Martin Brunovský

Electroencephalographic Spectral and Coherence Analysis of Ketamine in Rats: Correlation with Behavioral Effects and Pharmacokinetics

Aims: This study was designed to evaluate the changes in EEG power spectra and EEG coherence in a ketamine model of psychosis in rats. Analyses of behavioral measurements – locomotion and sensorimotor gating – and the pharmacokinetics of ketamine and norketamine were also conducted. Methods: Ketamine and norketamine levels in rat sera and brains were analyzed by gas chromatography-mass spectrometry after ketamine 30 mg/kg (i.p.). Ketamine 9 and 30 mg/kg (i.p.) were used in the behavioral and EEG experiments. Locomotor effects in an open field test and deficits in prepulse inhibition of acoustic startle reaction (PPI ASR) were evaluated in the behavioral experiments. EEG signals were simultaneously recorded from 12 implanted active electrodes; subsequently, an EEG power spectral and coherence analysis was performed. Results: Ketamine had a rapid penetration into the brain; the peak concentrations of the drug were reached within 15 min after administration. Ketamine induced marked hyperlocomotion and deficits in the PPI ASR. EEG spectral analysis mainly showed increases in EEG power as well as coherence. These were most robust at 10–15 min after the administration and influenced all parts of the spectrum with ketamine 30 mg/kg. Conclusions: Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence. The maximum levels of change correlated with the kinetics of ketamine.

EEG source analysis in obsessive–compulsive disorder

OBJECTIVE The goal of this study was to assess the activity of intracortical EEG sources in patients with OCD. METHODS We compared resting state EEG from 50 OCD patients and 50 matched controls using standardized low-resolution electromagnetic tomography (sLORETA) and normative independent component analysis (NICA). Data were analyzed with 1 Hz frequency resolution. Group ICA was used to separate seven independent components from the control group data. The resulting weights and norms served to derive the same components from the OCD group and to compare their power with controls. RESULTS In OCD, sLORETA indicated low-frequency power excess (2-6 Hz) in the medial frontal cortex, whereas group ICA showed increased low-frequency power in a component reflecting the activity of subgenual anterior cingulate, adjacent limbic structures and to a lesser extent also of lateral frontal cortex. CONCLUSIONS Both methods provided evidence for medial frontal hyperactivation in OCD. SIGNIFICANCE Our study is the first to use normative ICA in a clinical sample and indicates its potential utility as a diagnostic tool. The findings provide consistent results based on EEG source localization in OCD and are of practical interest for therapeutic interventions.

Prediction of treatment response and the effect of independent component neurofeedback in obsessive-compulsive disorder: a randomized, sham-controlled, double-blind study.

Aims: The goal of this study was to assess the effect of independent component neurofeedback (NFB) on EEG and clinical symptoms in patients with obsessive-compulsive disorder (OCD). Subsequently, we explored predictors of treatment response and EEG correlates of clinical symptoms. Methods: In a randomized, double-blind, parallel design, 20 inpatients with OCD underwent 25 sessions of NFB or sham feedback (SFB). NFB aimed at reducing EEG activity in an independent component previously reported abnormal in this diagnosis. Resting-state EEG recorded before and after the treatment was analyzed to assess its posttreatment changes, relationships with clinical symptoms and treatment response. Results: Overall, clinical improvement in OCD patients was not accompanied by EEG change as assessed by standardized low-resolution electromagnetic tomography and normative independent component analysis. Pre- to posttreatment comparison of the trained component and frequency did not yield significant results; however, in the NFB group, the nominal values at the downtrained frequency were lower after treatment. The NFB group showed significantly higher percentage reduction of compulsions compared to the SFB group (p = 0.015). Pretreatment higher amount of delta (1-6 Hz) and low alpha oscillations as well as a lower amount of high beta activity predicted a worse treatment outcome. Source localization of these delta and high beta oscillations corresponded with previous EEG resting-state findings in OCD patients compared to healthy controls. Conclusion: Independent component NFB in OCD proved useful in percentage improvement of compulsions. Based on our correlation analyses, we hypothesize that we targeted a network related to treatment resistance.

Physical Comorbidities in Depression Co-Occurring with Anxiety: A Cross Sectional Study in the Czech Primary Care System

Comorbidities associated with depression have been researched in a number of contexts. However, the epidemiological situation in clinical practice is understudied, especially in the post-Communist Central and Eastern Europe region. The aim of this study was to assess physical comorbidities in depression, and to identify whether there are increased odds of physical comorbidities associated with co-occurring depressive and anxiety disorders. Data on 4264 patients aged 18–98 were collected among medical doctors in the Czech Republic between 2010 and 2011. Descriptive statistics were calculated and multiple logistic regressions were performed to assess comorbidities among patients with depressive disorder. There were 51.29% of those who have a physical comorbidity, and 45.5% of those who have a comorbid anxiety disorders among patients treated with depression in Czech primary care. Results of logistic regressions show that odds of having pain, hypertension or diabetes mellitus are particularly elevated at those who have co-occurring depressive and anxiety disorder. Our findings demonstrate that comorbidities associated with depressive disorders are highly prevalent in primary health care practice, and that physical comorbidities are particularly frequent among those with co-occurring depressive and anxiety disorders.

Standardized low-resolution electromagnetic tomography in obsessive-compulsive disorder--a replication study.

Previous EEG source localization studies in obsessive-compulsive disorder (OCD) reported ambiguous results. The reason probably lies in different OCD samples included in the studies - obsessive-compulsive subjects selected based on a psychopathology questionnaire (the Symptom Checklist - Revised), drug-naïve OCD cases or patients with a long-term disorder. This study was conceived as a replication of our previous research on OCD population coming to treatment in Prague Psychiatric Centre [9]. We included 50 OCD patients (8 drug-free and 42 medicated with SSRIs) and 50 healthy controls. All subjects were different from those enrolled in the previous study. Resting state EEG was analyzed in 8 frequency bands as well as with 1 Hz frequency resolution using the standardized low-resolution electromagnetic tomography (sLORETA). In OCD, sLORETA indicated low-frequency power excess at 2 and 3 Hz in the cingulate gyrus with maximal t-values in Brodmann area 24. The low-frequency activity was unrelated to the severity of clinical symptoms and illness duration but delta power in the right orbitofrontal cortex positively correlated with age of OCD onset. Our results confirm previous finding of the low-frequency excess in the cingulate gyrus in OCD and document the essential role of delta frequencies. Delta activity in the cingulate gyrus is negatively associated with reward-signalling dopamine release in the ventral striatum and increases in states connected with a need for reinforcement. Thus, delta activity could reflect a repetitive need to perform compulsive behaviour in OCD patients.

The effect of ((−)-2-oxa-4-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), an mGlu2/3 receptor agonist, on EEG power spectra and coherence in ketamine model of psychosis

In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist LY379268 on changes in EEG power spectra and coherence in the ketamine model of psychosis. In order to use behaviorally active drug doses, experiments detecting changes in locomotor activity and sensorimotor gating were also conducted. In EEG experiments, adult male Wistar rats were injected with ketamine 30 mg/kg i.p. and LY379268 3 mg/kg i.p. Cortical EEG was recorded from twelve (2 × 6) electrodes placed homolaterally on each hemisphere. To avoid interference with the behavioral hyperactivity of ketamine challenge, the behavioral activity of animals was simultaneously registered at the time of recording. Subsequent power spectral and coherence analyses were assessed in epochs corresponding to behavioral inactivity. Analysis of segments with behavioral activity compared to inactivity was also performed. The effects of LY379268 3 mg/kg i.p. on the deficits in sensorimotor processing and on hyperlocomotion induced by ketamine were evaluated in the test of prepulse inhibition of acoustic startle reaction (PPI ASR) and in the open field. LY379268 reversed the ketamine-induced hyperlocomotion but had no effect on ketamine-induced PPI deficits. In EEG epochs corresponding to behavioral inactivity ketamine decreased the power in the delta band, induced a power increase in the high frequency bands and globally decreased EEG coherence. Pretreatment with the LY379268 completely reversed the ketamine-induced power increase in high frequency bands and had a partial effect on EEG coherence. LY379268 alone induced a decrease of beta, high beta and low-gamma power, and an increase in coherence in high frequency bands. Additional analysis revealed that behavioral activity increases power as well as coherence in most frequency bands. In conclusion, agonism of mGlu2/3 receptors was effective in reversing most of the changes induced by ketamine, however due to the lack of effectiveness on PPI deficits its potential antipsychotic properties remain disputable.

Latent Schizencephaly With Psychotic Phenotype or Schizophrenia With Schizencephaly? A Case Report and Review of the Literature

Objectives. Although schizencephaly belongs to the class of neurodevelopmental disorders, which are a well-known predisposing factor for psychosis, there is a lack of relevant studies and diagnostic guidelines on this relationship. Method. A case report of first-episode psychosis with persistent negative symptoms associated with schizencephaly is described and compared with 7 other cases found in the literature. Results. We found perinatal pathology, cognitive deficit, and EEG abnormality in a patient with atypical initial symptoms of psychosis such as olfactory hallucinations. Abnormal EEG findings (left frontal spikes and frontal intermittent rhythmic delta activity) called for magnetic resonance imaging, which revealed left parieto-occipital closed-lip schizencephaly. The patient exhibited a partial response to low-dose amisulpride treatment. Conclusion. We conclude that schizencephaly in our patient was at first asymptomatic and later developed into clinically manifest schizophrenia-like disorder. Both magnetic resonance imaging and EEG were essential tools for establishing this diagnosis.

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40–60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

Contents Vol. 67, 2013

R. Calati, Bologna A. Drago, Naples G. Erdmann, Berlin A. Fischer, Göttingen J.M. Ford, San Francisco, Calif. S. Galderisi, Naples M. Hatzinger, Solothurn K. Hirata, Mibu M. Kato, Osaka J. Kindler, Bern T. Koenig, Bern D. Lehmann, Zürich M. Maes, Geelong, Vic. L. Mandelli, Bologna P. Monteleone, Naples G. Okugawa, Osaka G.N. Papadimitriou, Athens M. Popoli, Milano M. Reuter, Bonn G. Ruigt, Oss J.K. Rybakowski, Poznan F. Rybakowski, Warzaw/Poznan F. Schneider, Aachen R. Schwarting, Marburg D. Souery, Brussels A. Steiger, Munich S. Walther, Bern K. Watanabe, Tokyo P. Willner, Swansea M. Yoshimura, Osaka Associate Editors

Contents Vol. 63, 2011

A. Drago, Naples G. Erdmann, Berlin A. Fischer, Göttingen J.M. Ford, San Francisco, Calif. S. Galderisi, Naples M. Hatzinger, Solothurn U. Hegerl, Leipzig K. Hirata, Mibu M. Kato, Osaka J. Kornhuber, Erlangen D. Lehmann, Zürich P. Monteleone, Naples G. Okugawa, Osaka G.N. Papadimitriou, Athens M. Popoli, Milano M. Reuter, Bonn F. Rösler, Marburg G. Ruigt, Oss J.K. Rybakowski, Poznan F. Schneider, Aachen R. Schwarting, Marburg M. Shigeta, Tokyo D. Souery, Brussels A. Steiger, Munich P. Willner, Swansea Associate Editors