Yasuhiro Nagahama

Brain functional activity during gait in normal subjects : a SPECT study

The purpose of this study was to evaluate changes in brain activity during voluntary walking in normal subjects using technetium-99m-hexamethyl-propyleneamine oxime single photon emission computed tomography. This study included 14 normal subjects. Statistical parametric mapping analysis revealed that the supplementary motor area, medial primary sensorimotor area, the striatum, the cerebellar vermis and the visual cortex were activated. These results suggested that the cerebral cortices controlling motor functions, visual cortex, basal ganglia and the cerebellum might be involved in the bipedal locomotor activities in humans.

Evidence of misery perfusion and risk for recurrent stroke in major cerebral arterial occlusive diseases from PET.

OBJECTIVES--In major cerebral arterial occlusive diseases, patients with inadequate blood supply relative to metabolic demand (misery perfusion) may be at increased risk for cerebral ischaemia. This study investigated whether patients showing misery perfusion on PET have a high risk of recurrent ischaemic stroke. METHODS--The relation between the regional haemodynamic status of cerebral circulation and the subsequent risk of recurrent stroke was prospectively evaluated in 40 patients with symptomatic internal carotid or middle cerebral arterial occlusive diseases who underwent PET. Patients were divided into two haemodynamic categories according to the mean hemispheric value of oxygen extraction fraction in the hemisphere supplied by the artery with symptomatic disease: patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction (misery perfusion). All patients were followed up for at least 12 months. RESULTS--The one year incidence of ipsilateral ischaemic strokes for patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction were two of 33 and four of seven patients respectively. A significantly higher incidence of ipsilateral strokes was found in patients with increased oxygen extraction fraction (Fishers exact test; P = 0.005). In patients with increased oxygen extraction fraction, three of four strokes were watershed infarctions and the location of the infarction corresponded with the area of increased oxygen extraction fraction. CONCLUSION--These findings contradict conclusions of a previous study and suggest that patients with major cerebral arterial occlusive diseases and misery perfusion have a high risk for recurrent ischaemic stroke.

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease

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 Alzheimers 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 different 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, middle-anterior, 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 different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.

Cortical processing mechanism for vocalization with auditory verbal feedback.

To investigate the relationship between motor and sensory speech center, cortical activity was examined using PET while normal subjects perceived their own voice which sounded different to the articulated one. The results showed significant activation in the superior temporal gyri with absence of activity in the supplementary motor area (SMA). In a previous study we found significant activation in SMA with no activity in the superior temporal gyrus when normal subjects simply vocalized. Thus, two different cortical pathways for vocalization were delineated: programmed pathway in SMA, and pathway with auditory verbal feedback. The former is thought to be the mature system in the adult, and the latter may be related to speech acquisition.

Neural correlates of psychotic symptoms in dementia with Lewy bodies

The aim of this study was to investigate the association between psychotic symptoms in dementia with Lewy bodies and brain perfusion on single photon emission tomography. Based on factor analysis in 145 patients, psychotic symptoms were classified into five symptom domains (factor 1 to 4-related symptoms and delusions). The relationship between each symptom domain and brain perfusion was assessed in 100 patients with dementia with Lewy bodies, while accounting for the effects of age, sex, dementia severity, parkinsonism and dysphoria. Factor 1 symptoms (Capgras syndrome, phantom boarder, reduplication of person and place and misidentification of person) represented misidentifications, and were significantly related to hypoperfusion in the left hippocampus, insula, ventral striatum and bilateral inferior frontal gyri. Factor 3 symptoms (visual hallucination of person and feeling of presence) represented hallucinations of person and were related to hypoperfusion in the left ventral occipital gyrus and bilateral parietal areas. Delusions of theft and persecution were associated with relative hyperperfusion in the right rostral medial frontal cortex, left medial superior frontal gyrus and bilateral dorsolateral frontal cortices. This study revealed that different psychotic symptoms in dementia with Lewy bodies were associated with distinguishable cerebral networks. Visual hallucinations were related to dysfunction of the parietal and occipital association cortices, misidentifications were related to dysfunction of the limbic-paralimbic structures and delusions were related to dysfunction of the frontal cortices. Our findings provide important insights into the pathophysiological mechanisms underlying psychotic symptoms in dementia with Lewy bodies.

Age-related changes in cerebral blood flow activation during a Card Sorting Test

Abstract To determine the age-related changes in the neural processing involved in the Modified Card Sorting Test (MCST), we measured cerebral blood flow (CBF) during performance of the MCST and of the number-matching task in young and elderly subjects using positron emission tomography. Compared with that during the number-matching task, CBF during the MCST was increased in the left dorsolateral prefrontal cortex (DLPFC), left inferior parietal lobule, and left striate and prestriate cortices in both age groups. However, CBF activation in these areas was significantly lower in the elderly subjects than the young subjects. Furthermore, CBF activation was reduced in the left DLPFC, right parahippocampal gyrus, and prestriate cortex in proportion to the increase in the number of perseverative errors with aging. These results suggest that the impaired MCST performance in elderly subjects may be due, in part, to dysfunction of the network involving certain cortical areas such as the prefrontal and parahippocampal cortices, although the essential neural circuits for MCST performance were still preserved even in the elderly subjects.

Neural activity during attention shifts between object features

TO investigate the neural mechanisms involved in shifting attention we used positron emission tomography to examine regional cerebral blood flow (rCBF) during a task that demands shifting attention between color and shape. Significant activation was observed in the right dorsal prefrontal cortex and parieto-occipital cortex at all frequencies of attention shifts. The frequency of shifts between categories correlated significantly with rCBF in the rostral part of the supplementary motor area and the left precuneus, whereas the number of successive correct responses correlated with rCBF in the orbitofrontal cortex and the caudate nucleus. This study suggests that several prefrontal regions may participate in the processes of shifting attention in different ways.

Neural control of micturition in man examined with single photon emission computed tomography using 99mTc-HMPAO.

THE neural mechanisms of micturition in man were studied using single photon emission computed tomography (SPECT). The areas activated during micturition, relative to the resting state, were the upper pons, the left sensorimotor cortex, the right frontal cortex and the bilateral supplementary motor areas. Some of these regions have been established by clinical and experimental studies as the neural control centre for voiding. We confirmed the neural micturition centre in healthy men using SPECT for the first time.

The cerebral correlates of different types of perseveration in the Wisconsin Card Sorting Test

Objectives: To explore the neural substrates corresponding to the perseverative errors in the Wisconsin Card Sorting Test (WCST). Methods: The study examined the correlations between the WCST performances and the SPECT measurements of regional cerebral blood flow (rCBF) in subjects with neurodegenerative dementia. Negative non-linear correlations between the rCBF and the two different types of the perseverative errors (“stuck-in-set” and “recurrent” perseverative errors) were calculated on a voxel basis and volume-of-interest basis in the mixed groups of 72 elderly and dementia patients. Results: The stuck-in-set perseverative error was associated with the reduced rCBF in the rostrodorsal prefrontal cortex, whereas the recurrent perseverative error was related to the left parietal activity but not to the prefrontal activity. Conclusions: These findings augment evidence that the rostrodorsal prefrontal cortex crucially mediates attentional set shifting, and suggest that the stuck-in-set perseverative errors would be a true pathognomonic sign of frontal dysfunction. Moreover, this study shows that the recurrent perseverative errors may not be associated closely with the prefrontal function, suggesting that this error and the stuck-in-set error should be differentially estimated in the WCST.

Cerebral Correlates of the Progression Rate of the Cognitive Decline in Probable Alzheimer’s Disease

Objective: To evaluate the possible relation between the rate of cognitive deterioration in patients with probable Alzheimer’s disease (AD) and the distribution pattern of neural dysfunction. Methods: The regional cerebral blood flow (rCBF) was measured in rapidly and slowly progressing groups of AD patients using single-photon emission computed tomography and was compared between the groups. While controlling for demographic and clinical factors that could be associated with the stage and prognosis of the illness, the deterioration rate of the Mini Mental State Examination (MMSE) score was significantly greater in the rapidly progressing group than that in the slowly progressing group. Results: The rCBF in the right posterodorsal, anterior and superior prefrontal cortices and the inferior parietal cortex was significantly lower in the rapidly progressing patients. Moreover, lower perfusion in these regions correlated significantly with rapid deterioration in the MMSE. Conclusions: These findings suggest that the rCBF values in these cortical regions could be useful in predicting which AD patients will show a relatively rapid cognitive decline.