Saskia Steinmann

Interhemispheric auditory connectivity: structure and function related to auditory verbal hallucinations

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.

Conscious auditory perception related to long-range synchrony of gamma oscillations

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.

Oscillatory responses to reward processing in borderline personality disorder

Objectives. Previous electrophysiological studies have confirmed impaired reward processing in patients with BPD. However, it is not clear which aspects of reward processing are affected and which brain regions are involved. The present study investigated both evoked and induced event-related oscillations (EROs) to feedback events (thought to represent different aspects of feedback processing), and used source localization (sLORETA) to assess activity in two areas known to contribute to reward processing, the dorsomedial prefrontal/anterior cingulate cortex (dmPFC/ACC) and the orbitofrontal cortex (OFC). Methods. Eighteen patients with BPD and 22 healthy controls performed a gambling task, while 64-channel electroencephalographic activity was recorded. Evoked and induced theta and high-beta band EROs as well as activity in the two regions of interest were investigated depending on the valence and magnitude of feedback events. Results. Theta-band responses to negative feedback were reduced in BPD, an effect that involved only evoked responses and the dmPFC/ ACC region, and was associated with trait impulsivity in patients. sLORETA analyses revealed disturbed evoked responses depending on feedback magnitude in the theta (OFC) and high-beta (dmPFC/ACC and OFC) frequency range. Conclusions. The results indicate multiple dysfunctions of feedback processing in patients with BPD, implicating several distinct subsets of reward-processing mechanisms.

Generators and Connectivity of the Early Auditory Evoked Gamma Band Response

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.

Functional relevance of interhemispheric fiber tracts in speech processing

Abstract Speech processing requires a timely coordination of different relative broad distributed cortical and subcortical interhemispheric gray matter (GM) areas, which interact through white matter (WM) fiber tracts. These interacting large-scale brain networks have to identify different linguistical types, such as phonemes, morphemes, syllables, phrases, words, plus the syntactic relation between them as well as the prosodic information: The linguistic processing is mainly arranged by the perisylvian region in the left hemisphere (LH), whereas same regions in the right hemisphere (RH) seems to be specialized in the implementation of prosodic information. Prosody comprises individual intonation, accent pattern and rhythm and, among others, contributes to the linguistic structure of an utterance (e.g. indicating word- and sentence structure) as well as conveys affective and emotional information. Thus, both hemispheres seem to contribute to speech processes differentially and have to coordinate their information via the Corpus Callosum (CC). Recent MRI study revealed a remarkable interindividual variability in size and shape of the CC. Findings based on DTI measurements evinced, that stronger anatomical fibers supported a better information transfer and consequently improved speech perception. This detection indicates a specific structure–function relationship, which seems to be interindividual different. The following review article will discuss recent findings concerning the structure–function relationship of the interhemispheric pathways in speech processing as well as their contribution in speech-related symptoms like dyslexia, stutter and auditory verbal hallucinations (AVH).

Auditory verbal hallucinations related to altered long-range synchrony of 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.

Glutamatergic deficit and schizophrenia-like negative symptoms: new evidence from ketamine-induced mismatch negativity alterations in healthy male humans

Background Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers. Methods We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization. Results Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus. Limitations The sample included only men within a tight age range of 20–32 years. Conclusion The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.

The role of effective connectivity between the task-positive and task-negative network for evidence gathering [Evidence gathering and connectivity]

&NA; Reports linking a ‘jumping‐to‐conclusions’ bias to delusions have led to growing interest in the neurobiological correlates of probabilistic reasoning. Several brain areas have been implicated in probabilistic reasoning; however, findings are difficult to integrate into a coherent account. The present study aimed to provide additional evidence by investigating, for the first time, effective connectivity among brain areas involved in different stages of evidence gathering. We investigated evidence gathering in 25 healthy individuals using fMRI and a new paradigm (Box Task) designed such as to minimize the effects of cognitive effort and reward processing. Decisions to collect more evidence (‘draws’) were contrasted to decisions to reach a final choice (‘conclusions’) with respect to BOLD activity. Psychophysiological interaction analysis was used to investigate effective connectivity. Conclusion events were associated with extensive brain activations in widely distributed brain areas associated with the task‐positive network. In contrast, draw events were characterized by higher activation in areas assumed to be part of the task‐negative network. Effective connectivity between the two networks decreased during draws and increased during conclusion events. Our findings indicate that probabilistic reasoning may depend on the balance between the task‐positive and task‐negative network, and that shifts in connectivity between the two may be crucial for evidence gathering. Thus, abnormal connectivity between the two systems may significantly contribute to the jumping‐to‐conclusions bias. HighlightsWe examined fMRI activity and connectivity patterns during evidence gathering.Activations in the task‐negative network (TNN) characterized evidence collection.Activations in the task‐positive network (TPN) marked the time‐point of conclusion.Effective connectivity between TNN and TPN increased during conclusion events.Probabilistic reasoning may depend on the balance between TPN and TNN.

Relationship Between Neuroanatomical and Serotonergic Hypotheses of Obsessive-Compulsive Disorder: A Combined Functional Magnetic Resonance Imaging–Evoked Potential Study

OBJECTIVE The so-called neuroanatomical hypothesis (with an increased activity of orbitofrontal cortex [OFC]) and the serotonergic hypothesis (with low activity in this system) have been discussed regarding the pathogenesis of obsessive-compulsive disorder (OCD) for decades. This study aimed to look for a relationship between the 2 pathogenetic concepts. METHODS Nineteen OCD patients (8 female, 11 male, mean ± SD age = 33.37 ± 11.73 years, Yale-Brown Obsessive Compulsive Scale: 21.79 ± 6.59; diagnosed by ICD-10/DSM-IV-TR) were compared to 19 matched healthy controls (8 female, 11 male, mean ± SD age = 31.63 ± 10.79 years) and investigated (2012-2014) with the loudness dependence of auditory-evoked potentials (LDAEP) as a marker of the synaptic serotonergic activity and functional magnetic resonance imaging (fMRI) during the delay discounting paradigm, inducing OFC blood-oxygen level-dependent activity in the 2 groups. RESULTS There were significant correlation coefficients between LDAEP (eLORETA right side) and fMRI OFC activities (anatomic region of interest) within the delay discounting paradigm (immediate vs control) in patients with OCD (r = -0.554; P = .014). LDAEP differed between the 2 groups with larger LDAEP at Cz in OCD patients indicating low serotonergic activity (0.28 ± 0.14 vs 0.20 ± 0.10 µV/10 dB, F₂,₃₅ = 4.66, P = .016). fMRI activations of dorsolateral and medial prefrontal cortex as well as ventral striatum (functional region of interest) were different between OCD and healthy volunteers. CONCLUSIONS The 2 main pathophysiologic hypotheses of OCD seem to be related to each other as measured by LDAEP and fMRI OFC activity during the delay discounting task. This could be interpreted as a further hint that low serotonergic activity induces altered OFC responsivity, which has to be treated in each patient with OCD by a serotonin agonist.

fMRI correlates of jumping-to-conclusions in patients with delusions: Connectivity patterns and effects of metacognitive training

Background Reasoning biases such as the jumping-to-conclusions bias (JTC) are thought to contribute to delusions. Interventions targeting these biases such as metacognitive training (MCT) may improve delusions. So far, it is not clear whether JTC depends on dopaminergic reward areas that constitute the main action locus of antipsychotic drugs, or on additional cortical areas. The present study aimed to investigate fMRI activation and functional connectivity patterns underlying JTC, and their changes following MCT, in patients with delusions. Methods Participants were 25 healthy individuals and 26 patients with current delusions who were either medication-free or on stable medication without sufficient response. We assessed (1) BOLD activity in the task-positive (TPN), task-negative (TNN), and subcortical reward network (RN); (2) Psychophysiological interactions (PPI) of peak activation areas. Results Presence of JTC (irrespective of group) was associated with lower RN activity during conclusion events, and with increased effective connectivity between TPN and TNN during draw events. Following MCT, changes were observed in TPN activity and in effective connectivity of inferior parietal cortex (part of the TPN) with all three target networks. Conclusion JTC is associated not only with reward system areas that constitute the main target of antipsychotic drugs, but also with cortical areas, particularly of the TPN.