Decreases in regional cerebral blood flow with normal aging

Positron emission tomographic (PET) images of regional cerebral blood flow (rCBF) from 30 normal, resting volunteers aged 30 to 85 years were analysed to identify areas where rCBF fell with age. Images were anatomically normalised, and a pixel-by-pixel linear regression was performed to remove differences in global CBF between subjects. Pixels at which rCBF then showed a significant (p less than 0.01) negative correlation with age were identified. They were displayed as a statistical parametric map (SPM) of correlations. We demonstrate an age-related decrease in adjusted rCBF in the cingulate, parahippocampal, superior temporal, medial frontal, and posterior parietal cortices bilaterally, and in the left insular and left posterior prefrontal cortices (omnibus significance, chi 2 = 2,291, p less than 0.0001, df = 1). Decreases in rCBF suggest a regionally specific loss of cerebral function with age. The affected areas were all limbic, or association, cortices. Therefore, these decreases may constitute the cerebral substrate of the cognitive changes that occur during normal aging.     

Age and regional cerebral blood flow in schizophrenia: age effects in anterior cingulate, frontal, and parietal cortex

Positron emission tomography ([(15)O] water PET) was used to examine the relationship between age and regional cerebral blood flow (rCBF) in schizophrenia. Forty-nine unmedicated male patients, ages 20-51, underwent imaging during an eyes-closed resting condition. Negative correlations were observed between age and rCBF in the anterior cingulate, as well as in frontal (Brodmann area 8) and parietal cortex (area 40) bilaterally. The observation of reduced rCBF in the anterior cingulate with increased age is consistent with previous findings in healthy subjects. In contrast, the reduced flow observed in the frontal and parietal regions may be unique to schizophrenia.     

Specificity of changes in cerebral blood flow in patients with frontal lobe dementia.

Eight patients with a clinical diagnosis of probable Alzheimer's disease, eight patients with the clinical diagnosis of frontal lobe dementia, and eight controls were examined with single photon emission tomography (SPECT) using 99Tc-HMPAO. Patients with Alzheimer's disease and those with frontal lobe dementia met DSM-III-R criteria for mild dementia and were in the early stages of the illness. Compared with patients with Alzheimer's disease, the group with frontal lobe dementia had significantly lower blood flow in the frontal lobes (dorsolateral and orbital), the anterior temporal cortex, and the basal ganglia. Within the frontal lobe dementia group, blood flow was significantly lower in the orbital than in the dorsal frontal cortex, and in the anterior temporal than in the dorsal temporal cortex. The present study shows the specificity of changes in regional cerebral blood flow in the diagnosis of different types of dementia, and supports the importance of orbitofrontal, anterior temporal, and basal ganglia dysfunction in the production of the psychiatric syndrome of frontal lobe dementia.     

Cerebral blood flow and cerebral oxygen metabolism in patients with dementia of frontal lobe type

This study was designed to investigate the differences in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) between patients with dementia of frontal lobe type and patients with Alzheimer's disease. Positron emission tomography (PET) using 15O steady state inhalation technique was carried out in 5 patients with a clinical diagnosis of dementia of frontal lobe type and 7 patients with a clinical diagnosis of Alzheimer's disease. CBF and CMRO2 were significantly decreased in the frontal cortex except for precentral region in patients with dementia of frontal lobe type in comparison to those values in patients with Alzheimer's disease. However, in patients with dementia of frontal lobe type CBF and CMRO2 in the parietal cortex and the occipital cortex were relatively preserved when compared with patients with Alzheimer's disease. In comparison with values for CBF and CMRO2 in the posterior part of brain [frontal or temporal/(parietal + occipital)/2 ratio], both values in the frontal cortex were markedly decreased in all 5 patients with dementia of frontal lobe type, but there was no marked reduction in the frontal cortex in patients with Alzheimer's disease. In addition, in 2 patients with dementia of frontal lobe type whose duration of the disease was more than 7 years, CBF and CMRO2 in the temporal cortex were markedly reduced in comparison with values in the posterior part of brain. These results suggested that PET findings of marked reduction in CBF and CMRO2 in the frontal cortex are useful to distinguish dementia of frontal lobe type from Alzheimer's disease.     

Diminished regional cerebral blood flow during the intercritical period in temporal lobe epilepsy

Hemisphere and regional cerebral blood flow (CBF) were determined during interictal periods by intravenous Xenon 133 in 43 patients considered to have "temporal" epilepsy and presenting complex partial attacks with altered consciousness and lateralized EEG anomalies predominant in the temporal region. Brain scans were normal in all cases. Three subgroups were differentiated according to EEG and polygraphic examinations during sleep; temporal epilepsy with left or right EEG anomalies, with asynchronous bilateral EEG anomalies, with alternating labile unilateral EEG anomalies. Measurements of CBF were compared with those of normal subjects (n = 13) of comparable age and with those of epileptic patients with cerebral lesions on CT scan (n = 4). In epileptics with left EEG anomalies CBF was diminished by about 25 p. 100 in the left temporal region and from 15 to 22 p. 100 in other regions of the ipsi- and contralateral hemisphere. In epileptics with right EEG anomalies CBF was diminished by 20 p. 100 in the right temporal region but not on the left. CBF in the third group was comparable to that of normal subjects. In epileptics with abnormal CT scans the reduction in CBF could be correlated with EEG and CT scan findings. Studies were also conducted to determine variations in reactivity to CO2 in the areas with reduced flow, during ictal and interictal periods. Results emphasize the value of CBF measurements for investigation of epileptic foci. The importance of areas of reduced blood flow as a parameter of severity and course is discussed, as well as their pathophysiological significance.     

Environmental reduplication associated with right frontal and parietal lobe injury.

Four patients with environmental reduplication, a specific form of spatial disorientation and confabulation are described. The patients maintained that their hospital rooms were located in their homes. Each patients had evidence of right frontal or right parietal injury based upon computed tomography, neurosurgery, and neuropsychological testing. The factors associated with environmental reduplication were: impaired spatial perception and visual memory, inability of the patients to recognise the inconsistency between their believed location and their actual location, confusion soon after admission to hospital, and a strong desire to be at home.     

Gender differences in regional cerebral blood flow

Gender differences have been noted in neurobehavioral studies. The 133xenon inhalation method for measuring regional cerebral blood flow (rCBF) can contribute to the understanding of the neural basis of gender differences in brain function. Few studies have examined gender differences in rCBF. In studies of normal subjects, women have higher rates of CBF than men, and this is related to age. Usually by the sixth decade men and women have similar flow rates. Fewer studies on rCBF in schizophrenia have examined sex differences. The pattern of higher flows for females maintains, but its correlates with gender differences in clinical as well as other parameters of brain function remain to be examined.     

Sex differences in regional cerebral blood flow

Regional cerebral blood flow was measured by the 133-xenon inhalation method during resting in 38 healthy men and 38 healthy women matched pairwise for age in the range 18-72 years. The results showed 11% higher global flow level in the women in all ages. A similar and significant regression of flow by age was seen for both sexes. The regional flow distribution also showed some sex-related differences. Frontal regions showed an asymmetry in the men with higher values on the right side. The female flows were more symmetric. As a hypothesis, it is suggested that the higher flow level in women may be a systemic phenomenon. In fact, other authors have found a higher cardiac index in females. The sex differences in regional flow pattern might be due to differences in the functional organization of the cortex and/or to differences in the mental processes of the "resting" state.     

Sex roles and regional cerebral blood flow

Several investigators have reported higher resting cerebral blood flow (CBF) in females as compared to males. The relationship between sex roles as quantified by Bem's Sex Role Inventory and CBF was evaluated in 106 right-handed, physically and mentally healthy, drug-free volunteers. CBF was measured noninvasively with the 133xenon inhalation technique. The CBF values correlated inversely with age and positively with carbon dioxide levels, confirming previous reports. Females obtained significantly higher CBF values than males; the differences tended to be most obvious in frontal regions. Males and females who scored high on femininity showed higher CBF as compared to low-femininity subjects even after the effect of sex was covaried out. High masculine sex role tended to be associated with lower CBF, but the effect was less clear.     

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V(158)M COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls. The effects of COMT genotype on four measures of working memory/executive functions (Wisconsin Card Sorting, digit span backward, Trail Making and N-back tests) and on MRI frontal brain volumes were examined. Genotype distributions were not significantly different between patients and controls. There were no significant genotype or genotype-by-group effects on any working memory/executive function measures. No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes. Randomization analyses using [(15)O]H(2)O positron emission tomography (PET) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task. Overall, these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function. Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition.     

Vibration-induced regional cerebral blood flow responses in normal aging.

Task-induced changes in regional CBF (rCBF) can be measured with positron emission tomography (PET) and provide a powerful tool to map brain function. Many studies using these techniques have investigated responses in healthy young subjects. Since many pathological conditions occur more commonly in older subjects, it is necessary to compare blood flow responses in these patients with appropriately age-matched controls. Furthermore, the effects of normal aging on such blood flow responses remain unknown. For both reasons, we designed this study to determine whether vibration-induced CBF responses change with advancing age in normals. CBF was measured with PET and bolus-administered H2(15)O in 26 subjects from 20 to 72 years old (mean = 39; SD = 19). Regional responses were identified by subtraction-image analysis. Left and right hand vibration produced consistent responses in contralateral primary sensorimotor area (PSA) and supplementary motor area (SMA). Response magnitudes were compared to age by linear regression. There were no substantial relationships between age and responses to vibration for PSA or SMA (PSA r = -0.28, p = 0.054; SMA r = -0.33, p = 0.13). Power analysis demonstrates a high degree of confidence (99.7% for PSA and 87% for SMA) for detecting at least a moderate correlation (r = 0.6) between response magnitude and age. We conclude that the rCBF responses to vibrotactile hand stimulation do not change with normal aging.     

Regional cerebral blood flow in children--normal value and regional distribution of cerebral blood flow in childhood

The changes in CBF and rCBF through the entire age range include the rapid period in childhood was reported. Sixteen children between the ages of 1 and 15 and 14 adults were studied. These 30 subjects were either volunteers of out-patients without CT and EEG abnormalities. rCBF was measured by the 133Xe intravenous injection method using Varmet rCBF analyzer. Ther relationship between age and CBF, the correlation coefficient was calculated based on the regression equations and the regression curve with the highest correlation was chosen. For the analysis of rCBF, he mean rCBF values (ISI) of 3 channels corresponding to the frontal, temporal, parietal and occipital lobes were expressed as a percentage of the hemispheric CBF. The hemispheric blood flow (ISI and CBF gray) of children less than 5 years of age was approximately twice that found in adults. This value decreased rapidly with age and in the 10-15 years the blood flow was approximately 1.3-fold that of adults. Thereafter, there was a slow decrease and a negative correlation with age was found. The decrease showed the correlation on the following equations; y = 146.5 - 58.5 log x. (r = -0.903) for ISI and log y = 2.26 - 0.29 log x. (r = -0.881) for CBF gray, which was statistically significant. In contrast, the CBF white showed a slightly higher value in the 1-2 years old children, but thereafter the CBF did not show a notable decreases with age. Through the entire age range, a best fit for the Fw values was found with : y = 18.3 + 37.5/x. (r = 0.798), which was also statistically significant.     

Raised intracranial pressure and cerebral blood flow: 4. Intracranial pressure gradients and regional cerebral blood flow

Intracranial pressure was raised by expansion of a supratentorial subdural ballon in anaesthetized baboons. Pressures were measured at several sites, both supratentorial and infratentorial, and cerebral blood flow was measured in each cerebral hemisphere separately. Pressures recorded from the right and left lateral ventricles corresponded closely throughout. Highly significant correlations were also obtained between the pressures in the right and left subdural spaces and the mean intraventricular pressure. There was, thus, no evidence of intracompartmental pressure gradients within the supratentorial space. Pressure gradients did, however, develop between the supratentorial and infratentorial compartments in the majority of experiments, although the level of supratentorial pressure at which this occurred, varied. Despite the presence of a large mass lesion over the right cerebral hemisphere, no significant differences developed between levels of cerebral blood flow in the two hemispheres, although flow in the right hemisphere remained consistently slightly lower than that in the left after the ballon was inserted.     

血液光量子疗法对局灶性脑缺血大鼠大脑皮层局部血流量和脑水肿的影响

本文动态观测了光量子疗法治疗血栓栓塞性脑缺血大鼠,大脑皮层局部血流量(rCBF)及脑水肿的变化。结果:缺血6小时经光量子血液治疗2小时后,rCBF于注后30min明显增加,达19.78％(P<0.01),以后各点维持在一定水平,2小时增加到19.30(P<0.05)。脑组织比重:缺血中心区未见明显改善(P>0.1)而半暗区组织比重非常明显增加(P<0.001),可见水肿明显减轻。说明光量子疗法增加rCBF,减轻半暗区水肿。     

Correlation between inter-ictal regional cerebral blood flow and sphenoidal electrodes--recorded inter-ictal spikes in mesial temporal lobe epilepsy

The objective of this study was to assess the reliability of the diagnosis of mesial temporal lobe epilepsy using EEG and sphenoidal electrodes. Inter-ictal 99 m Tc-HMPAO SPECT scans were registered in 21 patients with confirmed mesial temporal lobe epilepsy identified by scalp EEG and sphenoidal electrodes. Visual and quantitative SPECT analysis was performed blind to EEG data. An asymmetry index (AI) was measured from the ratio of two symmetrical regions of interest. A temporal lobe hypoperfusion was defined as an uptake reduced by 5% with respect to the contralateral region. Inter-ictal SPECT abnormalities were observed in 12 out of 21 patients (57%) from both visual and quantitative analysis (focal hypoperfusion in 11 cases, focal hyperperfusion in one case). In seven patients (33%) both visual and quantitative scintigraphy were normal. Abnormal AI was found in 11/15 patients with a high frequency of seizures and in 1/6 patients with a low frequency of seizures. The major data is that the probability to have an abnormal SPECT is statistically correlated to the frequency of the epileptic fits. The couple EEG recordings with sphenoidal electrodes and SPECT is sensitive and reliable in the diagnosis of mesial temporal lobe epilepsy.     

Clinical symptoms and regional cerebral blood flow in schizophrenia

This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increases rCBF in bilateral anterior cingulates and decreased rCBF in bilateral midolle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.     

The regional cerebral blood flow in familial dysautonomia

Regional cerebral blood flow (rCBF) was measured during rest by the Xenon 133 inhalation method in 8 patients with familial dysautonomia (FD). The rCBF data were compared with those obtained in a group of 55 age-matched normal subjects. In 5 moderately affected patients there was a significant increase in the rCBF, while in one severely affected female, rCBF was markedly decreased. In two mildly affected patients, rCBF was normal and similar to controls. It is suggested that the increases in rCBF in FD may compensate for a yet undetermined autoregulatory failure of cerebral vasculature.