Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's disease is restricted to the rostral part of the SMA and to the dorsolateral prefrontal cortex. These results also show that, apart from the lateral premotor and parietal cortices, increased fMRI signals can be found in other cortical motor areas of these patients, including the posterior SMA, the anterior cingulate cortex and the primary sensorimotor cortices, which are then likely to participate in the same putative attempt by the dopamine-denervated brain to recruit parallel motor circuits in order to overcome the functional deficit of the striatocortical motor loops.

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson’s disease and 22 control subjects underwent 3-T magnetic resonance imaging with T₂*-weighted, whole-brain T₁-weighted and diffusion tensor imaging scans. The mean R₂* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson’s disease and control subjects. Comparisons were also performed using voxel-based analysis of R₂*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson’s disease displayed significantly higher R₂* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson’s disease from controls. The markers comprising discriminating combinations were R₂* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson’s physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R₂*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson’s disease and, possibly, of other subcortical pathologies.

Human awareness of left space may be disrupted by cerebral lesions to the right hemisphere (hemispatial neglect). Current knowledge on the anatomical bases of this complex syndrome is based on the results of group studies that investigated primarily the best known aspect of the syndrome, which is visual neglect for near extrapersonal (or peripersonal) space. However, another component–neglect for personal space–is more often associated with, than double-dissociated from, extrapersonal neglect, especially, in chronic patients. The present investigation aimed at exploring the anatomical substrate of both extrapersonal and personal neglect by using different advanced methodological approaches to lesion–function correlation. Fifty-two right ischaemic patients were submitted to neuropsychological assessment and in-depth MRI evaluation. The borders of each patient's lesion were delimited onto its own high-resolution anatomical image and then submitted to an automated spatial normalization algorithm. Besides conventional lesion density plots and subtraction analysis, region-based statistical analyses were performed on percentage values of the lesioned tissue also using a new parcellation of the white matter (WM). Data were finally submitted to voxelwise statistical analysis using a recently proposed method (voxel-based lesion–symptom mapping). Results converged in showing that awareness of extrapersonal space is based on the integrity of a circuit of right frontal (ventral premotor cortex and middle frontal gyrus) and superior temporal regions, whereas awareness of personal space is rooted in right inferior parietal regions (supramarginal gyrus, post-central gyrus and especially the WM medial to them). Common but less crucial regions for both neglect sub-types were located in the temporo-peri-Sylvian cortex. We suggest that extrapersonal space awareness critically involves a ventral circuit recently described for the exogenous allocation and reorienting of attention in space. Disruption of personal space awareness, instead, seems to be due to a functional disconnection between regions important for coding proprioceptive and somatosensory inputs, and regions coding more abstract egocentric representations of the body in space. In conclusion, present data strongly support a segregation of personal and extrapersonal spatial awareness in humans, both from a functional and an anatomical point of view.

• We have measured with single-photon emission tomography the regional cerebral blood flow changes that occurred in the supplementary motor areas and in the primary sensory motor areas during sequential finger-to-thumb opposition movements of the right hand in seven akinetic patients with Parkinson's disease and in nine normal volunteers. Parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine hydrochloride which was able to switch them "on" (on condition). In normal volunteers and parkinsonian patients in the on condition, regional cerebral blood flow significantly increased in the supplementary motor areas and in the contralateral primary sensory motor cortex but not in the ipsilateral primary sensory motor cortex. On the contrary, no significant regional cerebral blood flow change was observed in these areas in parkinsonian patients in the off condition. These results support the hypothesis that a functional cortical motor area deafferentation is involved in the pathophysiological makeup of akinesia and that this abnormality is reversed by dopaminergic drugs.

We compared the rCBF changes induced by the execution of a finger-to-thumb opposition motor task in the cerebellar hemispheres of 12 normal subjects, 12 parkinsonian patients whose medication had been withheld for at least 18 h and 16 parkinsonian patients on medication using single photon emission tomography and i.v. 133Xe. The normal subjects and parkinsonian patients on medication exhibited the same pattern of response, with a significant increase in rCBF in the contralateral primary motor cortex and in the supplementary motor areas. No significant rCBF change was detected in the cerebellum of these two groups; this finding was expected since our technique cannot detect cerebellar activation when the motor task is executed at a relatively low rate and small amplitude as it was in this study. The parkinsonian patients off medication exhibited a markedly different pattern of activation characterized by a significant overactivation in the ipsilateral cerebellar hemisphere and a significant underactivation in the supplementary motor areas. These results suggest that parkinsonian patients off medication may try to compensate for their basal ganglia-cortical loop's dysfunction using other motor pathways involving cerebellar relays.