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Disrupted auditory networks play an important role in the pathophysiology of psychosis, with abnormalities already observed in individuals at clinical high-risk for psychosis (CHR). Here, we examine structural and functional connectivity of an auditory network in CHR utilising state-of-the-art electroencephalography and diffusion imaging techniques. Twenty-six CHR subjects and 13 healthy controls (HC) underwent diffusion MRI and electroencephalography while performing an auditory task. We investigated structural connectivity, measured as fractional anisotropy in the Arcuate Fasciculus (AF), Cingulum Bundle, and Superior Longitudinal Fasciculus-II. Gamma-band lagged-phase synchronisation, a functional connectivity measure, was calculated between cortical regions connected by these tracts. CHR subjects showed significantly higher structural connectivity in the right AF than HC (p <.001). Although non-significant, functional connectivity between cortical areas connected by the AF was lower in CHR than HC (p =.078). Structural and functional connectivity were correlated in HC (p =.056) but not in CHR (p =.29). We observe significant differences in structural connectivity of the AF, without a concomitant significant change in functional connectivity in CHR subjects. This may suggest that the CHR state is characterised by a decoupling of structural and functional connectivity, possibly due to abnormal white matter maturation. [ABSTRACT FROM AUTHOR]

It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP). Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed. There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP. Our study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals. [ABSTRACT FROM AUTHOR]

Objectives: Disturbances in the gamma-frequency band of electroencephalography (EEG) measures are among the most consistently observed intermediate phenotypes in schizophrenia. We assessed whether genetic variations are associated with gamma-band activity. Methods: We performed a genome-wide association analysis of the early auditory evoked gamma-band response in schizophrenia affected subjects and healthy control individuals (in total N = 315). Results: No marker surpassed the threshold for genome-wide significant association. Several of the markers that were closest to significance mapped to genes involved in neuronal development and the Neuregulin-ErbB signalling network, such as NRG2 and KALRN. Using a gene-set enrichment analysis, we found suggestive evidence for association with genes involved in EEG abnormality (P = .048). Conclusions: We identified no marker genome-wide significantly associating with gamma response; independent replication of the gene-set analysis result and larger sample sizes will be required to provide leads to cellular pathways involved in gamma-band activity. [ABSTRACT FROM AUTHOR]

Objectives: Aberrant salience mainly is attributed to excessive dopaminergic processing in the ventral striatum. Increased gamma power during sensory processing of physical salience has been shown to be associated with positive trait schizotypy. In the present study, this is assessed in patients with schizophrenia. Methods: The early evoked visual gamma-band response (GBR) at 40 Hz was assessed for a schizophrenia patient group (N = 22) and a matched healthy control group (N = 22) applying EEG time-frequency analysis. The GBR was assessed for two conditions within a visual detection paradigm: a target with or without a physically salient distracter and evaluated in relation to the PANSS. Results: A 2 × 2 ANOVA revealed a significant main effect of condition and a trend interaction of group and condition for the GBR, with highest power for schizophrenia patients in the physically salient distracter condition. Moreover, evoked GBR power in this condition was correlated with positive (r = 0.664; P = 0.001**) and disorganised (r = 0.618; P = 0.002**) schizophrenia symptoms. Conclusions: Evoked GBR power during processing of physical salience in schizophrenia was associated with positive symptoms. We suggest that abnormal processing of physically salient stimuli might be involved in the pathophysiological genesis of positive symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives. Gamma-band oscillations (e.g., the early auditory evoked gamma-band response, aeGBR) have been suggested to mediate cognitive and perceptual processes by driving the synchronization of local neuronal populations. Reduced aeGBR is a consistent finding in patients with schizophrenia and high-risk subjects, and has been proposed to represent an endophenotype for the illness. However, it is still unclear whether this reduction represents a deficit in sensory or cognitive processes, or a combination of the two. The present study investigated this question by manipulating the difficulty of an auditory reaction task in patients with first-episode schizophrenia and healthy controls. Methods. A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and 22 healthy controls during two conditions of an auditory reaction task: an easy condition that merely required low-level vigilance, and a difficult condition that placed significant demands on attention and working memory. Results. In contrast to healthy controls, patients failed to increase aeGBR power and phase-locking in the difficult condition. In patients, aeGBR power and phase-locking indices were associated with working memory deficits. Conclusions. The observed results confirm the applicability of aeGBR disturbances as a stable endophenotype of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their origin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives. Auditory verbal hallucinations (AVH) are among the most common symptoms in schizophrenia. Earlier studies suggest changes in the structural connectivity of auditory areas involved in the pathophysiology of auditory hallucinations. Combining diffusion tensor imaging (DTI) and fibre tractography provides a unique opportunity to visualize and quantify entire fibre bundles. Methods. Fibre tracts connecting homotopic auditory areas via the corpus callosum were identified with DTI in ten first episode paranoid schizophrenia patients and ten healthy controls. Regions of interest were drawn manually, to guide tractography, and fractional anisotropy (FA) - a measure of fibre integrity - was calculated and averaged over the entire tract for each subject. Results. There was no difference in the FA of the interhemispheric auditory fibres between schizophrenic patients and healthy controls. However, the subgroup of patients hearing conversing voices showed increased FA relative to patients without these symptoms ( P == 0.047) and trendwise increased FA relative to healthy controls ( P == 0.066). In addition, a trendwise correlation between FA values and AVH symptoms ( P == 0.089) was found. Conclusions. Our findings suggest that in addition to local deficits in the left auditory cortex and disturbed fronto-temporal connectivity, the interhemispheric auditory pathway might be involved in the pathogenesis of AVH. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been reported to exert significant antidepressant effects in patients with major depression. Several recent studies found an improvement of depressive symptoms in drug-free patients. Here we report the case of a 66-year-old female patient suffering from recurrent major depressive episodes who underwent anodal tDCS of the left dorsolateral PFC over 4 weeks as an add-on treatment to a stable antidepressant medication. Only a modest improvement of depressive symptoms was observed after tDCS, i.e. reduction of the baseline scores in the Hamilton Depression Rating Scale from 23 to 19 and in the Beck Depression Inventory from 27 to 20. However, there was an increase from 52 to 90% in the Regensburg Verbal Fluency Test. In addition, EEG was used to assess the acute effects of tDCS. Low resolution brain electromagnetic tomography (LORETA) showed a left unilateral focal effect (25-40% reduced power) in the delta, theta and alpha frequency bands. The same effect appeared in the surface analysis of the EEG. The absolute, as well as the relative power decreased significantly in the delta, theta and alpha bands after a comparison of the spectral analysis. Though tDCS over 4 weeks did not exert clinically meaningful antidepressant effects in this case of therapy-resistant depression, the findings for cognitive measures and EEG suggest that beneficial effects may occur in depressed subjects and future studies need to further explore this approach also in therapy-resistant major depression. [ABSTRACT FROM AUTHOR]

There is increasing evidence that obsessive-compulsive disorder (OCD) is associated with a dysfunction of cortico-striato-thalamo-cortical neuronal circuits. In order to examine treatment-related changes in neuronal processes, a drug-naive female patient with OCD (subtype: washing/contamination fear) and an age- and gender-matched healthy control were repeatedly tested using functional magnetic resonance imaging (MRI) during the presentation of a symptom provocation task. Patient-specific visual stimuli of symptom provoking situations were compared with disgust provoking and neutral pictures. FMRI scanning was conducted at the beginning, during and upon completion of an inpatient treatment. During the treatment period of more than eight weeks (combined behavioural and systemic couple therapy) the patient filled out a therapy process questionnaire (TPQ) which was administered daily. Results show a phase transition-like change characterized by a sudden reduction of clinical symptoms as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in the middle of the treatment period. Before the discontinuous symptom reduction occurred, the dynamic complexity of the TPQ-time series increased which might be indicative for a critical instability of the system. The fMRI results at the beginning of the treatment suggest strong activities in various brain regions, especially in the anterior cingulate cortex. The results of the second and third acquisition revealed comparably smaller OCD-related neuronal responses. The results may indicate that important clinical changes are taking place during the psychotherapy process which correspond to changing patterns of brain activation as well as to critical instabilities and phase-transition like phenomena in the time-series of the patient's daily self-report data. [ABSTRACT FROM AUTHOR]