1. ¹INSERM, U797 Research Unit 'Neuroimaging and Psychiatry', IFR49, Orsay, France
2. ²CEA, 'Neuroimaging and Psychiatry' U797 Unit, Hospital Department Frédéric Joliot & Neurospin, I2BM, Orsay, France
3. ³Université Paris-Sud, UMR U797, Orsay and Université Paris 5 Rene Descartes, UMR U797, Paris, France
4. ⁴APHP, Department of Psychiatry and Addictology, Paul Brousse Hospital, Villejuif, France
5. ⁵APHP, Addiction Treatment Center, Emile Roux Hospital, Limeil-Brevannes, France
6. ⁶Image Analysis and Structural Anatomy Group, Neurospin, IFR 49, CEA, Gif-sur-Yvette, France

Correspondence: Dr J-L Martinot, CEA-INSERM U797, Hospital Department Frédéric Joliot, I2BM, SHFJ-CEA. 4, place du Général Leclerc, 91401 Orsay. France. Tel: +33 1 6986 7757; Fax: +33 1 6986 7810; E-mail: jean-luc.martinot@cea.fr

Received 16 November 2007; Revised 23 May 2008; Accepted 23 May 2008; Published online 9 July 2008.

Abstract

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n=20) and a group of healthy men (n=24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.