory layout of the workspace or through the associated motor plans. Here, we combine a delayed-movement pre-cuing task with visuomotor adaptation to address this question in human subjects while recording MEG. By dissociating visual and motor coordinates of two targets using visuomotor adaptation, the task was designed to evaluate, in a selective fashion, the effects of visual and movement target separation on movement preparatory activity. The results did not allow the intended comparison due to an unanticipated effect of the direction of visuomotor adaptation on baseline oscillatory power in beta and low-gamma bands. Fortuitously, this effect was dependent on whether the adaptation direction decreased or increased the angular separation between alternative movements. That is, there was a sustained reduction of oscillatory power, which was stronger at small compared with large target separation. These results support a direct influence of movement target separation on motor cortex neural activity, mediated by lateral interactions between simultaneously active motor plans. The results further demonstrate a novel effect of visuomotor adaptation on motor cortex oscillatory activity, with properties that support the local nature of learned changes in visuomotor mapping. SIGNIFICANCE STATEMENT: There is growing evidence that the motor cortex routinely prepares for different movements simultaneously, each suited to a possible course of events in the immediate environment. The preparatory motor cortex activity for different movements can be seen as a competition between groups of neurons. This competition is influenced by how similar the alternative movements are; for example, in terms of direction, determined by the proximity of alternative movement goals. This study investigates whether the proximity of alternative reach goals has a direct influence on motor cortex activity (in the form of brain oscillations) or if it has an effect only through conscious evaluation of the separation between targets. We establish that there is a direct effect, supporting the biased competition model of action selection. 10 p.

Background: Auditory mismatch negativity (MMN) is an event-related potential/field elicited automatically by violations of previously established auditory regularities (Näätänen et al, 2007). MMN amplitudes have been consistently found to be attenuated in both medicated and unmedicated schizophrenia (ScZ) patients (Umbricht and Krljes, 2005), potentially indicating aberrant predictive coding processing. Moreover, recent studies have found MMN deficits to be present already in individuals at ultra-high risk (UHR) for psychosis, indicating that MMN is compromised before psychosis onset and could represent a marker of risk for psychosis development.

Contains fulltext : 130558.pdf (Publisher’s version ) (Open Access) 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 degrees ). 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 degrees 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. 9 p.

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 (∼400 versus ∼700 ms). This was then followed (∼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., Author Summary Attention is a fundamental cognitive function that allows us to focus neural resources on events or information in our environment that are most important or interesting to us at any given moment. Recent functional neuroimaging studies have indicated that a network of brain areas in frontal and parietal cortex is involved in directing our attention to specific locations in our visual field. However, little is known about the timing and sequence of activations within the various parts of this attentional control network, thus limiting our understanding of their functional roles. We extracted a more precise picture of the neural mechanisms of attentional control by combining two complementary methods of measuring cognitive brain activity: functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). fMRI offers information on a millimeter scale about the locations of brain activity, whereas EEG offers temporal information on a scale of milliseconds. Our results indicate that visual-spatial attentional control is initiated in frontal brain areas, joined shortly afterwards by parietal involvement. Together, these brain areas then prepare relevant areas in the visual cortex for performing enhanced processing of visual input in the attended region of space., A combination of methods reveals the timing and sequence of neural activation within the frontal-parietal network and provides a more precise picture of the mechanisms controlling visual attention in humans.

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.

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. D 2005 Elsevier B.V. All rights reserved. Theme: Neural basis of behavior Topic: Cognition