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Background: Bipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation. Methods: Functional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects. Discussion: The careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications. [ABSTRACT FROM AUTHOR]

Previous studies using imaging techniques such as electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) have identified neurophysiological markers of impaired feedback processing in patients with Borderline Personality Disorder (BPD). These mainly include reduced oscillatory activity in the theta frequency range in the EEG and altered activations in frontal and striatal regions in fMRI studies. The aim of the present study is to integrate these results using a coupling of simultaneously recorded EEG and fMRI. Simultaneous EEG (64-channel) and fMRI (3-Tesla Siemens Prisma) was recorded whilst participants (19 BPD patients and 18 controls) performed a gambling task. Data was analysed for the two imaging techniques separately as well as in a single-trial coupling of both modalities. Evoked theta oscillatory power as a response to loss feedback was reduced in BPD patients. EEG-fMRI coupling revealed an interaction between feedback valence and group in prefrontal regions centering in the dorsolateral prefrontal cortex (dlPFC), with healthy controls showing stronger modulation by theta responses during loss when compared to gain feedback and the opposite effect in BPD patients. Our results show multiple alterations in the processing of feedback in BPD, which were partly linked to impulsivity. The dlPFC was identified as the seed of theta-associated activation differences. [ABSTRACT FROM AUTHOR]

Since our environment typically contains more information than can be processed at any one time due to the limited capacity of our visual system, we are bound to differentiate between relevant and irrelevant information. This process, termed attentional selection, is usually categorized into bottom-up and top-down processes. However, recent research suggests reward might also be an important factor in guiding attention. Monetary reward can bias attentional selection in favor of task-relevant targets and reduce the efficiency of visual search when a reward-associated, but task-irrelevant distractor is present. This study is the first to investigate reward-related target and distractor processing in an additional singleton task using neurophysiological measures and source space analysis. Based on previous studies, we hypothesized that source space analysis would find enhanced neural activity in regions of the value-based attention network, such as the visual cortex and the anterior cingulate. Additionally, we went further and explored the time courses of the underlying attentional mechanisms. Our neurophysiological results showed that rewarding distractors led to a stronger attentional capture. In line with this, we found that reward-associated distractors (compared with reward-associated targets) enhanced activation in frontal regions, indicating the involvement of top-down control processes. As hypothesized, source space analysis demonstrated that reward-related targets and reward-related distractors elicited activation in regions of the value-based attention network. However, these activations showed time-dependent differences, indicating that the neural mechanisms underlying reward biasing might be different for task-relevant and task-irrelevant stimuli. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) is a unique form of non-invasive brain stimulation. Sinusoidal alternating electric currents are delivered to the scalp to affect mostly cortical neurons. tACS is supposed to modulate brain function and, in turn, cognitive processes by entraining brain oscillations and inducing long-term synaptic plasticity. Therefore, tACS has been investigated in cognitive neuroscience, but only recently, it has been also introduced in psychiatric clinical trials. This review describes current concepts and first findings of applying tACS as a potential therapeutic tool in the field of psychiatry. The current understanding of its mechanisms of action is explained, bridging cellular neuronal activity and the brain network mechanism. Revisiting the relevance of altered brain oscillations found in six major psychiatric disorders, putative targets for the management of mental disorders using tACS are discussed. A systematic literature search on PubMed was conducted to report findings of the clinical studies applying tACS in patients with psychiatric conditions. In conclusion, the initial results may support the feasibility of tACS in clinical psychiatric populations without serious adverse events. Moreover, these results showed the ability of tACS to reset disturbed brain oscillations, and thus to improve behavioural outcomes. In addition to its potential therapeutic role, the reactivity of the brain circuits to tACS could serve as a possible tool to determine the diagnosis, classification or prognosis of psychiatric disorders. Future double-blind randomised controlled trials are necessary to answer currently unresolved questions. They may aim to detect response predictors and control for various confounding factors. [ABSTRACT FROM AUTHOR]

Several studies using electroencephalography (EEG) demonstrate that the processing of feedback in patients suffering from borderline personality disorder (BPD) is altered in comparison to healthy controls. Differences occur in the theta (ca. 5 Hz) and high-beta frequency-ranges (ca. 20 Hz) of oscillations in response to negative and positive feedback, respectively. However, alpha (ca. 10 Hz) and low-beta (ca. 15 Hz) oscillations have also been shown to be involved in feedback processing. We hypothesized that additional alterations might occur in these frequency ranges in BPD. Eighteen patients with BPD and twenty-two healthy controls performed a gambling task while 64-channel-EEG was recorded. Induced oscillatory responses to positive (i.e. gain) and negative (i.e. loss) feedback in the alpha and low-beta frequency range were investigated. No significant differences were found in the alpha frequency range. Regarding the low-beta frequency range a significant Group (i.e. BPD vs. healthy controls) × Valence (i.e. gain vs. loss) interaction in the time frame between 600 and 700 milliseconds after feedback was found. This effect showed a significant correlation with symptom severity (assessed with the BSL-23). The results indicate that feedback processing in BPD could be more heavily altered than previously expected, with more severe symptomatology being linked to stronger alterations in oscillatory responses to feedback in the low-beta range. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Growing evidence from neuroimaging studies suggest that emotional and cognitive processes are interrelated. Anatomical key structures in this context are the dorsal and rostral-ventral anterior cingulate cortex (dACC and rvACC). However, up to now, the time course of activations within these regions during emotion-cognition interactions has not been disentangled. In the present study, we used event-related potentials (ERP) and standardized low-resolution electromagnetic tomography (sLORETA) region of interest (ROI) source localization analyses to explore the time course of neural activations within the dACC and rvACC using a modified emotional Stroop paradigm. ERP components related to Stroop conflict (N200, N450 and late negativity) were analyzed. The time course of brain activations in the dACC and rvACC was strikingly different with more pronounced initial responses in the rvACC followed by increased dACC activity mainly at the late negativity window. Moreover, emotional valence modulated the earlier N450 stage within the rvACC region with higher neural activations in the positive compared to the negative and neutral conditions. Emotional arousal modulated the late negativity stage; firstly in the significant arousal × congruence ERP effect and then the significant higher current density in the low arousal condition within the dACC. Using sLORETA source localization, substantial differences in the activation time courses in the dACC and rvACC could be found during the emotional Stroop task. We suggest that during late negativity, within the dACC, emotional arousal modulated the processing of response conflict, reflected in the correlation between the ex-Gaussian µ and the current density in the dACC. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. Structure: A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). Conclusions: This article aims to outline the rationale, design, and methods of these individual studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Over the last decade, there has been growing interest in aberrant salience as a precursor of positive symptoms in schizophrenia. The present study investigates the neurophysiology of attentional capture by salient stimuli in the visual modality. Evoked oscillatory activity in the gamma frequency range (40 Hz) was assessed during visual processing of physically salient distracters and evaluated in relation to schizotypy and its positive, negative and disorganized dimension. The early evoked visual gamma-band response (GBR) was assessed for 24 healthy participants using EEG time-frequency analysis. Physical salience was constituted by colored stimuli diverting from an ongoing baseline condition. schizotypal personality traits were measured by the schizotypal personality questionnaire (SPQ; Raine in Schizophr Bull 17:555-564, ). The early evoked visual GBR was significantly pronounced in the physically salient distracter condition. GBR signal power was significantly correlated with positive schizotypal personality traits (r = 0.588; p = 0.024*). Our results indicate that the early evoked GBR in visual processing of physically salient distracters is associated with schizotypy. These findings refer to the phenomenology of aberrant salience by bridging the gap to neurophysiological research on early sensory selection and attentional capture in the schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

Several studies suggest that attention to emotional content is related to specific changes in central information processing. In particular, event-related potential (ERP) studies focusing on emotion recognition in pictures and faces or word processing have pointed toward a distinct component of the visual-evoked potential, the EPN ('early posterior negativity'), which has been shown to be related to attention to emotional content. In the present study, we were interested in the existence of a corresponding ERP component in the auditory modality and a possible relationship with the personality dimension extraversion-introversion, as assessed by the NEO Five-Factors Inventory. We investigated 29 healthy subjects using three types of auditory choice tasks: (1) the distinction of syllables with emotional intonation, (2) the identification of the emotional content of adjectives and (3) a purely cognitive control task. Compared with the cognitive control task, emotional paradigms using auditory stimuli evoked an EPN component with a distinct peak after 170 ms (EPN 170). Interestingly, subjects with high scores in the personality trait extraversion showed significantly higher EPN amplitudes for emotional paradigms (syllables and words) than introverted subjects. [ABSTRACT FROM AUTHOR]

Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients. [ABSTRACT FROM AUTHOR]

The regulation of brain activation, as assessed with the EEG, is a state modulated trait. A decline to lowered EEG-vigilance states has been found to be associated with emotional instability in older studies, but has not been systematically studied in patients with borderline personality disorder (BPD). Twenty unmedicated BPD patients were compared to 20 unmedicated patients with obsessive-compulsive disorder (OCD) as well as 20 healthy controls concerning their EEG-vigilance regulation over a 5-min period assessed with an algorithm classifying every artefact-free 2-s EEG segment into the EEG-vigilance state (A1–A3, B (=non-A)). If the alpha power was posterior more than 55% of the whole alpha power (anterior + posterior) in the artefact-free EEG-segments, that segment was marked as A1, if it was anterior more than 55% of the whole alpha power, as A3. For A2 the following rule was defined: Posterior or anterior alpha between 50 and 55% of the whole alpha power. BPD patients showed significantly lower rates of EEG-vigilance state A compared to OCD patients, indicating a lowered EEG-vigilance. All three groups showed a decrease in the rate of EEG-vigilance state A over the 5 min recording period in line with a lowering of vigilance. The study provides evidence for a less stable regulation of EEG-vigilance in BPD compared to OCD patients and is in line with concepts postulating that the behavioural pattern with sensation seeking and impulsivity in BPD has a compensatory and autoregulatory function to stabilize activation of the CNS. [ABSTRACT FROM AUTHOR]

The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 ± 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson’s correlations: rho = −0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = −0.60, p < 0.05) but were pronounced in the female group (rho = −0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity. [ABSTRACT FROM AUTHOR]

An important reason for the interest in P300 event-related potentials are findings in patients with psychiatric disorders like schizophrenia or alcoholism in which attenuations of the P300 amplitude are common findings. The P300 wave has been suggested to be a promising endophenotype for genetic research since attenuations of the amplitude and latency can be observed not only in patients but also in relatives. In parallel, the search for genes involved in the pathogenesis of psychiatric disorders has revealed for both, schizophrenia and alcoholism an association with a DRD3 Ser9Gly polymorphism in a number of studies. In the present study, we have investigated 124 unrelated healthy subjects of German descent and have found diminished parietal and increased frontal P300 amplitudes in Gly9 homozygotes in comparison to Ser9 carriers. This finding suggests a possible role of the DRD3 receptor gene in the interindividual variation of P300 amplitudes. Further studies should address the direct role of the DRD3 Ser9Gly polymorphism in attenuated P300 amplitudes in psychiatric disorders like schizophrenia or alcoholism.Neuropsychopharmacology (2006) 31, 1335–1344. doi:10.1038/sj.npp.1300984; published online 4 January 2006 [ABSTRACT FROM AUTHOR]

Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [123I]β-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of I 0 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [123I]β-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [123I]β-CIT binding for the midbrain · pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: ρ = 0.69, p<0.05, and ρ = 0.80, p <0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA)A-receptors play a crucial role in the generation of electroencephalogram (EEG) oscillations and evoked potentials (ERPs). The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA β2 (GABRB2) and γ2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotide substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed in 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/P200-complex). No genotypic association was found for the GABRB2 nucleotide exchange polymorphism with any electrophysiological parameter. A significant association was found between the genotype of the intronic GABRG2 G→A nucleotide exchange and the event-related N100/P200 (ANOVA: F=3.81; df=2; P=0.026). A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002). Post hoc analysis of this association with current density analysis in three-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefrontal cortex. Taking into account the risk of false-positive association findings attributable to multiple testing, our results encourage further replication studies to examine the phenotype-genotype relationship of GABRG2 gene variants and event-related prefrontal activity. [ABSTRACT FROM AUTHOR]

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]