Thalamic gray matter changes in unilateral Parkinsonian resting tremor: a voxel-based morphometric analysis of 3-dimensional magnetic resonance imaging Jan Kassubek a , Freimut D. Juengling b , Bernhard Hellwig a, * , Joachim Spreer c , Carl H. Lu ¨ cking a a Department of Neurology, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany b Division of Nuclear Medicine, Department of Radiology, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany c Section of Neuroradiology, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany Received 7 August 2001; received in revised form 14 January 2002; accepted 16 January 2002 Abstract The thalamus is assumed to be involved in the generation of Parkinsonian tremor. Ten patients with tremor-dominant idiopathic Parkinson’s disease (IPD) and strictly unilateral resting tremor were investigated by cerebral high-resolution 3- dimensional magnetic resonance imaging (MRI). MRI data were analyzed by an observer-independent morphometric technique, voxel-based morphometry (VBM). For VBM, MRI data were automatically normalized and segmented, then gray matter volumes were analyzed on a voxel-by-voxel basis in comparison to an age-matched control group using Statistical Parametric Mapping (SPM99). Highly significant structural changes, i.e. locally increased gray matter concen- trations (P , 0:001), were found in the nucleus ventralis intermedius (VIM) of the thalamus contralateral to the tremor side and were significantly covariant with tremor amplitudes. On the one hand, these changes were localized in close vicinity to a thalamic focal hypermetabolism as revealed by a previous positron emission tomography study in unilateral Parkinsonian tremor patients. On the other hand, the localization of the focal structural changes in VIM corresponds with the generally accepted target area of tremor surgery in IPD. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Parkinson’s disease; Magnetic resonance imaging; Statistical parametric mapping; Thalamus; Tremor; Voxel-based morpho- metry Resting tremor in idiopathic Parkinson’s disease (IPD) is generally assumed to be generated by a central oscillatory neuronal network. Functional brain imaging especially with positron emission tomography (PET) has provided novel insights into the pathophysiology of Parkinsonian tremor (for review see Ref. [3]). The important role of thalamic nuclei within the tremor-associated network was demon- strated. These imaging findings were in line with the evidence by clinical and neurophysiological studies [9,14]. In a recent PET study in IPD patients with unilateral tremor, we showed a regional hypermetabolism in the thalamus which covaried with tremor amplitudes and was located contralateral to the tremor side [7]. These focal metabolic changes were localized in a thalamic subnucleus called ventral lateral anterior nucleus (VLa) which is known from anatomical studies to be connected to the basal ganglia [10]. Hence, the region of the focal hypermetabolism was localized slightly anterior to the target nucleus for stereo- tactic tremor surgery which receives cerebellar input and is referred to as nucleus ventralis intermedius (VIM, according to the Hassler terminology) [14]. The question remained open if the functional changes revealed by PET were asso- ciated with focal structural changes in the thalamus (which are accessible by volumetric measurements using magnetic resonance imaging (MRI)). In a previous investigation using MRI-based volumetry by Schulz et al. [13], striatal, cere- bellar and brainstem volumes were reported to be normal in IPD patients. In contrast, Alegret et al. described focal degeneration in the basal ganglia and substantia nigra and diffuse cerebral atrophy in IPD patients with cognitive defi- cits [1]. In none of these studies structural changes in the thalamus were reported. In this study, the brains of patients with unilateral tremor as the dominant feature of IPD were studied by volumetric Neuroscience Letters 323 (2002) 29–32 0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(02)00111-8 www.elsevier.com/locate/neulet * Corresponding author. Tel.: 149-761-2705001; fax: 149-761- 2705310. E-mail address: hellwigb@nz.ukl.uni-freiburg.de (B. Hellwig).