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Neural oscillations are fundamental mechanisms of the human brain that enable coordinated activity of different brain regions during perceptual and cognitive processes. A frontotemporal network generated by means of gamma oscillations and comprising the auditory cortex (AC) and the anterior cingulate cortex (ACC) has been shown to be involved in the cognitively demanding auditory information processing. This study aims to reveal patterns of functional and effective connectivity within this network in healthy subjects by means of simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We simultaneously recorded EEG and fMRI in 28 healthy subjects during the performance of a cognitively demanding auditory choice reaction task. Connectivity between the ACC and AC was analysed employing EEG and fMRI connectivity measures. We found a significant BOLD signal correlation between the ACC and AC, a significant task-dependant increase of fMRI connectivity (gPPI) and a significant increase in functional coupling in the gamma frequency range between these regions (LPS), which was increased in top-down direction (granger analysis). EEG and fMRI connectivity measures were positively correlated. The results of these study point to a role of a top-down influence of the ACC on the AC executed by means of gamma synchronisation. The replication of fMRI connectivity patterns in simultaneously recorded EEG data and the correlation between connectivity measures from both domains found in our study show, that brain connectivity based on the synchronisation of gamma oscillations is mirrored in fMRI connectivity patterns., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Synchronized oscillatory gamma-band activity (30-100Hz) has been suggested to constitute a key mechanism to dynamically orchestrate sensory information integration across multiple spatio-temporal scales. We here tested whether interhemispheric functional connectivity and ensuing auditory perception can selectively be modulated by high-density transcranial alternating current stimulation (HD-tACS). For this purpose, we applied multi-site HD-tACS at 40Hz bilaterally with a phase lag of 180° and recorded a 64-channel EEG to study the oscillatory phase dynamics at the source-space level during a dichotic listening (DL) task in twenty-six healthy participants. In this study, we revealed an oscillatory phase signature at 40Hz which reflects different temporal profiles of the phase asymmetries during left and right ear percept. Here we report that 180°-tACS did not affect the right ear advantage during DL at group level. However, a follow-up analysis revealed that the intrinsic phase asymmetries during sham-tACS determined the directionality of the behavioral modulations: While a shift to left ear percept was associated with augmented interhemispheric asymmetry (closer to 180°), a shift to right ear processing was elicited in subjects with lower asymmetry (closer to 0°). Crucially, the modulation of the interhemispheric network dynamics depended on the deviation of the tACS-induced phase-lag from the intrinsic phase asymmetry. Our characterization of the oscillatory network trends is giving rise to the importance of phase-specific gamma-band coupling during ambiguous auditory perception, and emphasizes the necessity to address the inter-individual variability of phase asymmetries in future studies by tailored stimulation protocols., Competing Interests: The authors have declared that no competing interests exist.

Interhemispheric connectivity between auditory areas is highly relevant for normal auditory perception and alterations are a major factor for the development of auditory verbal hallucinations. Surprisingly, there is no combined EEG-DTI study directly addressing the role of functional and structural connectivity in the same group of subjects. Accordingly, nothing is known about the relationship between functional connectivity such as gamma-band synchrony, structural integrity of the interhemispheric auditory pathways (IAPs) and language lateralization as well as whether the gamma-band synchrony is configured on the backbone of IAPs. By applying multimodal imaging of 64-channel EEG and DTI tractography, we investigated in 27 healthy volunteers the functional gamma-band synchrony between either bilateral primary or secondary auditory cortices from eLORETA source-estimation during dichotic listening, as well as the correspondent IAPs from which fractional anisotropy (FA) values were extracted. Correlation and regression analyses revealed highest values for gamma-band synchrony, followed by FA for secondary auditory cortices, which were both significantly related to a reduced language lateralization. There was no such association between the white-matter microstructure and gamma-band synchrony, suggesting that structural connectivity might also be relevant for other (minor) aspects of information transfer in addition to gamma-band synchrony, which are not detected in the present coupling analyses. The combination of multimodal EEG-DTI imaging provides converging evidence of neural correlates by showing that both stronger pathways and increased gamma-band synchrony within one cohort of subjects are related to a reduced leftward-lateralization for language.

Interhemispheric auditory connectivity via the corpus callosum has been demonstrated to be important for normal speech processing. According to the callosal relay model, directed information flow from the right to the left auditory cortex has been suggested, but this has not yet been proven. For this purpose, 33 healthy participants were investigated with 64-channel EEG while performing the dichotic listening task in which two different consonant-vowel syllables were presented simultaneously to the left (LE) and right ear (RE). eLORETA source estimation was used to investigate the functional (lagged phase synchronization/LPS) and effective (isolated effective coherence/ICoh) connectivity between right and left primary (PAC) and secondary auditory cortices (SAC) in the gamma-band (30-100 Hz) during right and left ear reports. The major finding was a significantly increased effective connectivity in the gamma-band from the right to the left SAC during conscious perception of LE stimuli. In addition, effective and functional connectivity was significantly enhanced during LE as compared to RE reports. These findings give novel insight into transcallosal information transfer during auditory perception by showing that LE performance requires causal interhemispheric inputs from the right to the left auditory cortices, and that this interaction is mediated by synchronized gamma-band oscillations.

Our understanding of the neural correlates of auditory-verbal-hallucinations (AVH) has substantially increased during the last few years, but is far from sufficient. One current hypothesis, the interhemispheric miscommunication theory, is based on findings from fMRI, DTI and EEG, but there is only limited evidence so far concerning underlying functional coupling mechanisms. Here we report a 64-channel EEG study using lagged phase synchronization analysis and eLORETA source estimation to examine the functional connectivity between bilateral auditory cortices in the gamma-band in 26 schizophrenia patients (13 with and 13 without AVH) and 26 matched healthy controls (HC) while performing a dichotic listening task. We found a significantly reduced right-ear-advantage (REA) in AVH but not in non-AVH patients compared to HC. The major finding was significantly stronger gamma-band connectivity between bilateral auditory cortices during conscious perception of left (versus right) ear syllables in patients with AVH compared to HC and patients without AVH. A significant positive correlation was found between this connectivity alteration and the AVH symptom score in schizophrenia patients. These findings provide further support for the interhemispheric miscommunication hypothesis of AVH pathophysiology by indicating that aberrant gamma-band coupling between auditory cortices is related to the emergence of AVH in schizophrenia.

High frequency oscillations in the gamma range are known to be involved in early stages of auditory information processing in terms of synchronization of brain regions, e.g., in cognitive functions. It has been shown using EEG source localisation, as well as simultaneously recorded EEG-fMRI, that the auditory evoked gamma-band response (aeGBR) is modulated by attention. In addition to auditory cortex activity a dorsal anterior cingulate cortex (dACC) generator could be involved. In the present study we investigated aeGBR magnetic fields using magnetoencephalography (MEG). We aimed to localize the aeGBR sources and its connectivity features in relation to mental effort. We investigated the aeGBR magnetic fields in 13 healthy participants using a 275-channel CTF-MEG system. The experimental paradigms were two auditory choice reaction tasks with different difficulties and demands for mental effort. We performed source localization with eLORETA and calculated the aeGBR lagged phase synchronization between bilateral auditory cortices and frontal midline structures. The eLORETA analysis revealed sources of the aeGBR within bilateral auditory cortices and in frontal midline structures of the brain including the dACC. Compared to the control condition the dACC source activity was found to be significantly stronger during the performance of the cognitively demanding task. Moreover, this task involved a significantly stronger functional connectivity between auditory cortices and dACC. In accordance with previous EEG and EEG-fMRI investigations, our study confirms an aeGBR generator in the dACC by means of MEG and suggests its involvement in the effortful processing of auditory stimuli.

Objectives: The interhemispheric auditory pathway has been shown to play a crucial role in the processing of acoustic stimuli, and alterations of structural and functional connectivity between bilateral auditory areas are likely relevant to the pathogenesis of auditory verbal hallucinations (AVHs). The aim of this study was to examine this pathway in patients with chronic schizophrenia regarding their lifetime history of AVHs., Methods: DTI scans were acquired from 33 healthy controls (HC), 24 schizophrenia patients with a history of AVHs (LT-AVH) and nine schizophrenia patients without any lifetime hallucinations (N-LT-AVH). The interhemispheric auditory fibre bundles were extracted using streamline tractography. Subsequently, diffusivity indices, namely Fractional Anisotropy (FA), Trace, Mode, Axial and Radial diffusivity, were calculated., Results: FA was decreased over the entire pathway in LT-AVH compared with N-LT-AVH. Moreover, LT-AVH displayed decreased FA and Mode as well as increased radial diffusivity in the midsagittal section of the fibre tract., Conclusions: These findings indicate complex microstructural changes in the interhemispheric auditory pathway of schizophrenia patients with a history of AVHs. Alterations appear to be absent in patients who have never hallucinated.

While the role of synchronized oscillatory activity in the gamma-band frequency range for conscious perception is well established in the visual domain, there is limited evidence concerning neurophysiological mechanisms in conscious auditory perception. In the current study, we addressed this issue with 64-channel EEG and a dichotic listening (DL) task in twenty-five healthy participants. The typical finding of DL is a more frequent conscious perception of the speech syllable presented to the right ear (RE), which is attributed to the supremacy of the contralateral pathways running from the RE to the speech-dominant left hemisphere. In contrast, the left ear (LE) input initially accesses the right hemisphere and needs additional transfer via interhemispheric pathways before it is processed in the left hemisphere. Using lagged phase synchronization (LPS) analysis and eLORETA source estimation we examined the functional connectivity between right and left primary and secondary auditory cortices in the main frequency bands (delta, theta, alpha, beta, gamma) during RE/LE-reports. Interhemispheric LPS between right and left primary and secondary auditory cortices was specifically increased in the gamma-band range, when participants consciously perceived the syllable presented to the LE. Our results suggest that synchronous gamma oscillations are involved in interhemispheric transfer of auditory information., (Copyright © 2014 Elsevier Inc. All rights reserved.)

High frequency oscillations in the 40 Hz (gamma-band)-range are involved in the synchronization of brain regions, e.g., in cognitive functions. It has been suggested that the auditory evoked gamma-band response (GBR) is affected by attention and apart from auditory cortex activity a frontal or anterior cingulate cortex (ACC) generator could be involved. It was the aim of the present study to address three questions: (1) is there a neural generator of the early evoked GBR in the dorsal (d)ACC? (2) Are there different activation patterns in the dACC and the auditory cortex areas in response to task difficulty? (3) Is it possible to detect an influence of early ACC-gamma-band activity (GBR timeframe) to later auditory information processing (N1 timeframe)? In the present EEG/ERP-study we have investigated 30 healthy subjects using six auditory reaction tasks with increasing difficulty and mental effort demands. In the MANOVA analysis we found a significant main effect of task difficulty on both the GBR amplitude (F=7.75; p<0.001) and the auditory evoked N1 potential (F=7.00; p<0.001) with higher amplitudes in the more difficult tasks. In the LORETA region of interest (ROI) analysis, this effect was only due to increased dACC-activity during the GBR-timeframe. For the ROI analysis during the N1 timeframe, in addition to a strong effect of task difficulty in the dACC a similar main effect was found in the auditory association area 22. These findings are in line with a top-down influence of dACC-activity to the auditory association area 22 during the early evoked GBR.

Anxiety disorders are highly prevalent in patients with alcohol use disorder. The purpose of the present study was to examine the neural correlates of behavioral inhibition in alcohol-dependent patients (ICD-10: F 10.2), and in healthy controls and to determine the influence of anxiety on these processes. Therefore, behavioral responses (reaction times; error rates) and event-related potentials of 16 patients with alcohol dependence syndrome and 16 age-and gender-matched healthy controls were recorded while the participants performed an auditory go/no-go task. The patient group was stratified according to their self-rated trait anxiety (STAI) with scores above and below median. We hypothesized that patients suffering from alcohol dependence would show reduced no-go P3 amplitudes involved in response inhibition compared to healthy subjects. In patients with alcoholism and high trait anxiety the decline of no-go P3 amplitudes was expected to be less distinct. The estimation of effect size based on the reaction times of patients with high and low anxiety ratings revealed a cohen's d of 0.61 indicating a small effect. High trait anxiety ratings were also associated with slightly enhanced no-go P3 amplitudes in central brain regions (Mean no-go P3 amplitude at Cz: 10.43 microV) compared to patients with low anxiety scores (Mean 8.98 microV). The effect size (cohen's d) revealed a small effect. Using the Mann-Whitney-U-test for independent samples of the comparison of high- and low-anxious patients, however, did not reveal any significant differences concerning no-go P3 amplitudes. Patients with alcohol use disorder and healthy controls did not differ significantly with regard to reaction time, error rate and no-go P3 amplitudes. This study suggests that no-go P3 amplitudes in patients with alcohol use disorder might be affected to some degree by habitual anxiety. The results emphasize the importance of monitoring trait anxiety in studies regarding cognitive functions in subjects with alcohol use disorder.

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.

Auditory verbal hallucinations (AVH) are one of the most common and most distressing symptoms of schizophrenia. Despite fundamental research, the underlying neurocognitive and neurobiological mechanisms are still a matter of debate. Previous studies suggested that "hearing voices" is associated with a number of factors including local deficits in the left auditory cortex and a disturbed connectivity of frontal and temporoparietal language-related areas. In addition, it is hypothesized that the interhemispheric pathways connecting right and left auditory cortices might be involved in the pathogenesis of AVH. Findings based on Diffusion-Tensor-Imaging (DTI) measurements revealed a remarkable interindividual variability in size and shape of the interhemispheric auditory pathways. Interestingly, schizophrenia patients suffering from AVH exhibited increased fractional anisotropy (FA) in the interhemispheric fibers than non-hallucinating patients. Thus, higher FA-values indicate an increased severity of AVH. Moreover, a dichotic listening (DL) task showed that the interindividual variability in the interhemispheric auditory pathways was reflected in the behavioral outcome: stronger pathways supported a better information transfer and consequently improved speech perception. This detection indicates a specific structure-function relationship, which seems to be interindividually variable. This review focuses on recent findings concerning the structure-function relationship of the interhemispheric pathways in controls, hallucinating and non-hallucinating schizophrenia patients and concludes that changes in the structural and functional connectivity of auditory areas are involved in the pathophysiology of AVH. [ABSTRACT FROM AUTHOR]

Attentiondeficits have been consistently described in schizophrenia. Functional neuroimaging and electrophysiological studies have focused on anterior cingulate cortex (ACC) dysfunction as a possible mediator. However, recent basic research has suggested that the effect of attention is also observed as a relative amplification of activity in modality-associated cortical areas. In the present study, the question was addressed whether an amplification deficit is seen in the auditory cortex of schizophrenic patients during an attention-requiring choice reaction task. Twenty-one drug-free schizophrenic patients and 21 age- and sex-matched healthy controls were studied (32-channel EEG). The underlying generators of the event-related N1 component were separated in neuroanatomic space using a minimum-norm (LORETA) and a multiple dipole (BESA) approach. Both methods revealed activation in the primary auditory cortex (peak latency ≈ 100 ms) and in the area of the ACC (peak latency ≈ 130 ms). In addition, the adapted multiple dipole model also showed a temporal-radial source activation in nonprimary auditory areas (peak latency ≈ 140 ms). In schizophrenic patients, significant activation deficits were found in the ACC as well as in the left nonprimary auditory areas that differentially correlated with negative and positive symptoms. The results suggest that (1) the source in the nonprimary auditory cortex is detected only with a multiple dipole approach and (2) that the N1 generators in the ACC and in the nonprimary auditory cortex are dysfunctional in schizophrenia. This would be in line with the notion that attention deficits in schizophrenia involve an extended cortical network. [Copyright &y& Elsevier]

Auditory verbal hallucinations (AVH) are hallmark symptoms of schizophrenia and have been linked to abnormal activation, connectivity and integration within the auditory, language, and memory brain networks. The interhemispheric miscommunication theory of AVH is based on a steadily growing number of studies using a variety of modalities (EEG, fMRI, DTI) reporting that both altered integrity of the interhemispheric auditory pathways and disturbed functional gamma-band synchrony between right and left auditory cortices significantly contribute to abnormal auditory processing and the emergence of AVH. Moreover, initial studies using pharmacological EEG and 1H MR spectroscopy provided first insights into the underlying neurochemistry of AVH. It has been suggested that the observed interhemispheric gamma-band alterations might be mediated by an excitatory-to-inhibitory (E/I) imbalance due to dysfunction of N -methyl- d -aspartate receptor (NMDAR). In support, a potential NMDAR hypofunction is proposed to be compensated by increased levels of glutamate in prefrontal and auditory brain areas. In this mini-review paper, we used the levels of explanation approach and present how interhemispheric brain connectivity (brain-imaging level) corresponds to auditory perception (cognitive level), and eventually how these parameters are related to changes in neurotransmission (cellular level) and to the occurrence of AVH (clinical level). To the best of our knowledge, this is the first overview that overcomes traditional boundaries and presents converging evidence from different levels of knowledge that validate and support each other, and particularly point toward the role of an interhemispheric miscommunication in AVH. • Levels of explanation approach is used to delineate the interhemispheric miscommunication theory of AVH • Abnormalities of interhemispheric auditory connectivity, language lateralization, NMDAR function and glutamate concentration are related to AVH • Promising NMDAR modulating agents could be a novel personalized symptom-orientated treatment approach [ABSTRACT FROM AUTHOR]

Background: There is growing evidence for abnormalities of certain γ-aminobutyric acid (GABA)-ergic interneurons and their interaction with glutamatergic pyramidal cells in schizophrenia. These interneurons are critically involved in generating neural activity in the γ-band (30–100 Hz) of the electroencephalogram. One example of such γ oscillations is the early auditory evoked γ-band response (GBR). Although auditory processing is obviously disturbed in schizophrenia, there is no direct evidence providing a reduced early auditory evoked GBR so far. We addressed two questions: 1) Is the early auditory evoked GBR decreased regarding power and phase-locking in schizophrenic patients?; and 2) Is this possible decrease a result of reduced activity in the auditory cortex and/or the anterior cingulate cortex (ACC), which were identified as sources of the GBR previously? Methods: We investigated the early auditory evoked GBR and its sources in the ACC and the auditory cortex in 90 medicated patients with schizophrenia and in age-, gender-, and education-matched healthy control subjects with an auditory reaction task. Results: Patients with schizophrenia showed a significant reduction of power and phase-locking of the early auditory evoked GBR. This effect was due to a reduced activity in the auditory cortex and the ACC/medial frontal gyrus region (low-resolution brain electromagnetic tomography analysis). Conclusions: Generally, these findings are in line with earlier reports on the impaired ability of schizophrenic patients in generating γ activity. In addition, this is the first study to demonstrate disturbance of γ activity in auditory processing as assessed by the early auditory GBR power. [Copyright &y& Elsevier]