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.

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in risperidone patients versus antipsychotic-naive subjects may relate to risperidone's different pharmacodynamic mechanism.

QEEG changes during switch from depression to hypomania/mania: a case report.

BACKGROUND: QEEG cordance and low-resolution electromagnetic tomography (LORETA) are relatively new applications of QEEG. Four small-scale studies have shown that decreases of QEEG prefrontal theta cordance after the first week on new antidepressants predict clinical response to treatment in patients with unipolar depression. METHODS: We calculated prefrontal theta cordance and changes in 3D distribution of brain electrical activity using LORETA in the case of a 54-year old man experiencing his third depressive episode. RESULTS: We did not detect a decrease of prefrontal theta cordance after one week of new treatment and the patient did not respond to this therapy after four weeks. However, we observed a decrease of prefrontal theta cordance after the first week of clomipramine therapy. Manic symptoms emerged after two weeks of clomipramine treatment. A decrease of prefrontal theta cordance preceded the clomipramine induced switch to hypomania during the next episode of depression also. LORETA before and during clomipramine therapies detected a significant increase of theta in the right postcentralis gyrus in the parietal lobe, and a borderline increase of alfa2 in the right middle frontal gyrus. DISCUSSION: In a patient with bipolar spectrum disorder we found that a treefold change in theta prefrontal cordance preceded mood changes in a similar way as in patients with unipolar depression. We speculate that the changes detected by LORETA can attributed to the anticholinergic activity of clomipramine and the specific effects of a mood switch. Our data suggest that the new applications of QEEG can be sensitive to mood changes and have potential in bipolar disorder research.

Effect of low-frequency rTMS on electromagnetic tomography (LORETA) and regional brain metabolism (PET) in schizophrenia patients with auditory hallucinations.

BACKGROUND: Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (

18FDG PET in hallucinating and non-hallucinating patients.

OBJECTIVE: The aim of the study was to detect whether the abnormal regional brain activity correlates with auditory verbal hallucination-proneness (AVH) in a group of patients with schizophrenia and schizophrenia-related psychoses. METHODS: 15 patients with prominent AVH (score for hallucination intensity--item 3 in the PANSS > or =4) and 15 control patients without AVH (item 3 PANSS score < or =2) underwent 18FDG positron emission tomography at rest. RESULTS: SPM group analysis revealed an increased uptake of 18FDG in the right middle frontal gyrus (BA46) in subjects with high verbal hallucination score compared to non-hallucinating patients (p<0.001, uncorrected). Activation in BA46 positively correlated with the intensity of hallucinations (Spearman r=0.57; p<0.001). CONCLUSIONS: The observed functional recruitment of the right prefrontal cortex in subjects with high hallucination score may reflect impairment in the integration of intended actions and sensory feedback resulting in misattribution of internal events to an external source. This mechanism may form the cognitive basis for AVH.

Regional brain metabolism as the predictor of performance on the Trail Making Test in schizophrenia. A 18FDG PET covariation study.

OBJECTIVES: With the aim to indicate the functional anatomical substrate of cognitive dysfunction in schizophrenia we evaluated the relationship between resting brain metabolism and performance on the Trail Making Test (TMT). As the prerequisite analysis we compared the performance in Part A and B of the TMT between schizophrenic patients and controls. Resting brain metabolism was investigated by (18)FDG positron emission tomography (PET) as the probe for the relative regional synaptic strength and density. METHODS: (18)FDG PET data were analyzed by SPM99 with TMT A and B as the covariate (p< or =0.001). RESULTS: Schizophrenic patients (N=42) had worse performance in both TMT A and B compared to controls (N=42). In schizophrenic subjects (18)FDG PET did not predict the performance on Part A (psychomotor speed) but predicted that for Part B (set-shifting and flexibility) of the TMT. The (18)FDG uptake in the superior, middle and inferior frontal gyruses bilaterally was associated with better performance in the TMT B. The negative covariation between 18FDG uptake and time spent in the TMT B was detected in the temporal and parietal cortices, pre- and postcentral gyruses, precuneus limbic regions (anterior cingulate, uncus) and the pons. CONCLUSIONS: Our data indicate that hypometabolism in the frontal lobes and hypermetabolism in the temporo-parieto-limbic regions is the neurobiological basis for deficient TMT B performance in schizophrenia.