Funktionelle Kernspintomographie (fMRI) und Psychopharmakaeffekte: Eine Standortbestimmung

Zusammenfassung

Die funktionelle Magnetresonanztomographie (fMRI) ist inzwischen ein etabliertes Verfahren zur nicht invasiven Untersuchung des lebenden Gehirns. Mit ihrer hohen zeitlichen und räumlichen Auflösung erlaubt die Methode die Erstellung funktioneller Aktivitätslandkarten während perzeptueller, kognitiver und emotionaler Leistungen.

In jüngster Zeit wird die fMRI auch zunehmend zur Analyse von regional spezifischen Veränderungen der Hirnaktivität durch psychoaktive Substanzen wie Nikotin, Kokain, Lorazepam, Scopolamin, Antipsychotika oder Antidepressiva eingesetzt. Tierexperimentelle Studien widmen sich dabei der Untersuchung von Psychopharmakaeffekten auf die MR-Signalveränderungen in verschiedenen Hirnarealen bei vergleichsweise hohen Magnetfeldstärken (> 4 Tesla). Dagegen konzentrieren sich fMRI-Studien an Probanden und psychiatrischen Patienten auf die zerebrale Aktivität nach einmaliger Substanzapplikation (single challenge) sowie adaptive Effekte des ZNS durch längerfristige psychotrope Medikation. Die Ergebnisse erlauben Rückschlüsse auf hirnphysiologische und neuropharmakologische Prozesse, die beispielsweise im Rahmen präklinischer Wirksamkeitsstudien, Responderanalysen und der Erforschung pathogenetischer Fragestellungen psychiatrischer Erkrankungen relevant sind.

Neben den Möglichkeiten, die dieses neue Verfahren bietet, ist seine Nutzung mit vielfältigen methodischen Anforderungen und Einschränkungen verknüpft. Dazu gehört die Kontrolle von Bewegungsartefakten und interferierenden psychologischen Variablen sowie die exakte Spezifikation des experimentellen Designs, standardisierte Analysen zur Datennachbearbeitung und die Berücksichtigung technischer Einschränkungen. Dieser Artikel gibt einen Überblick über das zugrunde gelegte Modell der Hirnfunktion, derzeitige Anwendungen, zukünftige Möglichkeiten und methodische Grenzen der fMRI in der Erforschung pharmakologischer Fragestellungen.

Abstract

Functional magnetic resonance imaging (fMRI) is well established for the examination of functional activity in the living brain. The method permits the development of functional activation maps during perceptual, cognitive and emotional efforts with a high temporal and spatial resolution.

As of late there has been growing interest in using this technique to investigate regionally specific brain activity following the administration of drugs such as nicotine, cocaine, lorazepam, scopolamine, antipsychotics or antidepressants. Studies in experimental animals investigate signal changes associated with the administration of psychopharmacological substances in different brain areas using a high magnetising field (> 4 Tesla). FMRI-studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects of the CNS due to long- term medication. Their results provide insights into brain physiology and neuropharmacological mechanisms which are in turn relevant for preclinical pharmacological studies, responder analyses and for the investigation of pathogenetic models in psychiatric diseases.

However, with these new opportunities, additional methodological considerations and limitations emerge. Besides the need of controlling motion artefacts, the influence of interfering psychological variables, an exact specification of the experimental design, a standardised analysis for data adjustment and technical limitations have to be considered. This article provides an overview of the underlying model of brain function, present applications, future possibilities and methodological limitations of fMRI for the understanding of human psychopharmacology.

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