SPINDLESINSCHIZO

A study of the spontaneous and evoked spindle activity in schizophrenic and control subjects

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 Obiettivo del progetto (Objective)

'Understanding the pathophysiology of schizophrenia is one of the most compelling challenges facing current psychiatric research. Several electrophysiological and neuroimaging studies have explored the brain activity of schizophrenics and controls while these subjects performed various cognitive tasks to identify brain abnormalities specific for schizophrenia. In this study, schizophrenics and controls will be investigated while asleep. Sleep EEG recordings minimize possible waking-related confounding factors, including level of attention and presence of psychotic symptoms, and offer the opportunity to study sleep-specific rhythms such as sleep spindles. In a recent study with a 256 channel high density EEG (hd-EEG), Ferrarelli et al. (AJP 2007) revealed that schizophrenics (n=18) had a significant reduction in several spindle parameters in a centroparietal area compared to controls (n=17) during the first sleep episode. Other recent studies by Massimini et al. have demonstrated the feasibility of combining TMS with hd-EEG to investigate changes of effective connectivity in healthy subjects between waking and sleep (Science 2005, PNAS in press). In this study, hd-EEG recordings will be performed in schizophrenics and controls with two aims: 1) studying spontaneous brain activity, particularly spindles, during sleep 2) exploring the dynamics of evoked responses during sleep, especially the modulation of spindle activity following an evoked potential. Hd-EEG will be used to assess the stability of the spindle pattern over time and to investigate larger groups, including patients without schizophrenia taking antipsychotics. Evoked activity during sleep will be explored using both auditory tones and TMS to induce slow oscillations or K-complexes, which are often followed by spindles. It is expected that a comprehensive investigation of spontaneous and evoked spindle activity will provide a parameter which minimizes the overlap between schizophrenics and controls.'

Introduzione (Teaser)

European researchers are using electrophysiological and neuroimaging techniques to characterise brain activity in the sleeping schizophrenic brain.

Descrizione progetto (Article)

Sleep spindles are bursts of brain activity that herald the passage of stage 1 sleep into the deeper sleep, stage 2. Spindle activity reflects some potentially important brain activity and researchers are delving into the brain's electrical patterns at night to detect dysfunctions. Looking at the sleeping brain minimises activities such as psychotic symptoms and impaired cognitive ability that complicate brain electroencephalography (EEG) patterns when awake.

A team of scientists under the umbrella of the Spindlesinschizo project are researching the possibility of so-called sleep spindles as a biomarker for brain abnormalities in schizophrenia. Recent studies have identified that schizophrenics show a significant reduction in spindle parameters when compared with controls.

Spindlesinschizo researchers are studying schizophrenic patients, patients on anti-psychotic therapy and controls. Their aims are to study EEG patterns, particularly slow waves and sleep spindles, as well as characterise sleep EEG activity including the oscillations of slow waves (1Hz) and so-called K complexes (large waves).

A total of over 110 individuals were subjected to all-night high-density EEG recordings. Schizophrenics showed deficits in spindle number and integrated spindle activity (ISA) in prefrontal, centroparietal and temporal regions of the brain. By contrast, there was no evidence of slow wave impairments.

Spindlesinschizo data has important implications. First of all, the spindle deficits can be attributed to dysfunction of neural circuits as they do not occur in non-schizophrenics on anti-psychotics. The next important conclusion is that the defective circuits may lie in the thalamus as cells in this region are involved in the sleep spindle phenomenon. Finally, it follows that sleep spindles may indeed be used as a reliable marker for schizophrenia.

Project scientists are going to further explore the use of the sleep spindle deficit as a viable marker. The scientists are investigating if a low-density EEG montage can be used to establish the presence of sleep spindles. If so, whole night recordings can be taken from patients in non-research settings such as hospitals and clinics.

Another research angle is to characterise the start of sleep spindles particularly in view of the fact that they are preceded by slow waves. Sleep spindles may therefore in the future be 'induced' in patients with schizophrenia.

The Spindlesinschizo project has created the basis for an understanding of the pathophysiology of schizophrenia, one of the most prominent challenges in psychiatry today. Identification of brain abnormalities will open the door to new improved therapies. Extension of the knowledge may be applicable to the role of sleep in learning and development.