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.

Towards a neurodynamical understanding of the prodrome in schizophrenia.

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.

Low-Frequency Oscillatory Correlates of Auditory Predictive Processing in Cortical-Subcortical Networks: A MEG-Study.

Emerging evidence supports the role of neural oscillations as a mechanism for predictive information processing across large-scale networks. However, the oscillatory signatures underlying auditory mismatch detection and information flow between brain regions remain unclear. To address this issue, we examined the contribution of oscillatory activity at theta/alpha-bands (4-8/8-13 Hz) and assessed directed connectivity in magnetoencephalographic data while 17 human participants were presented with sound sequences containing predictable repetitions and order manipulations that elicited prediction-error responses. We characterized the spectro-temporal properties of neural generators using a minimum-norm approach and assessed directed connectivity using Granger Causality analysis. Mismatching sequences elicited increased theta power and phase-locking in auditory, hippocampal and prefrontal cortices, suggesting that theta-band oscillations underlie prediction-error generation in cortical-subcortical networks. Furthermore, enhanced feedforward theta/alpha-band connectivity was observed in auditory-prefrontal networks during mismatching sequences, while increased feedback connectivity in the alpha-band was observed between hippocampus and auditory regions during predictable sounds. Our findings highlight the involvement of hippocampal theta/alpha-band oscillations towards auditory prediction-error generation and suggest a spectral dissociation between inter-areal feedforward vs. feedback signalling, thus providing novel insights into the oscillatory mechanisms underlying auditory predictive processing.

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields.

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.

Test-retest reliability of the magnetic mismatch negativity response to sound duration and omission deviants.

Mismatch negativity (MMN) is a neurophysiological measure of auditory novelty detection that could serve as a translational biomarker of psychiatric disorders, such as schizophrenia. However, the replicability of its magnetoencephalographic (MEG) counterpart (MMNm) has been insufficiently addressed. In the current study, test-retest reliability of the MMNm response to both duration and omission deviants was evaluated over two MEG sessions in 16 healthy adults. MMNm amplitudes and latencies were obtained at both sensor- and source-level using a cortically-constrained minimum-norm approach. Intraclass correlations (ICC) were derived to assess stability of MEG responses over time. In addition, signal-to-noise ratios (SNR) and within-subject statistics were obtained in order to determine MMNm detectability in individual participants. ICC revealed robust values at both sensor- and source-level for both duration and omission MMNm amplitudes (ICC = 0.81-0.90), in particular in the right hemisphere, while moderate to strong values were obtained for duration MMNm and omission MMNm peak latencies (ICC = 0.74-0.88). Duration MMNm was robustly identified in individual participants with high SNR, whereas omission MMNm responses were only observed in half of the participants. Our data indicate that MMNm to unexpected duration changes and omitted sounds are highly reproducible, providing support for the use of MEG-parameters in basic and clinical research.

The 40-Hz Auditory Steady-State Response in Patients With Schizophrenia: A Meta-analysis.

IMPORTANCE: The neurobiological mechanisms underlying circuit dysfunctions in schizophrenia remain poorly understood. The 40-Hz auditory steady-state response (ASSR) has been suggested as a potential biomarker for schizophrenia. OBJECTIVES: To provide a meta-analytical insight into the presence of 40-Hz ASSR impairments in patients with schizophrenia and to examine the effects of the participant group, stimulus parameters, and analysis and recording techniques. DATA SOURCES: Searches were conducted in PubMed and reference lists of appropriate publications to identify relevant studies published from November 1999 to March 2016. Initial literature searches were performed with combinations of the following search terms: (1) auditory steady state response, (2) schizophrenia, (3) 40 Hz, (4) EEG, (5) MEG, and (6) steady state response. STUDY SELECTION: Original articles reporting 40-Hz ASSR data on patients with schizophrenia (chronic or first episode) compared with healthy controls using electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings. DATA EXTRACTION AND SYNTHESIS: Hedges g effect sizes were calculated using sample sizes, P values, and/or Cohen d effect sizes from 20 studies. Effect size data were pooled using random-effects models. Publication bias was corrected for using funnel plots, the Egger regression test, and a trim and fill test. The contributions of study design parameters and participant characteristics were assessed using a mixed linear model approach and subsequent post hoc t tests. The present analysis was performed during the period from November 2015 to March 2016. MAIN OUTCOMES AND MEASURES: Random model Hedges g effect sizes for auditory steady-state amplitude and phase-locking measures from sensor/electrode and sources-space responses in EEG and MEG studies. RESULTS: Of the 20 studies analyzed (representing a total of 590 healthy controls and 606 patients with schizophrenia), 17 reported significant reductions in 40-Hz ASSR spectral power and/or phase locking in patients with schizophrenia compared with healthy controls (Hedges g effect: -0.58 [power] and -0.46 [phase]). Effect sizes from spectral power and phase-locking measures did not differ significantly (95% CI, -0.49 to 0.22; t = -0.80; P = .43). Stimulus characteristics and analysis methods were not associated with the findings of 40-Hz ASSR impairment in schizophrenia. CONCLUSIONS AND RELEVANCE: The 40-Hz ASSR spectral power and phase-locking deficits are robust in schizophrenia, which suggests that these measures could be useful probes for assessing circuit dysfunctions in the disorder. Moreover, these findings should motivate large-scale studies of the longitudinal expression in patients with schizophrenia and at-risk populations, to further validate the 40-Hz ASSR as a potential biomarker.

Repetition suppression and repetition enhancement underlie auditory memory-trace formation in the human brain: an MEG study.

The formation of echoic memory traces has traditionally been inferred from the enhanced responses to its deviations. The mismatch negativity (MMN), an auditory event-related potential (ERP) elicited between 100 and 250ms after sound deviation is an indirect index of regularity encoding that reflects a memory-based comparison process. Recently, repetition positivity (RP) has been described as a candidate ERP correlate of direct memory trace formation. RP consists of repetition suppression and enhancement effects occurring in different auditory components between 50 and 250ms after sound onset. However, the neuronal generators engaged in the encoding of repeated stimulus features have received little interest. This study intends to investigate the neuronal sources underlying the formation and strengthening of new memory traces by employing a roving-standard paradigm, where trains of different frequencies and different lengths are presented randomly. Source generators of repetition enhanced (RE) and suppressed (RS) activity were modeled using magnetoencephalography (MEG) in healthy subjects. Our results show that, in line with RP findings, N1m (~95-150ms) activity is suppressed with stimulus repetition. In addition, we observed the emergence of a sustained field (~230-270ms) that showed RE. Source analysis revealed neuronal generators of RS and RE located in both auditory and non-auditory areas, like the medial parietal cortex and frontal areas. The different timing and location of neural generators involved in RS and RE points to the existence of functionally separated mechanisms devoted to acoustic memory-trace formation in different auditory processing stages of the human brain.

Encoding of nested levels of acoustic regularity in hierarchically organized areas of the human auditory cortex.

Our auditory system is able to encode acoustic regularity of growing levels of complexity to model and predict incoming events. Recent evidence suggests that early indices of deviance detection in the time range of the middle-latency responses (MLR) precede the mismatch negativity (MMN), a well-established error response associated with deviance detection. While studies suggest that only the MMN, but not early deviance-related MLR, underlie complex regularity levels, it is not clear whether these two mechanisms interplay during scene analysis by encoding nested levels of acoustic regularity, and whether neuronal sources underlying local and global deviations are hierarchically organized. We registered magnetoencephalographic evoked fields to rapidly presented four-tone local sequences containing a frequency change. Temporally integrated local events, in turn, defined global regularities, which were infrequently violated by a tone repetition. A global magnetic mismatch negativity (MMNm) was obtained at 140-220 ms when breaking the global regularity, but no deviance-related effects were shown in early latencies. Conversely, Nbm (45-55 ms) and Pbm (60-75 ms) deflections of the MLR, and an earlier MMNm response at 120-160 ms, responded to local violations. Distinct neuronal generators in the auditory cortex underlay the processing of local and global regularity violations, suggesting that nested levels of complexity of auditory object representations are represented in separated cortical areas. Our results suggest that the different processing stages and anatomical areas involved in the encoding of auditory representations, and the subsequent detection of its violations, are hierarchically organized in the human auditory cortex.

Two sequential processes of change detection in hierarchically ordered areas of the human auditory cortex.

Auditory deviance detection occurs around 150 ms after the onset of a deviant sound. Recent studies in animals and humans have described change-related processes occurring during the first 50 ms after sound onset. However, it still remains an open question whether these early and late processes of deviance detection are organized hierarchically in the human auditory cortex. We applied a beamforming source reconstruction approach in order to estimate brain sources associated with 2 temporally distinct markers of deviance detection. Results showed that rare frequency changes elicit an enhancement of the Nbm component of the middle latency response (MLR) peaking at 43 ms, in addition to the magnetic mismatch negativity (MMNm) peaking at 115 ms. Sources of MMNm, located in the right superior temporal gyrus, were lateral and posterior to the deviance-related MLR activity being generated in the right primary auditory cortex. Source reconstruction analyses revealed that detection of changes in the acoustic environment is a process accomplished in 2 different time ranges, by spatially separated auditory regions. Paralleling animal studies, our findings suggest that primary and secondary areas are involved in successive stages of deviance detection and support the existence of a hierarchical network devoted to auditory change detection.

Electrophysiological index of acoustic temporal regularity violation in the middle latency range.

OBJECTIVE: Acoustic violations in temporal regularity have been traditionally indexed by mismatch negativity (MMN). However, recent studies have demonstrated that humans can detect auditory changes in physical sound features, such as frequency, location and intensity, in the first 50 ms after sound onset. Our aim was to examine if temporal regularity violations could be detected in the middle latency range. METHODS: We used an oddball paradigm with 290 ms as standard stimulus onset asynchrony (SOA) and 200 ms as deviant SOA. We also employed a control paradigm that comprised of seven SOAs including 200 and 290 ms, in order to control for differences due to refractoriness. RESULTS: In the middle latency range, temporal regularity violations led to enhanced Pa and Nb responses, which behaved differently to the corresponding SOAs in the control condition. In the long latency range, temporal regularity violations led to similar behaviours in both oddball and control paradigms. CONCLUSIONS: These findings suggest that with a fast presentation rate, human brains are capable to detect temporal regularity violations in the middle latency range. SIGNIFICANCE: Together with previous studies that found early change detection responses, the current study emphasises that the human brain can encode simple regularity violation as early as approximately 50 ms post-stimulus onset.

Ultrafast tracking of sound location changes as revealed by human auditory evoked potentials.

The rapid discrimination of auditory location information enables grouping and selectively attending to specific sound sources. The typical indicator of auditory change detection is the mismatch negativity (MMN) occurring at a latency of about 100-250 ms. However, recent studies have revealed the existence of earlier markers of frequency deviance detection in the middle-latency response (MLR). Here, we measured the MLR and MMN to changes in sound location. Clicks were presented in either the left or right hemifields during oddball (rare 30°-shifts in location), reversed oddball, and control (sounds occurring equiprobably from five locations) conditions. Clicks at deviant locations elicited an MMN and an enhanced Na component of the MLR peaking at 20 ms compared to clicks at standard or control locations. Whereas MMN was not significantly lateralized, the Na effect showed a contralateral dominance. These findings indicate that, also for sound location changes, early detection processes exist upstream of MMN.