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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Univ.-Prof. Dr. D. F. Braus
Universitätsklinik für Psychiatrie
Martinistr. 52
20246 Hamburg
Email: dfbraus@zi-mannheim.de
