Abnormal oscillatory brain dynamics in schizophrenia: a sign of deviant communication in neural network?

<p>Abstract</p> <p>Background</p> <p>Slow waves in the delta (0.5–4 Hz) frequency range are indications of normal activity in sleep. In neurological disorders, focal electric and magnetic slow wave activity is generated in the vicinity of structural brain lesions. Initial studies, including our own, suggest that the distribution of the focal concentration of generators of slow waves (dipole density in the delta frequency band) also distinguishes patients with psychiatric disorders such as schizophrenia, affective disorders, and posttraumatic stress disorder.</p> <p>Methods</p> <p>The present study examined the distribution of focal slow wave activity (ASWA: abnormal slow wave activity) in116 healthy subjects, 76 inpatients with schizophrenic or schizoaffective diagnoses and 42 inpatients with affective (ICD-10: F3) or neurotic/reactive (F4) diagnoses using a newly refined measure of dipole density. Based on 5-min resting magnetoencephalogram (MEG), sources of activity in the 1–4 Hz frequency band were determined by equivalent dipole fitting in anatomically defined cortical regions.</p> <p>Results</p> <p>Compared to healthy subjects the schizophrenia sample was characterized by significantly more intense slow wave activity, with maxima in frontal and central areas. In contrast, affective disorder patients exhibited less slow wave generators mainly in frontal and central regions when compared to healthy subjects and schizophrenia patients. In both samples, frontal ASWA were related to affective symptoms.</p> <p>Conclusion</p> <p>In schizophrenic patients, the regions of ASWA correspond to those identified for gray matter loss. This suggests that ASWA might be evaluated as a measure of altered neuronal network architecture and communication, which may mediate psychopathological signs.</p

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia

Commonalities and differences among vectorized beamformers in electromagnetic source imaging.

A number of beamformers have been introduced to localize neuronal activity using magnetoencephalography (MEG) and electroencephalography (EEG). However, currently available information about the major aspects of existing beamformers is incomplete. In the present study, detailed analyses are performed to study the commonalities and differences among vectorized versions of existing beamformers in both theory and practice. In addition, a novel beamformer based on higher-order covariance analysis is introduced. Theoretical formulas are provided on all major aspects of each beamformer; to examine their performance, computer simulations with different levels of correlation and signal-to-noise ratio are studied. Then, an empirical data set of human MEG median-nerve responses with a large number of neuronal generators is analyzed using the different beamformers. The results show substantial differences among existing MEG/EEG beamformers in their ways of describing the spatial map of neuronal activity. Differences in performance are observed among existing beamformers in terms of their spatial resolution, false-positive background activity, and robustness to highly correlated signals. Superior performance is obtained using our novel beamformer with higher-order covariance analysis in simulated data. Excellent agreement is also found between the results of our beamformer and the known neurophysiology of the median-nerve MEG response

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching' early non-responders to another antipsychotic is a better strategy than ‘staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as ⩾20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2–6 mg/day or switch to olanzapine 10–20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients

Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia

Objective: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia. Method: The patients were randomly assigned to one of the medication groups and received treatment for 8 weeks. Changes in Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, and Clinical Global Impression scores were used as evaluations of treatment efficacy. Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms. Results: Both sertindole and haloperidol were comparably effective in the treatment of psychosis, and all dose levels were significantly more effective than placebo. For the treatment of negative symptoms, only sertindole, 20 mg/day, was significantly more effective than placebo. For all extrapyramidal symptom measures, sertindole was clinically and statistically indistinguishable from placebo, and rates of extrapyramidal symptoms were not dose related. All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole. Adverse events associated with sertindole treatment were mild in severity. Conclusions: Sertindole is a new antipsychotic agent effective for the treatment of both the Positive and negative symptoms of schizophrenia, with motor side effects that are indistinguishable from those associated with placebo