Resting-state EEG in schizophrenia: auditory verbal hallucinations are related to shortening of specific microstates.

OBJECTIVE: Abnormal perceptions and cognitions in schizophrenia might be related to abnormal resting states of the brain. Previous research found that a specific class (class D) of sub-second electroencephalography (EEG) microstates was shortened in schizophrenia. This shortening correlated with positive symptoms. We questioned if this reflected positive psychotic traits or present psychopathology. METHODS: Resting-state EEGs of frequently hallucinating patients, indicating on- and offset of hallucinations by button press, were analyzed. Microstate class D duration was related to spontaneous within-subject fluctuations of auditory hallucinations. RESULTS: Microstate D was significantly shorter in periods with hallucinations. CONCLUSIONS: Microstates of class D resemble topographies associated with error monitoring. Its premature termination may facilitate the misattribution of self-generated inner speech to external sources during hallucinations. SIGNIFICANCE: These results suggest that microstate D represents a biological state marker for hallucinatory experiences.

Elevated bilirubin in acute and transient psychotic disorder.

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.

The influence of emotion clarity on emotional prosody identification in paranoid schizophrenia.

BACKGROUND: Identification of emotional facial expression and emotional prosody (i.e. speech melody) is often impaired in schizophrenia. For facial emotion identification, a recent study suggested that the relative deficit in schizophrenia is enhanced when the presented emotion is easier to recognize. It is unclear whether this effect is specific to face processing or part of a more general emotion recognition deficit. METHOD: We used clarity-graded emotional prosodic stimuli without semantic content, and tested 25 in-patients with paranoid schizophrenia, 25 healthy control participants and 25 depressive in-patients on emotional prosody identification. Facial expression identification was used as a control task. RESULTS: Patients with paranoid schizophrenia performed worse than both control groups in identifying emotional prosody, with no specific deficit in any individual emotion category. This deficit was present in high-clarity but not in low-clarity stimuli. Performance in facial control tasks was also impaired, with identification of emotional facial expression being a better predictor of emotional prosody identification than illness-related factors. Of those, negative symptoms emerged as the best predictor for emotional prosody identification. CONCLUSIONS: This study suggests a general deficit in identifying high-clarity emotional cues. This finding is in line with the hypothesis that schizophrenia is characterized by high noise in internal representations and by increased fluctuations in cerebral networks.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field.

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

[Possible genetic link between Darier's disease and depression. Review of the literature and case history]. / Morbus Darier und Depression - besteht eine genetische Verbindung? Ubersicht und klinischer Fall.

Darier's disease is a rare, inherited autosomal dominant skin disorder caused by a mutation in the sarcoendoplasmatic reticulum calcium transporter (SERCA)-2-gene. In a number of pedigrees, Darier's disease closely relates with affective disorder. The most likely hypothesis for this is a susceptibility gene for affective disorder near the SERCA-2-gene. A 6.5-megabase region could be identified as a susceptibility locus. This region constitutes a susceptability locus also in affective disorder without Darier's disease. The underlying gene has not yet been identified.

Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling.

Functional magnetic resonance imaging (fMRI) is presently either performed using blood oxygenation level-dependent (BOLD) contrast or using cerebral blood flow (CBF), measured with arterial spin labeling (ASL) technique. The present fMRI study aimed to provide practical hints to favour one method over the other. It involved three different acquisition methods during visual checkerboard stimulation on nine healthy subjects: 1) CBF contrast obtained from ASL, 2) BOLD contrast extracted from ASL and 3) BOLD contrast from Echo planar imaging. Previous findings were replicated; i) no differences between the three measurements were found in the location of the activated region; ii) differences were found in the temporal characteristics of the signals and iii) BOLD has significantly higher sensitivity than ASL perfusion. ASL fMRI was favoured when the investigation demands for perfusion and task related signal changes. BOLD fMRI is more suitable in conjunction with fast event related design.

Brain connectivity at different time-scales measured with EEG.

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.

[Phytotherapeutic drugs in psychiatry]. / Phytotherapeutika in der Psychiatrie.

During recent years, the use of phytotherapeutics in psychiatry has gained enormous significance. The present paper reviews current scientific data on the most important herbal substances including St. John's wort, kava, valerian, and gingko. Although psychotropic phytotherapeutics have been shown to be partly effective in some psychiatric disorders, they cannot generally be recommended as an alternative to conventional medicaments because sufficient data concerning their efficacy, differentiated indication, and safety profile are still missing. Psychiatric patients treated with herbal drugs need intensive medical advice and supervision.

Changes of the brain electrical fields during the continuous performance test in attention-deficit hyperactivity disorder-boys depending on methylphenidate medication.

OBJECTIVE: The continuous performance test (CPT) is successfully applied to evaluate attentional performance in attention-deficit hyperactivity disorder (ADHD)-children. The aim of the present study was to investigate the changes of the topographic P300-features in relation to methylphenidate-medication and to different attentional processes in primer- and distractor-conditions. METHODS: Twenty-one-channel-ERPs of 17 ADHD-boys were analyzed with reference-independent methods. Four quasi stable microstates within the time frames of conventional P100, P200, P3a and P3b components were identified by means of a data-driven segmentation procedure. RESULTS: In segment 3 topographical assessment yielded a significant occipital and right-shift of the positive centroid, longer centroid distance and higher amplitudes in primer- than in distractor conditions. MPH increased the amplitude and distance in primer and distractor-condition, without changing the topography. In segment 4 the electric field strength of distractor-conditions collapsed, whereas the primer condition showed a strong fronto-parietally oriented potential-field. There was a tendency to higher amplitudes due to MPH-medication. CONCLUSIONS: These results indicate a robust neurophysiologic differentiation of cognitive processes. MPH activates an early (P3a) covert attention process indicated by increased amplitudes and centroid. No effects were seen in later processes. Based on these effects, we propose to use the amplitude- and distance-increase in microstate 3 as an indicator of MPH efficacy in ADHD-boys.

Test-retest reliability of electrophysiological parameters related to cognitive motor control.

Previously, the continuous performance test was demonstrated to elicit distinct electrophysiological correlates of cognitive response during execution (Go) and inhibition (NoGo) of an anticipated motor response. A robust method for topographical quantification of these brain electrical microstates has been established recently. Test reliability is crucial to allow application in the assessment of neuropsychiatric disorders. The present study evaluates the reliability of the Go and NoGo centroid locations as well as the NoGo anteriorisation (NGA) in 23 healthy individuals. Our results show supreme test-alternate retest reliabilities of Pearson's product moment correlations and intraclass correlation coefficients of r> or =0.63 (P< or =0.001) for these parameters which assert a quality well within the range reported for those of other electrophysiological standard paradigms. Go and NoGo centroid locations as well as the NGA are, therefore, reliable correlates of prefrontal motor control and may contribute to the understanding of disorders with allied impairments.

The neurophysiological meaning of auditory P300 in subtypes of schizophrenia.

Event-related potentials are a powerful tool to investigate the real-time course of brain electrical mass activation during cognitive processing. In several psychiatric disorders, differences compared to healthy subjects have been reliably described. The specificity and the pathophysiological meaning of the findings were unclear in most studies, however. This review summarizes methodological aspects and findings, in healthy subjects and psychiatric patients, of investigations based on the auditory oddball paradigm, which evokes the P300 component of event-related potentials. Recent convergent results from P300 and brain imaging studies allowed the interpretation of P300 findings in psychotic disorders in terms of different specific and meaningful neurophysiological disturbances. Namely, core schizophrenia is characterized by a left-temporal dysfunction associated with deficits in verbal processing. Acute remitting schizophrenia-like psychoses (cycloid psychosis, ICD-10 F23), on the other hand, show normal hemispheric balance but consistent signs of cerebral hyperarousal. Recent studies further indicate that the drive for action of manic patients does not rely on over-excitation but rather on frontal disinhibition. The findings may help to further advance the understandings and sub-grouping of functional psychoses based on pathophysiological mechanisms.

Cognitive response control in writer's cramp.

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.

Reduced frontal functional asymmetry in schizophrenia during a cued continuous performance test assessed with near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) allows noninvasive, in vivo measurement of changes in the concentrations of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in brain tissue based on their distinctive optical properties. A previous NIRS investigation on healthy subjects (Fallgatter and Strik 1997) found indications of right frontal activation during a Continuous Performance Test (CPT) that are consistent with results from positron emission tomography (PET) and event-related potentials studies. The indications consisted of right frontal blood oxygenation changes, consistent with a hemodynamic response, along with a significant left frontal increase in HHb. The current study investigated whether this characteristic lateralized frontal NIRS activation pattern was present in a group of nine schizophrenia patients during the execution of a CPT. In contrast to the previous study, no overall or hemispheric activation effects were found in the schizophrenia subjects. Direct comparison of the results of the two studies confirmed group differences, with a lack of lateralized activation in schizophrenia patients. Furthermore, a trend of higher left/right HHb ratios at rest and during activation was found in patients with schizophrenia. The finding is interpreted as a sign of reduced specific lateralized frontal reactivity, possibly based on a left hemisphere functional deficit.

Anxiety as a primary symptom in cycloid psychosis.

Psychotic anxiety has not been systematically included in standard psychopathologic and diagnostic literature, presumably because anxiety is implicitly perceived to be an emphatically comprehensible consequence of the cognitive symptoms of psychosis. This review gives an overview of neurophysiologic studies that indicate different pathogenic mechanisms for different types of psychosis. Convergent and complementary structural and functional imaging findings, biochemical and neuropsychological data allow conjecture as to neurophysiologic-psychopathologic links in cycloid psychosis. Intriguing results suggest that in cycloid psychosis, a generalized hyperasousal related to the tonus of the noradrenergic system may be the basic disturbance causing the delusionary and perceptual psychotic distortions. The findings are specific for cycloid psychoses, which are diagnosed as polymorphous psychosis in the International Classification of Diseases and Related Health Problems, 10th Edition. Furthermore, these findings are consistent with the author's hypothesis that the emotional derailment is the primary disturbance in cycloid psychosis (anxiety-elation). In contrast, cognitive disturbances are secondary and remit after the exceptional emotional state is rebalanced.

EEG signs of vigilance fluctuations preceding perceptual flips in multistable illusionary motion.

This EEG study was performed to clarify the time course of brain electrical events and possible vigilance changes associated with perceptual flips during multistable perception. 13 healthy subjects (28.5 3.8 years) were recorded with a 21-channel digital EEG during a stroboscopic alternative motion paradigm implying illusionary motion with ambiguous direction. Perceptual flips were preceded by a significant decrease of EEG frequencies, and followed by a significant frequency increase with a trend to overshoot. EEG slowing is a reliable sign of vigilance decrease and can be related to thalamic deactivation. This is consistent with a recent fMRI study, which showed thalamic deactivation associated with perceptual flips. The study added important chronological information about this phenomenon and allows the conclusion that reduced vigilance facilitates perceptual discontinuities during multistable perception.

The NoGo-anteriorization as a neurophysiological standard-index for cognitive response control.

Event related potentials (ERPs) during the Go- and the NoGo-condition of the Continuous Performance Test (CPT) were applied to investigate the neurophysiological basis of cognitive response control. These conditions of the test represent the execution and the inhibition of an anticipated motor response. In a previous study, the comprehensive spatial analysis of the ERPs allowed to define a parameter which robustly reflected the anteriorization of the positive P300 field area during the NoGo- compared to the Go-condition (NoGo-anteriorisation, NGA). The result was found consistently in all investigated subjects. The present study replicated the finding in 27 healthy subjects without any exception. Moreover, the latencies were longer and the amplitudes showed a trend to be higher in the NoGo- compared to the Go-ERP. This is interpreted as a sign of higher processing demands in the NoGo-condition. In conclusion, the ability of the NGA to express reliably the differences of brain activity leading to execution or suppression of a prepared motor response qualifies this parameter as a topographical standard-index for cognitive response control.

Age-related changes in the brain electrical correlates of response control.

OBJECTIVES: Previously, a quantification method was validated which, on a single case basis, allows one to assess the NoGo-anteriorisation (NGA) of the positive area of long latency event-related potential (ERP) fields elicited by a cued continuous performance test (CPT). The NGA was shown to be associated with right frontal activity. The present study was conducted to investigate the influence of age and gender on this topographical index of cognitive response control. METHODS: Thirty-seven healthy controls were investigated with 21-channel recordings during the execution of a cued CPT, and ERPs of the Go and NoGo condition were obtained. The location of the positive area centroids in a P300 range and the NGA were calculated and related to age and gender by means of correlation analysis and t tests. RESULTS: The centroid locations of the brain electrical activity during the NoGo- and the Go-condition of the CPT, were both located in more anterior brain regions with increasing age (P<0.01 and P<0.1, respectively); the NGA, however, was not correlated with the subject's age. Latencies and amplitudes of the Go- and NoGo-centroids were not correlated with age. No gender differences were found. CONCLUSIONS: The study showed that age is a source of variance for the positive area centroid locations in this Go-NoGo paradigm. The NGA, on the other hand, was robust to age and gender effects. The result is interpreted as a sign of an increasing contribution of frontal brain areas to cognitive response control during lifespan. The finding is consistent with the age-related topographical changes described in acoustic oddball-paradigms and, therefore, appears to be a general topographical ERP effect.

Frontal brain activation during the Wisconsin Card Sorting Test assessed with two-channel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a new non-invasive optical technique suitable to assess the concentration changes of oxygenated (O2HB) and deoxygenated (HHB) hemoglobin in brain tissue. Previous NIRS studies showed distinct patterns of blood oxygenation changes during different cognitive tasks. In particular, bilateral frontal hypo-oxygenation was found during reading, right frontal hyper-oxygenation during the Continuous Performance Test, and left frontal hyper-oxygenation dur, ing the Verbal Fluency Test. The Wisconsin Card Sorting Test (WCST) is a neuropsychologial test which is presumed to activate prevalently the frontal lobes. This was demonstrated by lesion studies and functional imaging (single photon emission computed tomography and positron emission tomography). In the present study, a two-channel NIRS system was applied to investigate frontal brain areas of ten healthy subjects during performance of the WCST. A significant bilateral increase of O2HB in frontal brain regions without hemispheric differences was found during the WCST compared with a baseline at rest. This result indicates an enhanced perfusion of the frontal lobes consistent with local activation. The findings add further evidence that the NIRS technique is sensitive enough to detect physiological blood oxygenation changes. Furthermore, a comparison with previous studies revealed an activation pattern distinct from those observed during other cognitive tasks. It is concluded that the results reflect local responses to specific task demands of the WCST.