Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson's disease
Introduction
Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by motor dysfunctions such as tremor, rigidity, bradykinesia and impaired postural reflex. In PD, the major pathological changes occur in the nigrostriatal dopaminergic neurons, part of which are innervated to the supplementary motor area (SMA) or primary motor cortex via the putamen, globus pallidus, and thalamus, although numerous non-dopaminergic neurons in other parts of the brain are also impaired [1]. The SMA interacts with the primary motor cortex [2] and modulates volitional motor function. Several lines of evidence suggest impaired SMA function in PD. For example, movement-related potentials derived from the SMA have been found to be decreased in PD [3], [4]. After pallidotomy followed by improved motor performance, movement-related changes of the regional cerebral blood flow (rCBF) have been demonstrated to increase in both the SMA and premotor cortex but not in the primary motor cortex [5]. Thus, for the comprehensive understanding of pathophysiological changes in PD, it is important to elucidate the cortical functions, which are closely related to the nigrostriatal pathways. In some studies, in comparison with controls, regional cerebral metabolism (rCMR) or rCBF in PD patients has been reported to be decreased in the frontal [6], [7], [8], [9], [10], parietal [7], [10], [11], [12], [13], [14], [15], [16], [17], [18], temporal [6], [7], [10], and occipital [7], [10], [16], [18], [19] lobes, as well as in the cerebellum [6], while in others, it has been observed to be unchanged in the occipital lobe [6] and cerebellum [10]. In addition, abnormalities in basal ganglia have been reported [6], [8], [10], [13], [18], [20], [21], although the results were not consistent among these studies. This inconsistency may be due to several causes. First, in most studies, rCBF or rCMR values might be affected not only by motor impairments, but also by aging, cognitive dysfunction, the effects of drugs and so on. Second, selected regions of interest (ROIs), dependent on the observer's a priori choice and hypothesis, were not always consistent with the real distribution of abnormalities and might have been influenced by brain volume and the extent of brain atrophy. The anatomical normalization technique enables us to compare individual brain images on a voxel by voxel basis, even if the size and shape of each image are different [22], [23]. In fact, using statistical parametric mapping (SPM), which is one method of anatomical normalization, increases in rCBF in the putamen, globus pallidus, insula, and inferior temporal gyrus, and so on have been demonstrated in PD [24]. However, rCBF data in the basal ganglia and the each cortical area may be easily affected by artifacts due to cortical or subcortical atrophy not uncommon in PD cases [25]. Because the variations in cortical or subcortical atrophy cannot be compensated for by the anatomical normalization technique alone, in this study, the extent of brain atrophy was evaluated using X-ray CT, and then PD cases without obvious brain atrophy were subjected to the SPM analysis of single-photon emission computed tomographic (SPECT) imaging.
Section snippets
Subjects
All PD cases were diagnosed by a neurologist following the United Kingdom Parkinson's Disease Brain Bank criteria for idiopathic PD [26]. First, the extent of brain atrophy was evaluated in all subjects using X-ray CT. Then, to minimize artifacts, PD cases showing minor ischemic lesions or a brain atrophy score (BAS, see later) less than the mean minus 2SD of controls were excluded from the present analyses. The 18 patients who fulfilled the above criteria were subjected to SPECT analysis, the
Results
The controls minus PD comparison demonstrated a rCBF decrement in the left SMA and the right dorsolateral prefrontal cortex (DLPFC) (uncorrected p<0.001, Fig. 1A and Table 2), and additionally, in the right SMA and the left DLPFC (uncorrected p<0.005, Fig. 1B and Table 2). Compared with the controls, the rCBF decrements in the SMA were evident both in the I/II (uncorrected p<0.05, data not shown) and III/IV (uncorrected p<0.001, Fig. 2A and Table 3) subgroups, but there were no significant
Discussion
In PD, activation studies using positron emission tomography [5], [33], [34] and SPECT [35] imaging have clearly revealed a decreased activation in the SMA, insular cortex, anterior cingulate area, etc. However, previous studies which did not include motor tasks failed to show rCBF decreases in these areas. In this study, first we excluded patients showing brain atrophy and then SPECT images of the study patients were compared with age-matched controls using the SPM technique without motor
Acknowledgments
We are greatly indebted to the staff of the Institute of Development, Aging and Cancer, Tohoku University and, in particular, to Mr. Tachio Sato and Mr. Kazuya Kumekawa for excellent technical assistance.
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