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Cerebral Cortex Advance Access published online on October 10, 2007
Cerebral Cortex, doi:10.1093/cercor/bhm167
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© 2007 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anatomical Connectivity of the Subgenual Cingulate Region Targeted with Deep Brain Stimulation for Treatment-Resistant Depression

H. Johansen-Berg1, D. A. Gutman2, T. E. J. Behrens1,3, P. M. Matthews1,4,5, M. F. S. Rushworth1,3, E. Katz2, A. M. Lozano6 and H. S. Mayberg2

1 Centre for Functional MRI of the Brain, University of Oxford, Oxford OX3 9DU, UK, 2 Emory University School of Medicine, Atlanta, GA 30322, USA, 3 Deparment of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK, 4 Clinical Imaging Centre, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Hammersmith Hospital, London W12 0NN, UK, 5 Deparment of Clinical Neurosciences, Imperial College, London W6 8RF, UK, 6 Toronto Western Hospital, Division of Neurosurgery, Toronto, Ontario M5T 2S8, Canada

Address correspondence to Dr Heidi Johansen-Berg, Oxford Centre for Functional MRI of the Brain, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 0HS, UK. Email: heidi{at}fmrib.ox.ac.uk.

Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.

Key Words: anterior cingulate • deep brain stimulation • depression • diffusion tractography • human • MRI


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