Investigating cortico-subcortical circuits during auditory sensory attenuation: A combined magnetoencephalographic and dynamic causal modeling study

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

Altered autonomic function in individuals at clinical high risk for psychosis

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

Association of Magnetoencephalographically Measured High-Frequency Oscillations in Visual Cortex With Circuit Dysfunctions in Local and Large-scale Networks During Emerging Psychosis

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

Thalamo-cortical circuits during sensory attenuation in emerging psychosis: a combined magnetoencephalography and dynamic causal modelling study

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

Visual search performance is predicted by both prestimulus and poststimulus electrical brain activity

© The Author(s) 2016. An individual's performance on cognitive and perceptual tasks varies considerably across time and circumstances. We investigated neural mechanisms underlying such performance variability using regression-based analyses to examine trial-by-trial relationships between response times (RTs) and different facets of electrical brain activity. Thirteen participants trained five days on a color-popout visual-search task, with EEG recorded on days one and five. The task was to find a color-popout target ellipse in a briefly presented array of ellipses and discriminate its orientation. Later within a session, better preparatory attention (reflected by less prestimulus Alpha-band oscillatory activity) and better poststimulus early visual responses (reflected by larger sensory N1 waves) correlated with faster RTs. However, N1 amplitudes decreased by half throughout each session, suggesting adoption of a more efficient search strategy within a session. Additionally, fast RTs were preceded by earlier and larger lateralized N2pc waves, reflecting faster and stronger attentional orienting to the targets. Finally, SPCN waves associated with target-orientation discrimination were smaller for fast RTs in the first but not the fifth session, suggesting optimization with practice. Collectively, these results delineate variations in visual search processes that change over an experimental session, while also pointing to cortical mechanisms underlying performance in visual search

Oscillatory neural signatures of visual perception across developmental stages in individuals with 22q11.2 deletion syndrome

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

Intact mismatch negativity responses in clinical high-risk for psychosis and first-episode psychosis: evidence from source-reconstructed event-related fields and time-frequency data

Background: To examine whether Mismatch Negativity (MMN) Responses are impaired in participants at clinical high-risk for psychosis (CHR-P) and first episode psychosis (FEP) patients and whether MMN-deficits predict clinical outcomes in CHR-Ps. Methods: Magnetoencephalography (MEG) data were collected during a duration-deviant MMN-paradigm for a group of 116 CHR-P participants, 33 FEP patients, (15 antipsychotic-naïve), a psychosis-risk-negative group (CHR-N: n=38) with substance abuse and affective disorder and 49 healthy controls (HC). Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and inter-trial-phase-coherence (ITPC) focused on bilateral Heschl’s gyri and superior temporal gyri. Results: Significant MMNm responses were found across participants in bilateral Heschl’s gyrus and superior temporal gyri. However, MMN-amplitude as well as time-frequency and ITPC-responses were intact in CHR-P and FEP-patients relative to HC. Furthermore, MMN-deficits were not related to persistent attenuated psychotic symptoms nor transitions to psychosis in CHR-Ps. Conclusions: Our data suggest that MMNm responses in MEG-data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants

Thalamo-cortical circuits during sensory attenuation in emerging psychosis: a combined magnetoencephalography and dynamic causal modelling study

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

Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia

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

Stay Tuned: What Is Special About Not Shifting Attention?

Background: When studying attentional orienting processes, brain activity elicited by symbolic cue is usually compared to a neutral condition in which no information is provided about the upcoming target location. It is generally assumed that when a neutral cue is provided, participants do not shift their attention. The present study sought to validate this assumption. We further investigated whether anticipated task demands had an impact on brain activity related to processing symbolic cues. Methodology/Principal Findings: Two experiments were conducted, during which event-related potentials were elicited by symbolic cues that instructed participants to shift their attention to a particular location on a computer screen. In Experiment 1, attention shift-inducing cues were compared to non-informative cues, while in both conditions participants were required to detect target stimuli that were subsequently presented at peripheral locations. In Experiment 2, a non-ambiguous "stay-central'' cue that explicitly required participants not to shift their attention was used instead. In the latter case, target stimuli that followed a stay-central cue were also presented at a central location. Both experiments revealed enlarged early latency contralateral ERP components to shift-inducing cues compared to those elicited by either non-informative (exp. 1) or stay-central cues (exp. 2). In addition, cueing effects were modulated by the anticipated difficulty of the upcoming target, particularly so in Experiment 2. A positive difference, predominantly over the posterior contralateral scalp areas, could be observed for stay-central cues, especially for those predicting that the upcoming target would be easy. This effect was not present for non-informative cues. Conclusions/Significance: We interpret our result in terms of a more rapid engagement of attention occurring in the presence of a more predictive instruction (i.e. stay-central easy target). Our results indicate that the human brain is capable of very rapidly identifying the difference between different types of instructions