A framework for targeting alternative brain regions with repetitive transcranial magnetic stimulation in the treatment of depression

A framework for targeting alternative brain regions with repetitive transcranial magnetic stimulation in the treatment of depression

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J Psychiatry Neurosci 2005;30(2):91-97

Dennis J.L.G. Schutter, PhD; Jack van Honk, PhD

Affective Neuroscience Section, Helmholtz Research Institute, Utrecht University, Utrecht, The Netherlands.

Abstract

It has been argued that clinical depression is accompanied by reductions in cortical excitability of the left prefrontal cortex (PFC). In support of this, repetitive transcranial magnetic stimulation (rTMS), which is a method of enhancing cortical excitability, has shown antidepressant efficacy when applied over the left PFC, although the overall therapeutic effects remain inconclusive. The cerebral pathophysiology of depression is, however, not limited to dysfunctions in the PFC, thus, targeting alternative brain regions with rTMS may provide new therapeutic windows in the treatment of depression. Evidence from electroencephalography and lesion studies suggests that not only is the left PFC involved in depression but also the parietal cortex and cerebellum. Furthermore, rTMS over the parietal cortex and the cerebellum has been found to improve mood and emotional functioning, at least in healthy volunteers. We have integrated these findings in an rTMSoriented theoretical framework for the neurobiology of low mood and depression. To establish the possible therapeutic efficacy of this model, whereby, for example, the application of slow rTMS over the right parietal cortex and fast rTMS over the cerebellum may be beneficial in different subtypes of depression, clinical rTMS studies that target the parietal cortex and cerebellum are warranted.

Résumé

On a soutenu que des réductions de l’excitabilité corticale du cortex préfrontal gauche (CPF) accompagnent la dépression clinique. À l’appui de cette affirmation, on a montré l’effet antidépresseur efficace de la magnétostimulation transcrânienne répétitive (MSTr), moyen d’améliorer l’excitabilité corticale, appliquée au CPF gauche, même si les effets thérapeutiques globaux demeurent non concluants. La pathophysiologie cérébrale de la dépression n’est toutefois pas limitée aux dysfonctions du CPF et c’est pourquoi l’application de la MSTr à d’autres régions du cerveau pourrait offrir de nouveaux moyens de traiter la dépression. Les données électroencéphalographiques et tirées d’études de lésions indiquent que non seulement le CPF gauche intervient dans la dépression, mais aussi le cortex pariétal et le cervelet. De plus, la MSTr appliquée au cortex pariétal et au cervelet améliore la thymie et l’adaptation affective, du moins chez des volontaires en bonne santé. Nous avons intégré ces constatations dans un cadre théorique axé sur la MSTr pour la neurobiologie de l’hypothymie et de la dépression. Pour déterminer l’efficacité thérapeutique possible du modèle lorsque, par exemple, l’application d’une MSTr lente au cortex pariétal droit et d’une MSTr rapide au cervelet peut se révéler bénéfique dans différents sous-types de dépression, des études cliniques sur la MSTr appliquée au cortex pariétal et au cervelet sont justifiées.


Medical subject headings: cerebellum; depression; mood; parietal cortex; prefrontal cortex; transcranial magnetic stimulation.

Submitted Aug. 31, 2003; Revised Feb. 6, 2004; Accepted Mar. 17, 2004

Acknowledgements: Dr. Schutter was supported by an Innovational Research Grant (#451-04-070) and Dr. van Honk was supported by an Innovational Research Grant (# 016-005-060) from the Netherlands Organization for Scientific Research (NWO).

Competing interests: None declared.

Contributors: The study was conceived by Drs. Kolla and Wei, and all authors participated in the experimental design. Drs. Kolla and Wei were responsible for data acquisition. All authors participated in data interpretation and drafting the article, and gave final approval for the version to be published.

Correspondence to: Dr. Dennis J.L.G. Schutter, Affective Neuroscience Section, Department of Psychonomics, Helmholtz Research Institute, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands; fax 31 30 2534511; d.schutter@fss.uu.nl