Search

Current classification systems (ICD-10 and DSM-IV) require a quantitative criterion for differentiating depressive states, suggesting a correlation between the number of symptoms, i.e., the pervasiveness of the syndrome, and the subtype of the illness. All the symptoms (within those contained in the diagnostic lists) are assumed to have comparable value. To investigate the relevance of the number and the type of symptoms reported by 196 patients suffering from depression, we compared the symptoms using independent indicators of severity such as the Clinical Global Index (CGI) and the social functioning subscale of the Global Assessment of Functioning (GAF). A second comparison using the same indicators was made between qualitatively distinct categories of DSM-IV and ICD-10 (i.e., melancholic v nonmelancholic, somatic v nonsomatic, and psychotic v nonpsychotic). There was evidence that increasing numbers of symptoms actually reflect higher levels of severity, but the categorizations that were mainly based on qualitative criteria (e.g., melancholia, somatic syndrome, etc.) usually attained better discrimination compared with those based on the number of symptoms. Moreover, certain symptoms (usually those indicated as endogenous) were more likely to be associated with greater severity and pervasiveness. Finally, the results clearly showed that different symptoms had different weight in establishing the gradient of severity.

The present study investigates the relation of perceived arousal (continuous self-rating), autonomic nervous system activity (heart rate, heart rate variability) and musical characteristics (sound intensity, musical rhythm) upon listening to a complex musical piece. Twenty amateur musicians listened to two performances of Chopin's "Tristesse" with different rhythmic shapes. Besides conventional statistical methods for analyzing psychophysiological reactions (heart rate, respiration rate) and musical variables, semblance analysis was used. Perceived arousal correlated strongly with sound intensity; heart rate showed only a partial response to changes in sound intensity. Larger changes in heart rate were caused by the version with more rhythmic tension. The low-/high-frequency ratio of heart rate variability increased--whereas the high frequency component decreased--during music listening. We conclude that autonomic nervous system activity can be modulated not only by sound intensity but also by the interpreter's use of rhythmic tension. Semblance analysis enables us to track the subtle correlations between musical and physiological variables.

The topographical configuration of the spontaneous brain electric fields is considered to contain relevant information about the pattern of the generating cortical electrochemical activation and the associated cognitive processes. Space oriented segmentation allows to break down the stream of the spontaneous EEG into brain electric microstates with stable configuration of the fields. It has been shown that the mean duration of the microstates was consistent with the duration of elementary steps of cognitive processes, and that different topographies of the microstates are associated with different cognitive modalities. Space-oriented segmentation was applied to the resting EEG of 22 depressive patients and of 22 controls. The topographical variance was larger, and the most prominent brain electrical microstates of the EEG epochs were significantly shorter in the depressive group than in controls. No differences were found for the shortest microstates. This result cannot be explained by group differences in the frequency domain of the EEG. No topographical differences were found between the microstates of depressives and those of controls. Based on previous results in healthy volunteers during spontaneous cognition and in schizophrenic patients, the findings indicate that formal aspects rather than the modalities of the stream of cognition are altered in depression. Automatic and schematic processing, and attentional deficits as described in depressive patients might account for the finding of less sustained brain electrical microstates.

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA–pallidum and the left M1–thalamus connection in healthy controls, and in the left pre-SMA–SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction.

One Hertz (1 Hz) repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for auditory verbal hallucinations (AVH). Theta burst protocols (TBS) show longer after-effects. This single-blind, randomized controlled study compared continuous TBS with 1Hz rTMS in a 10-day treatment. Patients were diagnosed with schizophrenia or schizoaffective disorder. TBS demonstrated equal clinical effects compared to 1Hz TMS.

Self-efficacy has been identified as one of the most consistent variables that predict the outcome of alcohol treatment. However, many previous studies in this field failed to control for other important predictors (e.g., dependences severity, psychiatric symptoms, and treatment goal). Our study's first goal was to evaluate the predictive value of self-efficacy when most other relevant variables were statistically controlled. The second goal was to compare the predictive values of self-efficacy assessed with the Situational Confidence Questionnaire (SCQ), and general self-efficacy assessed with a single question.Four hundred and fifteen patients with alcohol dependence from 12 residential alcohol use disorder (AUD) treatment programs were assessed at treatment admission, discharge, and the 1-year follow-up. A stepwise logistic regression for abstinence was calculated using all predictors. For those predictors that were significant, a Cox survival regression analysis was performed to predict the time to the first drink after discharge.Only abstinence as treatment goal, alcohol use during treatment, and general self-efficacy as measured by 1 question were revealed to be significant predictors in the stepwise regression, whereas all other variables, including self-efficacy as measured by the SCQ, were not significantly associated with abstinence at the 1-year follow-up. Cox survival regression analysis showed a significant difference in the time to first alcohol use between patients with maximum general self-efficacy and those with lower general self-efficacy, when the other 2 significant variables were controlled for.General self-efficacy, that is, the patients' own prognosis of his success in remaining abstinent, was a central variable in predicting residential alcohol dependence treatment outcome. Self-efficacy showed a more accurate prognosis of outcome when it was assessed with just 1 question, than when assessed with the SCQ. With this simplified assessment, knowledge of the prognostic value of self-efficacy could be made applicable for everyday practice.

While functional changes linked to second language learning have been subject to extensive investigation, the issue of learning-dependent structural plasticity in the fields of bilingualism and language comprehension has so far received less notice. In the present study we used voxel-based morphometry to monitor structural changes occurring within five months of second language learning. Native English-speaking exchange students learning German in Switzerland were examined once at the beginning of their stay and once about five months later, when their German language skills had significantly increased. We show that structural changes in the left inferior frontal gyrus are correlated with the increase in second language proficiency as measured by a paper-and-pencil language test. Contrary to the increase in proficiency and grey matter, the absolute values of grey matter density and second language proficiency did not correlate (neither on first nor on second measurement). This indicates that the individual amount of learning is reflected in brain structure changes, regardless of absolute proficiency.

Evidence of hemispheric asymmetries in schizophrenia has been reported from different research areas. Asymmetries in evoked potential P300 topography are still controversial because of inconsistent findings. In the present study, previous results of abnormal lateralization of P300 were replicated in stabilized residual schizophrenic patients. Auditory P300 was recorded during an oddball task in which subjects detected rare target stimuli. Schizophrenic patients had the P300 peak shifted to the right hemisphere and differed significantly from age- and sex-matched normal control subjects who had left-lateralized P300 peaks. A comparison of different methods of assessment and analysis of the topographical features of the P300 electric fields showed that the extraction of reference-independent descriptors of P300 topography is a reliable and sensitive method for statistical handling of the maps. The results suggest left hemispheric dysfunction during cognitive tasks in a subgroup of schizophrenic patients. Inconsistencies between previous studies are likely to be due to heterogeneous patient groups, which may have included patients in an acute schizophrenic episode or patients in clinical remission. Investigation of the clinical meaning of P300 alterations requires careful psychopathological definition of the patient groups.

BACKGROUND: Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF). METHODS: Nineteen control subjects and 20 MDD patients were investigated using arterial spin labeling (ASL) at 3T in the morning to quantify resting state CBF. Afterwards wrist actigraphy was recorded for 24h. CBF, group and activity level (AL) were entered into a whole brain general linear model. RESULTS: MDD patients had reduced AL. Both groups had linear associations of AL and CBF in bilateral rostral prefrontal cortex. Groups differed in four clusters associated with motor control. In controls a positive association was found in the left caudal cingulate zone (CCZ) and an inverse association in the right external globus pallidus (GPe). MDD patients had positive associations in the right orbitofrontal cortex and inverse associations in the left supplemental motor area. LIMITATIONS: Patients were on antidepressant medication. CONCLUSIONS: The pattern of associations between CBF and AL suggest disbalanced motor control in MDD. Findings are in line with the hypothesis of dopamine deficits contributing to motor retardation in MDD. Language: en

Motor symptoms in schizophrenia occur frequently and are relevant to diagnosis and antipsychotic therapy. To date motor symptoms are difficult to assess and their pathobiology is a widely unresolved issue. The Bern Psychopathology Scale for the assessment of system-specific psychotic symptoms (BPS) was designed to identify homogenous patient groups by focusing on three domains: language, affectivity and motor behavior. The present study aimed to validate the motor behavior domain of the BPS using wrist actigraphy. In total, 106 patients were rated with the BPS and underwent 24 h continuous actigraphy recording. The ratings of the global severity of the motor behavior domain (GSM) as well as the quantitative and the subjective items of the motor behavior domain of the BPS were significantly associated with actigraphic variables. In contrast, the qualitative items of the motor domain failed to show an association with actigraphy. Likewise, scores of the language and the affectivity domains were not related to actigraphic measures. In conclusion, we provided substantial external validity for global, quantitative and subjective ratings of the BPS motor behavior domain. Thus, the BPS is suitable to assess the dimension of quantitative motor behavior in the schizophrenia spectrum.

Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30–50 Hz) and below-gamma (1.5–30 Hz) bands in drug-naive patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-naive patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.

Patients with panic disorder (PD) have a bias to respond to normal stimuli in a fearful way. This may be due to the preactivation of fear-associated networks prior to stimulus perception. Based on EEG, we investigated the difference between patients with PD and normal controls in resting state activity using features of transiently stable brain states (microstates). EEGs from 18 drug-naive patients and 18 healthy controls were analyzed. Microstate analysis showed that one class of microstates (with a right-anterior to left-posterior orientation of the mapped field) displayed longer durations and covered more of the total time in the patients than controls. Another microstate class (with a symmetric, anterior-posterior orientation) was observed less frequently in the patients compared to controls. The observation that selected microstate classes differ between patients with PD and controls suggests that specific brain functions are altered already during resting condition. The altered resting state may be the starting point of the observed dysfunctional processing of phobic stimuli.

Alcohol use disorder (AUD) and depressive disorders often co-occur. Findings on the effects of major depressive disorder (MDD) or depressive symptoms on posttreatment alcohol relapse are controversial. The study's aim is to examine the association of MDD and depressive symptoms with treatment outcomes after residential AUD programs. In a naturalistic-prospective, multisite study with 12 residential AUD treatment programs in the German-speaking part of Switzerland, 64 patients with AUD with MDD, 283 patients with AUD with clinically significant depressive symptoms at admission, and 81 patients with AUD with such problems at discharge were compared with patients with AUD only on alcohol use, depressive symptoms, and treatment service utilization. MDD was provisionally identified at admission and definitively defined at discharge. Whereas patients with MDD did not differ from patients with AUD only at 1-year follow-up, patients with AUD with clinically significant depressive symptoms had significantly shorter time-to-first-drink and a lower abstinence rate. These patients also had elevated AUD indices and treatment service utilization for psychiatric disorders. Our results suggest that clinically significant depressive symptoms are a substantial risk factor for relapse so that it may be important to treat them during and after residential AUD treatment programs.

Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyrus, right thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia. In addition, CBF of cortical areas critical for motor control was associated with volitional motor behavior, which may be a compensatory mechanism for basal ganglia dysfunction.

INTRODUCTION: Mild unconjugated hyperbilirubinemia seems to be more common in patients with disorders from the schizophrenic spectrum than in other psychiatric patients or in the general population and has been linked to brain alterations. This spectrum however contains a number of diagnostic entities that might not share the same etiological and environmental factors. METHODS: 325 hospital admissions were analysed over a one-year period. RESULTS: We found an association of acute and transient psychotic disorders (ATPD) with total bilirubin level and rate of elevated total bilirubin that was increased compared to paranoid schizophrenia and schizoaffective disorder, all patients, and was higher than in the general population. Concomitant increased direct bilirubin might suggest that reduced UGT activity, causing Gilbert's syndrome in the general population, is not the reason for elevated bilirubin in ATPD. CONCLUSIONS: The difference between ATPD and schizophrenia/schizoaffective disorder might be due to disorder severity, aetiology, or environmental factors that influence enzyme activity.

Attentional factors are thought to affect eye-tracking patterns. The present study examined the hypothesis that specific quantitative features of eye tracking would be correlated with the amplitude of a component of the auditory evoked potential, the N100, which is known to be enhanced by arousal and selective attention. We studied 12 clinically stable schizophrenic patients by means of DC-electro-oculography. The frequency and amplitude of different types of saccades (catchup, backup, anticipatory saccades, and square wave jerks) were assessed. The results suggest that small and large saccades, as classified by a simple amplitude criterion (4°), have differential meanings and indicate that enhanced amplitudes of small saccades are an effect of arousal.

Patients with schizophrenia are impaired in many aspects of auditory processing, but indirect evidence suggests that intensity perception is intact. However, because the extraction of meaning from dynamic intensity relies on structures that appear to be altered in schizophrenia, we hypothesized that the perception of auditory looming is impaired as well. Twenty inpatients with schizophrenia and 20 control participants, matched for age, gender, and education, gave intensity ratings of rising (looming) and falling intensity sounds with different mean intensities. Intensity change was overestimated in looming as compared with receding sounds in both groups. However, healthy individuals showed a stronger effect at higher mean intensity, in keeping with previous findings, while patients with schizophrenia lacked this modulation. We discuss how this might support the notion of a more general deficit in extracting emotional meaning from different sensory cues, including intensity and pitch.

Background: Delusional misidentification syndrome (DMS) is of considerable interest, but rarely diagnosed clinically. It is supposed to occur relatively frequently in schizophrenia, and to be related to the pathophysiology of face processing. Two antagonistic forms of DMS are the hypoidentification (Capgras) and hyperidentification (Fregoli) syndromes. We aimed to highlight differences between these subtypes using a face recognition memory task. Methods: Twenty schizophrenia patients (10 with DMS) and 21 healthy controls memorized the images of unknown neutral faces (targets). After a 10-min interval, accuracy and reaction times were recorded during a recognition task consisting of targets (newly learned faces), as well as familiar and unfamiliar face images. The 10 DMS patients could be further subdivided into 6 patients with Fregoli syndrome and 4 with Capgras syndrome. Results: Patients with DMS had longer reaction times than controls or patients without DMS (p < 0.001). Fregoli patients had longer reaction times (p < 0.001) and lower discrimination accuracy than Capgras patients (p = 0.019). These results were independent of other clinical variables. Conclusions: Face recognition differs between clinically identified subgroups of schizophrenia and between types of DMS. The results indicate independent pathophysiological mechanisms for Capgras (hypoidentification) and Fregoli (hyperidentification) syndromes in schizophrenia.

Phase locking or synchronization of brain areas is a key concept of information processing in the brain. Synchronous oscillations have been observed and investigated extensively in EEG during the past decades. EEG oscillations occur over a wide frequency range. In EEG, a prominent type of oscillations is alpha-band activity, present typically when a subject is awake, but at rest with closed eyes. The spectral power of alpha rhythms has recently been investigated in simultaneous EEG/fMRI recordings, establishing a wide-range cortico-thalamic network. However, spectral power and synchronization are different measures and little is known about the correlations between BOLD effects and EEG synchronization. Interestingly, the fMRI BOLD signal also displays synchronous oscillations across different brain regions. These oscillations delineate so-called resting state networks (RSNs) that resemble the correlation patterns of simultaneous EEG/fMRI recordings. However, the nature of these BOLD oscillations and their relations to EEG activity is still poorly understood. One hypothesis is that the subunits constituting a specific RSN may be coordinated by different EEG rhythms. In this study we report on evidence for this hypothesis. The BOLD correlates of global EEG synchronization (GFS) in the alpha frequency band are located in brain areas involved in specific RSNs, e.g. the 'default mode network'. Furthermore, our results confirm the hypothesis that specific RSNs are organized by long-range synchronization at least in the alpha frequency band. Finally, we could localize specific areas where the GFS BOLD correlates and the associated RSN overlap. Thus, we claim that not only the spectral dynamics of EEG are important, but also their spatio-temporal organization.

BackgroundThe role of the language network in the pathophysiology of formal thought disorder has yet to be elucidated.AimsTo investigate whether specific grey-matter deficits in schizophrenic formal thought disorder correlate with resting perfusion in the left-sided language network.MethodWe investigated 13 right-handed patients with schizophrenia and formal thought disorder of varying severity and 13 matched healthy controls, using voxel-based morphometry and magnetic resonance imaging perfusion measurement (arterial spin labelling).ResultsWe found positive correlations between perfusion and the severity of formal thought disorder in the left frontal and left temporoparietal language areas. We also observed bilateral deficits in grey-matter volume, positively correlated with the severity of thought disorder in temporoparietal areas and other brain regions. The results of the voxel-based morphometry and the arterial spin labelling measurements overlapped in the left posterior superior temporal gyrus and left angular gyrus.ConclusionsSpecific grey-matter deficits may be a risk factor for state-related dysfunctions of the left-sided language system, leading to local hyperperfusion and formal thought disorder.

Background: Motor symptoms are frequent in schizophrenia and relevant to the diagnosis of subtypes. However, the assessment has been limited to observations recorded in scales and experimental designs. The aim of this study was to use wrist actigraphy to obtain motor activity data in 3 schizophrenia subtypes. Methods: In total, 60 patients with schizophrenia (35 paranoid, 12 catatonic, 13 disorganized) were investigated using continuous wrist actigraphy over 24 h in an inpatient setting on average 38 days after admission. Data of the wakeful hours of the day were analyzed. Results: The activity level was predicted by schizophrenia subtype and by the type of antipsychotic medication. The movement index and mean duration of uninterrupted immobility were found to be predicted only by the schizophrenia subtype. Age, gender, duration of illness and chlorpromazine equivalents did not contribute to the variance of the activity data. A MANOVA demonstrated the significant differences in the 3 parameters between schizophrenia subtypes (p = 0.001). Patients with catatonic schizophrenia had lower activity levels, a lower movement index and a longer duration of immobility than those with paranoid schizophrenia. Conclusions: Schizophrenia subtypes can be differentiated using objective measures of quantitative motor activity. The increased duration of immobility appears to be the special feature of catatonic schizophrenia.

The Frankfurter Beschwerde-Fragebogen (FBF), assessing basic symptoms (B-S), and the Scale for the Assessment of Negative Symptoms (SANS) were administered to 30 patients satisfying DSM-III-R criteria for the diagnosis of schizophrenia. Considering the relationship between BS and negative symptoms (N-S), we identified the key role of the impairment of receptive and expressive language for the correlation of these two orders of phenomena.

In visual perception of emotional stimuli, low- and high-level appraisal processes have been found to engage different neural structures. Beyond emotional facial expression, emotional prosody is an important auditory cue for social interaction. Neuroimaging studies have proposed a network for emotional prosody processing that involves a right temporal input region and explicit evaluation in bilateral prefrontal areas. However, the comparison of different appraisal levels has so far relied upon using linguistic instructions during low-level processing, which might confound effects of processing level and linguistic task. In order to circumvent this problem, we examined processing of emotional prosody in meaningless speech during gender labelling (implicit, low-level appraisal) and emotion labelling (explicit, high-level appraisal). While bilateral amygdala, left superior temporal sulcus and right parietal areas showed stronger blood oxygen level-dependent (BOLD) responses during implicit processing, areas with stronger BOLD responses during explicit processing included the left inferior frontal gyrus, bilateral parietal, anterior cingulate and supplemental motor cortex. Emotional versus neutral prosody evoked BOLD responses in right superior temporal gyrus, bilateral anterior cingulate, left inferior frontal gyrus, insula and bilateral putamen. Basal ganglia and right anterior cingulate responses to emotional versus neutral prosody were particularly pronounced during explicit processing. These results are in line with an amygdala-prefrontal-cingulate network controlling different appraisal levels, and suggest a specific role of the left inferior frontal gyrus in explicit evaluation of emotional prosody. In addition to brain areas commonly related to prosody processing, our results suggest specific functions of anterior cingulate and basal ganglia in detecting emotional prosody, particularly when explicit identification is necessary.

Spatial and temporal characteristics of lexico-semantic retrieval are frequently examined with semantic context (i.e., priming) paradigms. These paradigms measure context (i.e., priming) effects in word processing evoked by semantically related context. Besides the well-known attention-dependent N400 context effect (250 ms), recent studies demonstrate early automatic context effects in the P1-N1 time period (200 ms). However, in visual word presentation the semantic origin of these early effects remains debated. This study examined spatio-temporal activation dynamics of the early context effect as well as the modulation of the effect by differences in structure and accessibility of verbal semantics existent in abstract and concrete words. The early context effect was measured in visually displayed words that followed semantically related single-word context. Spatial and temporal aspects of the effect were analyzed by applying topographic and source analyses on the word-triggered Event Related Potentials. The early context effect was enhanced in abstract compared to concrete words as indicated by a difference in the occurrence of P1-N1 transition map and a corresponding topographic dissimilarity (116-140 ms). This concreteness-dependent modulation demonstrates the sensitivity of the early context effect to structural differences in verbal semantics. Furthermore, the topographic difference was explained by enhanced activation in the left inferior prefrontal cortex for related compared to unrelated words in addition to temporo-parietal generators recruited in both conditions. The result suggests automatic feedforward processing of context-related information in temporo-prefrontal brain regions critical to semantic analysis. Taken together our findings show that the early context effect reflects activation processes in verbal semantic memory.

Patients with schizophrenia have reduced execution functions and white matter alterations indicating cerebral disconnectivity. Here we investigated the relationship between white matter integrity and event related potentials (ERP) during a continuous performance test (CPT). Anisotropy values were correlated with the brain electrical P300 microstate duration and P300 latency associated to the NoGo- and the Go-stimuli of the CPT in 11 patients with first episode schizophrenia and 11 matched healthy controls. Both groups showed significant positive correlations of the NoGo-microstate duration with the white matter signal in the superior frontal region, the optic radiation, the posterior cingulate, and the inferolateral fascicle. In addition, patients with first episode schizophrenia had significant correlations with the right radiation and the left genu of the corpus callosum, bilateral geniculate, and the left middle and the superior temporal regions. We interpreted these findings as a sign of functional correlates of extended circuits for the active inhibition of a motor response in the visual CPT as compared to controls.

Objectives: It was found that in chronic schizophrenia patients the NoGo anteriorisation (NGA) in a cued Continuous Performance Test (CPT) was markedly reduced. Our study was performed to reproduce this result in first-episode schizophrenic patients by microstate (MS) analysis. Methods: 18 schizophrenic patients, half were medicated with antipsychotics, and 18 healthy subjects matched for gender and age were investigated with a cued CPT. Event related potentials (ERP) were recorded with 21 EEG-channels. Go trials must be answered by pressing a button. In each subject Go- and NoGo-average ERP-maps were clustered into 5 topographical MS-classes. At MS-maximum the positive centroids of the Go- and NoGo-maps and their distance, the NGA, were determined Results: In schizophrenia patients the following significant effects were found: Increase of NGA, reaction time and NoGo-latency as well as decrease of Go- and NoGo-amplitudes and NoGo-MS-duration. Beginning of NoGo-MS was retarded. The increase of NGA was not induced by antipsychotics. Conclusions: Whereas most of the P300-parameters reflecting attention are typically decreased already in first-episode schizophrenia patients, frontal function represented by the increase of NGA seems to be intact in first-episode but decreases during chronification of schizophrenia. It is discussed, whether in the initial phase of schizophrenia prevention of psychotic episodes could decrease or prevent the progression of cognitive impairment.

University Hospital of Psychiatry Bern, Bern, Switzerland (D Hubl MD, Prof W Strik MD); Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland (M Hauf MD); Department of Psychiatric Neurophysiology, University Hospital of Psychiatry Bern, Bern, Switzerland (C van Swam lic phil, Prof T Dierks MD); and Division of Neuropsychological Rehabilitation, Department of Neurology, Inselspital, University of Bern, Bern, Switzerland (Prof R Muri MD)

Motor symptoms are frequent in schizophrenia and relevant to diagnosis. They are usually assessed by clinical observation and ratings based on psychometric scales. However, investigations with quantitative measurements are rare. To understand the relationship between the objective parameters of a quantitative motor activity measurement and the items related to motor symptoms of the Positive and Negative Syndrome Scale (PANSS), 55 schizophrenia patients were studied with 24-h continuous wrist actigraphy. Activity level, movement index, and mean duration of uninterrupted immobility periods were analyzed for wakeful periods. Actigraphic parameters were strongly inter-correlated. High PANSS negative syndrome subscale scores predicted low activity levels. Single PANSS items, such as suspiciousness, hallucinatory behavior, and emotional withdrawal, contributed largely to the variance in activity level and movement index. Age, gender, medication, and duration of illness had no significant impact on the actigraphic parameters. Interestingly, correlations between the specific motor symptoms of the PANSS and the actigraphic parameters were only found as a non-significant trend. We conclude that the objectively measured quantity of movement is related to the clinically assessed negative syndrome in schizophrenia. In contrast, PANSS items related to psychomotor behavior imprecisely reflect real quantitative motor activity.

Objective NoGo-stimuli during a Continuous Performance Test (CPT) activate prefrontal brain structures such as the anterior cingulate gyrus and lead to an anteriorisation of the positive electrical field of the NoGo-P300 relative to the Go-P300, so-called NoGo-anteriorisation (NGA). NGA during CPT is regarded as a neurophysiological standard index for cognitive response control. While it is known that patients with chronic schizophrenia exhibit a significant reduction in NGA, it is unclear whether this also occurs in patients undergoing their first-episode. Thus, the aim of the present study was to determine NGA in a group of patients with first-episode schizophrenia by utilizing a CPT paradigm. Methods Eighteen patients with first-episode schizophrenia and 18 matched healthy subjects were investigated electrophysiologically during a cued CPT, and the parameters of the Go- and NoGo-P300 were determined using microstate analysis. Low resolution tomography analysis (LORETA) was used for source determination. Results Due to a more posterior Go- and a more anterior NoGo-centroid, NGA was greater in patients than in healthy controls. LORETA indicated the same sources for both groups after Go-stimuli, but a more anterior source in patients after NoGo-stimuli. In patients P300-amplitude responses to both Go- and NoGo-stimuli were decreased, and P300-latency to NoGo-stimuli was increased. After the Go-stimuli false reactions and reaction times were increased in patients. Conclusions Attention was reduced in patients with first-episode schizophrenia, as indicated by more false reactions, prolongation of reaction time, P300-latencies and by a decrease in P300-amplitude. Significantly however, the NGA and prefrontal LORETA-sources indicate intact prefrontal brain structures in first-episode schizophrenia patients. Previously described changes in this indicator of prefrontal function may be related to a progressive decay in chronic schizophrenia. Significance The results support the idea of a possible new biological marker of first episode psychosis, which may be a useful parameter for the longitudinal measurement of changing prefrontal brain function in a single schizophrenia patient.

BackgroundHallucinations are perceptions in the absence of a corresponding external sensory stimulus. However, during auditory verbal hallucinations, activation of the primary auditory cortex has been described.AimsThe objective of this study was to investigate whether this activation of the auditory cortex contributes essentially to the character of hallucinations and attributes them to alien sources, or whether the auditory activation is a sign of increased general auditory attention to external sounds.MethodThe responsiveness of the auditory cortex was investigated by auditory evoked potentials (N100) during the simultaneous occurrence of hallucinations and external stimuli. Evoked potentials were computed separately for periods with and without hallucinations; N100 power, topography and brain electrical sources were analysed.ResultsHallucinations lowered the N100 amplitudes and changed the topography, presumably due to a reduced left temporal responsivity.ConclusionsThis finding indicates competition between auditory stimuli and hallucinations for physiological resources in the primary auditory cortex. The abnormal activation of the primary auditory cortex may thus be a constituent of auditory hallucinations.

Aim This study compared matched samples of substance use disorder (SUD) patients in Swiss and United States (US) residential treatment programs and examined the relationship of program characteristics to patients’ substance use and psychosocial functioning at a 1-year follow-up. Design and Setting The study used a prospective, naturalistic design and a sample of 10 public programs in the German-speaking part of Switzerland and 15 US public treatment programs. Participants A total of 358 male patients in Swiss programs were matched on age, marital status and education with 358 male patients in US programs. A total of 160 Swiss and 329 US patient care staff members also participated. Measurement Patients completed comparable inventories at admission, discharge and 1-year follow-up to assess their substance use and psychological functioning and receipt of continuing care. Staff members reported on program characteristics and their beliefs about substance use. Findings Compared to Swiss patients, US patients had more severe substance use and psychological problems at intake and although they did not differ on abstinence and remission at follow-up, had somewhat poorer outcomes in other areas of functioning. Swiss programs were longer and included more individual treatment sessions; US programs included more group sessions and were more oriented toward a disease model of treatment. Overall, length of program, treatment intensity and 12-step orientation were associated with better 1-year outcomes for patients in both Swiss and US programs. Conclusions The sample of Swiss and US programs studied here differed in patient and treatment characteristics; however, in general, there were comparable associations between program characteristics and patients’ 1-year outcomes. These findings suggest that associations between treatment processes and patients’ outcomes may generalize from one cultural context to another.

Introduction Motor symptoms are an integral part of the clinical presentation of schizophrenia and disturbances of fine motor function are frequent. However, only limited knowledge exists on the neural correlates of fine motor skills in schizophrenia. We implemented a complex fine motor task to test associations with whole brain gray matter (GM) volume as well as cerebral blood flow (CBF). We aimed to investigate whether patients with difficulties of fine motor performance would show structural and cerebral blood flow alterations in the motor loop. Methods In total 42 schizophrenia patients (59.5% men, mean age=38.6±11.4) diagnosed according to DSM-V underwent MR-neuroimaging. All patients but four received antipsychotic treatment. Parkinsonism was assessed using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). Fine motor skills were assessed using the coin rotation task. The task is to rotate a coin (.5 swiss francs) using three fingers of the left hand (thumb, index, middle) through serial 180-degree turns as rapidly as possible. Deficits are indicated by the reduced number of half turns and coin drops. We processed structural images using standard SPM8 procedures, in particular voxel-based morphometry (VBM) toolbox. Resting state CBF was measured by arterial spin labeling (ASL). ASL data was analyzed with our custom written MATLAB programs (Federspiel et al., 2006; Walther et al., 2011). The main emphasis was to explore the effect of task performance on GM volume and CBF. Correlations of task performance (mean=10.7±4.1) and GM volume (covariates total intracranial volume and UPDRS) as well as CBF (covariate UPDRS) were calculated. A threshold of p - uncorr 0.001 (min. cluster size=17: equivalent to a map-wise false positive rate of alpha Results We found significant correlations of coin rotation scores and GM volume in the bilateral pre-supplementary motor area (pre-SMA) extending to the SMA, in the left primary motor cortex, the right superior frontal gyrus, bilateral the cerebellum and the left putamen. The pre-SMA cluster survived family wise error correction at cluster level. Significant correlations of CBF and the coin rotation scores were detected in the right SMA, the left primary motor cortex and in the right superior frontal gyrus (Area Fp1), the left inferior frontal gyrus and the right precuneus. Two clusters survived family wise error correction: right superior frontal gyrus and the left inferior frontal gyrus. Discussion Difficulties of fine motor task performance were associated with structural gray matter volume reduction in the motor loop, particularly in cortical motor control areas. In addition fine motor function in schizophrenia patients was linked with cerebral blood flow. These findings were corrected for parkinsonism. In sum, the results argue for specific alterations of the motor system in schizophrenia as source of impaired fine motor function beyond parkinsonism.

Cerebral disconnectivity due to white matter alterations in patients with chronic schizophrenia assessed by diffusion tensor imaging has been reported previously. The aim of this preliminary study is to investigate whether cerebral disconnectivity can be detected as early as the first episode of schizophrenia. Intervoxel coherence values were compared by voxel-based t test in 12 patients with first episode schizophrenia and 12 age- and gender-matched control groups. We detected 14 circumscribed significant clusters (P

We present an overview of different methods for decomposing a multichannel spontaneous electroencephalogram (EEG) into sets of temporal patterns and topographic distributions. All of the methods presented here consider the scalp electric field as the basic analysis entity in space. In time, the resolution of the methods is between milliseconds (time-domain analysis), subseconds (time- and frequency-domain analysis) and seconds (frequency-domain analysis). For any of these methods, we show that large parts of the data can be explained by a small number of topographic distributions. Physically, this implies that the brain regions that generated one of those topographies must have been active with a common phase. If several brain regions are producing EEG signals at the same time and frequency, they have a strong tendency to do this in a synchronized mode. This view is illustrated by several examples (including combined EEG and functional magnetic resonance imaging (fMRI)) and a selective review of the literature. The findings are discussed in terms of short-lasting binding between different brain regions through synchronized oscillations, which could constitute a mechanism to form transient, functional neurocognitive networks.

Objective In EEG/MEG experiments, increasing the number of sensors improves the spatial resolution of the results. However, the standard statistical methods are inappropriate for these multivariate, highly correlated datasets. We introduce a procedure to identify spatially extended scalp fields that correlate with some external, continuous measure (reaction-time, performance, clinical status) and to test their significance. Methods We formally deduce that the channel-wise covariance of some experimental variable with scalp field data directly represents intracerebral sources associated with that variable. We furthermore show how the significance of such a representation can be tested with resampling techniques. Results Simulations showed that depending on the number of channels and subjects, effects can be detected already at low signal to noise ratios. In a sample analysis of real data, we found that foreign-language evoked ERP data were significantly associated with foreign-language proficiency. Inverse solutions of the extracted covariances pointed to sources in language-related areas. Conclusions Covariance mapping combined with bootstrapping methods has high statistical power and yields unique and directly interpretable results. Significance The introduced methodology overcomes some of the ‘traditional’ statistical problems in EEG/MEG scalp data analysis. Its application can improve the reproducibility of results in the field of EEG/MEG.

This study explored transient changes in EEG microstates and spatial Omega complexity associated with changes in multistable perception. 21-channel EEG was recorded from 13 healthy subjects viewing an alternating dot pattern that induced illusory motion with ambiguous direction. Baseline epochs with stable motion direction were compared to epochs immediately preceding stimuli that were perceived with changed motion direction ('reference stimuli'). About 750 ms before reference stimuli, Omega complexity decreased as compared to baseline, and two of four classes of EEG microstates changed their probability of occurrence. About 300 ms before reference stimuli, Omega complexity increased and the previous deviations of EEG microstates were reversed. Given earlier results on Omega complexity and microstates, these sub-second EEG changes might parallel longer-lasting fluctuations in vigilance. Assumedly, the discontinuities of illusory motion thus occur during sub-second dips in arousal, and the following reconstruction of the illusion coincides with a state of relative over-arousal.

In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.

Previous MRI-volumetric studies in schizophrenic psychoses have demonstrated more or less pronounced volume reductions of the hippocampus in patients. Correspondingly, neuropathological examinations on the brains of schizophrenics showed diverse structural changes of the hippocampus. Employing a high-resolution 3D-MPRAGE sequence, we found volume reductions in most hippocampal subregions of schizophrenic patients, which, however, did not reach significant levels. An analysis of co-registered diffusion tensor imaging (DTI) data revealed significant alterations of the inter-voxel coherences in single hippocampal subdivisions of these patients, supporting the assumption of characteristic microstructural tissue changes relevant for the pathogenesis of schizophrenic psychoses. Our results argue for the usage of additional MRI modalities like DTI in order to detect subtle regional alterations of hippocampal structure in schizophrenics.

The precise role of the fusiform face area (FFA) in face processing remains controversial. In this study, we investigated to what degree FFA activation reflects additional functions beyond face perception. Seven volunteers underwent rapid event-related functional magnetic resonance imaging while they performed a face-encoding and a face-recognition task. During face encoding, activity in the FFA for individual faces predicted whether the individual face was subsequently remembered or forgotten. However, during face recognition, no difference in FFA activity between consciously remembered and forgotten faces was observed, but the activity of FFA differentiated if a face had been seen previously or not. This demonstrated a dissociation between overt recognition and unconscious discrimination of stimuli, suggesting that physiological processes of face recognition can take place, even if not all of its operations are made available to consciousness.

The aim of the present study was to investigate prefrontal brain function and cognitive response control in patients with personality disorders who either suffered or did not suffer from psychopathology related to attention deficit hyperactivity disorder (ADHD) during childhood. For this purpose, 36 psychiatric out-patients with personality disorders--24 of whom showed ADHD-related psychopathology during childhood assessed by the German short form of the Wender Utah Rating Scale--and 24 healthy controls were investigated electrophysiologically by means of a cued Go-NoGo task (Continuous Performance Test). Topographical analyses were conducted to individually quantify the NoGo anteriorisation (NGA), a neurophysiological correlate of prefrontal response control that has been suggested to reflect activation of the anterior cingulate cortex. ADHD patients exhibited a significantly reduced mean NGA and diminished amplitudes of the Global Field Power, as well as a reduced increase of fronto-central P300 amplitudes, in NoGo-trials compared with the healthy controls, whereas patients with personality disorders alone did not differ from the control group in any of the electrophysiological parameters. The results indicate that ADHD-related psychopathology is associated with prefrontal brain dysfunction, probably related to processes of response inhibition and/or cognitive response control.

Linking the working brain with psychological and psychopathological processes requires an understanding of the complex electro-chemical neuronal activation patterns which underpin mental activities dependent on topographical interactions at systems level. This may be achieved by virtue of the fine temporal resolution of neurophysiological methods which assess summed electrical field potentials. The electroencephalogram (EEG) and event-related potential (ERP) methodologies are no longer simply used to exclude organic pathology. Here, evidence is reviewed showing that cognitive ERPs are related to psychiatric subdiagnoses, risk factors, symptom dimensions and prognosis. In addition there is a renaissance in applications and analysis of EEG rhythms including microstates, coherent oscillations, current source analysis, and composite measures of complexity and connectivity between neurophysiological networks, all of which hold promise for the future. Autonomic findings are also documented. The review covers the schizophrenia spectrum, affective disorders, anxiety disorders and dementia.

Disturbances of the motor and sensory system as well as an alteration of the preparation of movements have been reported to play a role in the pathogenesis of dystonias. However, it is unclear whether higher aspects of cortical – like cognitive – functions are also involved. Recently, the NoGo-anteriorization (NGA) elicited with a visual continuous performance test (CPT) during recording of a 21-channel electroencephalogram has been proposed as an electrophysiological standard-index for cognitive response control. The NGA consists of a more anterior location of the positive area of the brain electrical field associated with the inhibition (NoGo-condition) compared with that of the execution (Go-condition) of a prepared motor response in the CPT. This response control paradigm was applied in 16 patients with writer’s cramp (WC) and 14 age matched healthy controls. Topographical analysis of the associated event-related potentials revealed a significant (P < 0.05) NGA effect for both patients and controls. Moreover, patients with WC showed a significantly higher global field power value (P < 0.05) in the Go-condition and a significantly higher difference-amplitude (P < 0.05) in the NoGo-condition. A source location analysis with the low resolution electromagnetic tomography (LORETA) method demonstrated a hypoactivity for the Go-condition in the parietal cortex of the right hemisphere and a hyperactivity in the NoGo-condition in the left parietal cortex in patients with WC compared with healthy controls. These results indicate an altered response control in patients with WC in widespread cortical brain areas and therefore support the hypothesis that the pathogenesis of WC is not restricted to a pure sensory-motor dysfunction.

between childhood trauma and psychosis, or if childhood abuse impacts on psychosis risk indirectly by increasing the individuals’ social isolation. Methods: Data on 227 first-presentation psychosis cases and 199 unaffected population-based controls was drawn from the Childhood Adversity and Psychosis (CAPsy) Study. Using the Childhood Experience of Care and Abuse Interview (CECA), information was obtained on early adversity before the age of 17 (psychological abuse, physical abuse, bullying victimisation) and perceived social support in childhood (from adults, from peers, and perceived loneliness). Data was analysed using mediational analyses and logistic regression (and tested for interaction on an additive scale using Interaction Contrast Ratios). Results: Compared with controls, cases more commonly reported experiences of severe bullying victimisation (adjusted odds ratio [aOR] 2.69, 95% Confidence Interval [CI] 0.96–7.51), and severe psychological (aOR 6.27, 95% CI 2.48–15.84) and physical (aOR 1.69, 95% CI 0.91–3.11) abuse. In addition, cases were approximately two times more likely than controls to report feeling lonely (aOR 2.36, 95% CI 1.41–3.97), and to having low support from adults (aOR 2.17, 95% CI 1.31–3.59) and peers (aOR 2.15, 95% CI 1.31–3.53). There was no strong evidence that social support modified these relationships, which may be due to limited power to test interaction effects at this point. There was, however, strong evidence that around 35–40% of the total effect of severe psychological abuse, and 50–58% of the total effect of severe physical abuse, on psychosis was via pathways through low perceived support from adults (indirect effects: psychological abuse – aOR 2.75, 95% CI 1.07–7.09; physical abuse – aOR 1.91, 95% CI 1.08–3.37), low perceived support from peers (indirect effects: psychological abuse – aOR 2.96, 95% CI 0.98–8.94; physical abuse – aOR 1.67, 95% CI 1.02–2.75), and perceived loneliness (indirect effects: psychological abuse – aOR 2.47, 95% CI 1.07–5.69; physical abuse – aOR 1.79, 95% CI 1.04–3.08). In addition, 69% of the total effect of severe bullying victimisation on psychosis was via pathways through feelings of loneliness in childhood (indirect effect: aOR 7.01, 95% CI 1.51–32.52). Discussion: This is the first study to show that the effects of abuse in childhood on psychosis appear to be mainly mediated through low levels of perceived childhood support. Additionally, high levels of support from adults or peers may be protective in those who experience severe bullying victimisation. These findings have significant implications for the intervention of psychosis.