Single photon emission computed tomography was used to evaluate regional cerebral blood flow changes during gait on a treadmill in 10 patients with Parkinson's disease and 10 age-matched controls. The subjects were injected with [99mTc]hexamethyl-propyleneamine oxime twice: while walking on the treadmill, which moved at a steady speed, and while lying on a bed with their eyes open. On the treadmill, all subjects walked at the same speed with their preferred stride length. The patients showed typical hypokinetic gait with higher cadence and smaller stride length than the controls. In the controls, a gait-induced increase in brain activity was observed in the medial and lateral premotor areas, primary sensorimotor areas, anterior cingulate contex, superior parietal cortex, visual cortex, dorsal brainstem, basal ganglia and cerebellum. The Parkinson's disease patients revealed relative underactivation in the left medial frontal area, right precuneus and left cerebellar hemisphere, whereas they showed relative overactivity in the left temporal cortex, right insula, left cingulate cortex and cerebellar vermis. This is the first experimental study showing that the dorsal brainstem, which corresponds to the brainstem locomotor region in experimental animals, is active during human bipedal gait. The reduced brain activity in the medial frontal motor areas is a basic abnormality in motor performance in Parkinson's disease. The underactivity in the left cerebellar hemisphere, in contrast to the overactivity in the vermis, could be associated with a loss of lateral gravity shift in parkinsonian gait.
Neuropsychological tests that require shifting an attentional set, such as the Wisconsin Card Sorting Test, are sensitive to frontal lobe damage. Although little information is available for humans, an animal experiment suggested that different regions of the prefrontal cortex may contribute to set shifting behavior at different levels of processing. Behavioral studies also suggest that set shifting trials are more time consuming than non-set shifting trials (i.e. switch cost) and that this may be underpinned by differences at the neural level. We determined whether there were differential neural responses associated with two different levels of shifting behavior, that of reversal of stimulus-response associations within a perceptual dimension or that of shifting an attentional set between different perceptual dimensions. Neural activity in the antero-dorsal prefrontal cortex increased only in attentional set shifting, in which switch costs were significant. Activity in the postero-ventral prefrontal cortex increased not only in set shifting but also in reversing stimulus-response associations, in which switch costs were absent. We conclude that these distinct regions in the human prefrontal cortex provide different levels of attention control in response selection. Thus, the antero-dorsal prefrontal cortex may be critical for higher order control of attention, i.e. attentional set shifting, whereas the postero-ventral area may be related to a lower level of shift, i.e. reorganizing stimulus-response associations.
Parkinson's disease (PD) patients often show marked improvement of hypokinetic gait when exposed to special stimuli. To investigate physiological mechanisms underlying this “paradoxical gait” induced by visual cues in PD patients, we examined regional cerebral blood flow changes during gait on a treadmill guided by two different visual cues, the lines oriented transversely to the direction of walk (TL) and the lines parallel to it (PL). Ten PD patients and 10 age‐matched controls received injections of 99mTc‐hexamethylpropyleneamine oxime twice, once during each walking condition. Brain perfusion images were obtained by single‐photon emission computed tomography. When affected by TL, PD patients showed marked improvement of gait parameters, mainly reduction of cadence. In regional cerebral blood flow analysis, when TL was compared with PL, both groups had common activation in the posterior parietal cortex and cerebellar hemispheres. Especially in the right lateral premotor cortex, PD patients showed enhanced activation induced by TL to a significantly greater degree than the controls. The present study indicates that the network dedicated to visuomotor control, particularly the lateral premotor cortex, plays an important role in the development of the paradoxical gait induced by special visual stimuli in PD patients. Ann Neurol 1999;45:329–336
Objectives-The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was diVerent among patients with FTD, PSP, or early onset AD. Methods-Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middleanterior, middle-posterior, and posterior portions. Results-Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. Conclusion-Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are diVerent among patients with FTD, PSP, or early onset AD. DiVerential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia. (J Neurol Neurosurg Psychiatry 2000;69:623-629)
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