Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence

OBJECTIVE: The purpose of the study was to determine the effects of cigarette smoking on brain regional function in a group of chronic smokers by using cerebral blood flow (CBF) measures and positron emission tomography (PET). METHOD: Nineteen tobacco smokers were studied after about 12 hours of smoking abstinence. Regional CBF (rCBF) measures were obtained with PET and [15O]H2O in six consecutive scans. Two average-nicotine-yield (1.0 mg) and one denicotinized (0.08 mg) research cigarettes with similar tar yields (9.5 mg and 9.1 mg, respectively) were smoked in a double-blind design, preceded and followed by baseline scans. The rCBF effects of smoking were compared to baseline measures and between cigarettes, as well as to subjective ratings of craving for cigarettes. RESULTS: Smoking the first cigarette of the day resulted in increases in rCBF in the visual cortex and the cerebellum and reductions in the anterior cingulate, the right hippocampus, and the ventral striatum, including the nucleus accumbens. Cigarette craving scores correlated with rCBF changes in the dorsal anterior cingulate and right hippocampus. Less pronounced effects were observed with the second cigarette and the denicotinized cigarette. CONCLUSIONS: Smoking affects rCBF not only in areas of the brain rich in nicotinic cholinergic receptors but also in areas implicated in the rewarding effects of drugs of abuse. Furthermore, craving for a cigarette in chronic smokers was correlated with rCBF in the right hippocampus, an area involved in associating environmental cues with drugs, and in the left dorsal anterior cingulate, an area implicated in drug craving and relapse to drug-seeking behavior.     

Regional cerebral blood flow after marijuana smoking.

Regional CBF was measured with the 133Xe inhalation technique before and thrice after smoking marijuana of two strengths and placebo in 20 physically and mentally healthy male volunteers with a previous history of exposure to marijuana. They were drug-free at the time of the study. Blood pressure, pulse rate, end-tidal carbon dioxide, end-tidal carbon monoxide, and forehead skin perfusion were quantified during the CBF measurements. Blood samples were drawn for quantification of plasma levels of delta 9-tetrahydrocannabinol (THC) before and during the 2 h after smoking marijuana or placebo. Drug-induced intoxication and changes in mood were quantified with rating scales. Marijuana smoking was associated with bilateral CBF increase, which was maximal 30 min later. Greater CBF increases were seen in the frontal region and right hemisphere. No significant CBF changes were seen after placebo. Pulse rate and respiration increased significantly after marijuana but not placebo. Both marijuana and placebo smoking were associated with increased end-tidal carbon monoxide. CBF increase in both hemispheres correlated significantly with degree of intoxication, plasma levels of THC, and pulse rate.     

Regional cerebral blood flow effects of nicotine in overnight abstinent smokers.

BACKGROUND: Most people agree that dependence to tobacco is mediated by the effects of nicotine on the central nervous system, albeit the neural pathways involved are not clearly delineated. We investigated the effect of nasal nicotine spray on regional cerebral blood flow (rCBF) in a sample of habitual smokers, with H2 15O and positron emission tomography (PET). METHODS: Eighteen volunteer smokers were studied after 12 hours of smoking deprivation. Regional cerebral blood flow measures were obtained with PET and 50 mCi H2 15O in six consecutive scans. Nicotine spray and a placebo spray were administered in a single-blind design, preceded and followed by baseline studies. Images were coregistered and anatomically standardized. Square (9-mm side) regions of interest were placed in 10 preselected brain regions, bilaterally. The effects of the experimental condition and gender were tested with two-way repeated-measures analysis of variance in each of the regions studied. RESULTS: Nicotine reduced rCBF in the left anterior temporal cortex and in the right amygdala. Increases were noted in the right anterior thalamus. CONCLUSIONS: In habitual smokers after overnight abstinence, nicotine induced differing effects on regional blood flow relative to whole brain blood flow. Increases were observed in the thalamus, a region rich in nicotinic receptors, and reductions in limbic and paralimbic (amygdala, anterior temporal cortex) regions.     

Regional cerebral blood flow after occlusion of the middle cerebral artery

Occlusions of the middle cerebral artery (MCA) are mostly of embolic origin (appr. 80%) and give rise to about one third of all ischemic strokes, most of these being major strokes. MCA occlusions lasting for less than 1/2 h are tolerated without occurrence of permanent tissue damage. Occlusions lasting between 1/2 h to 4-8 h lead to permanent tissue damage and neurological deficits that are proportional to the duration of occlusion. Maximal tissue damage is obtained after 4-8 h occlusion. A cerebral blood flow of 8-23 ml/100 gr/min is sufficient for cellular viability but insufficient for normal tissue function ("ischemic penumbra"). Cellular function is completely abolished in the interval 8-16 ml/100 gr/min and flow at that level is tolerated only for 1-3 h before neuronal death ensues. In the interval 18-23 ml/100 gr/min there is some functional activity although it is reduced. Experimental and clinical evidence suggests that flow in this interval may be tolerated for several days, months or even longer ("chronic ischemic penumbra"). After MCA occlusion the blood flow falls below 8 ml/100 gr/min in most cases and permanent MCA occlusion always leads to relatively large areas of frank infarction. The ischemic infarcts may be surrounded by collaterally perfused areas where the blood flow is pressure-dependent (impaired autoregulation) and quite commonly insufficient for normal neuronal function (below 23 ml/100 gr/min). Such collaterally perfused areas may include a "chronic ischemic penumbra". Emboli causing MCA occlusions commonly disintegrate and/or migrate more peripherally within the first few weeks post stroke. This leads to reperfusion and changes of ischemic infarcts into hyperemic infarcts where flow is severely increased. The vascular reactivity is completely abolished in hyperemic infarcts and the hyperemic state lasts for about two weeks. Probably, anemic infarcts are equivalent to ischemic infarcts while the hemorrhagic variety is equivalent to hyperemic infarcts. The "partial infarct" with selective neuronal necrosis occurs in experimental animals after MCA occlusions of less than four h but not after permanent MCA occlusion. The significance of partial infarction in human stroke is not clarified. The extent of irreversible tissue damage can be reduced only if therapy sets in within 4-8 h after the occlusion. If a "chronic penumbra" exists the extension of reversible tissue damage can be reduced if therapy aimed at increasing the blood flow in the penumbra sets in within weeks or even months after the stroke.(ABSTRACT TRUNCATED AT 400 WORDS)     

Regional cerebral blood flow after recovery from bulimia nervosa

When ill, women with bulimia nervosa (BN) show alterations of regional cerebral blood flow (rCBF). In this study we investigated rCBF in nine women in long-term recovery from BN (RBN, n=9), i.e. more than 1 year without bingeing/purging behavior, normal weight, stable food intake, and regular menses, and compared them with age-matched healthy control women (CW, n=13). Positron emission tomography (PET) was used for the assessment of rCBF. There were no significant differences in rCBF between groups. However, rCBF was significantly inversely related to length of recovery in RBN for the left and right prefrontal cortex (BA 10), right medial orbital frontal cortex (BA 11), left subgenual cingulate (BA 25), right anterior cingulate (BA 32), left sensory motor cortex (BA 1,2,3,4), left and right lateral temporal (BA 21), and left occipital cortex (BA 17), as well as left thalamus. This finding suggests that previously reported alterations in rCBF during the ill state of BN may be a state-related phenomenon that remits with recovery. It is also possible that reductions in rCBF occur in a later stage of recovery from BN.     

Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration.

OBJECTIVE: The aim of this study was to examine the relationship between depersonalization induced by tetrahydrocannabinol (THC), and regional brain activation. METHOD: Cerebral blood flow (CBF) was measured by means of positron emission tomography (PET) in 59 normal right-handed volunteers before and following intravenous infusions of THC. RESULTS: After THC, CBF showed a global increase which was more marked in the right hemisphere, frontal lobes and anterior cingulate. CONCLUSION: Regression analyses showed positive correlations between the right frontal and anterior cingulate and depersonalization.     

Regional cerebral blood flow changes in depression after electroconvulsive therapy

A large number of studies have documented regional cerebral blood flow (rCBF) abnormalities in depression. A smaller yet significant number of studies have examined changes in rCBF before and after treatment. The findings, however, have been variable with regard to changes before and after electroconvulsive therapy (ECT). A consecutive series of patients (n=10) with drug-resistant major depressive episode according to DSM-IV with 17-item Hamilton Rating Scale for Depression (HRSD) scores greater than or equal to 14 gave their informed consent and were studied with technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (99mTc-ECD SPECT) before and after a course of ECT. The results were analyzed with statistical parametric mapping version 99. No region showed significant positive correlations between rCBF patterns of changes and HRSD changes, but three clusters emerged as showing significant negative correlations. These regions corresponded with left frontopolar gyrus, left amygdala, globus pallidus and nucleus accumbens, and left superior temporal gyrus. It was speculated that ECT affected both the prefrontal cortex, commonly assumed to be involved in depression, and the amygdala, known to play a central role in the processing of emotional stimuli, through the limbic-cortical-striatal-pallidal-thalamic circuit.     

Regional cerebral blood flow, diaschisis, and steal after stroke

Regional CBF was measured by 133Xe inhalation in unilateral cerebral infarction, carotid TIAs, and normal volunteers. Regional CBF values were bilaterally and symmetrically reduced in patients measured within 3 weeks after stroke. Later, rCBF values returned toward normal in the contralateral hemisphere of patients with infarction and in both hemispheres with carotid TIAs. In cases with carotid occlusive disease, flow reduction was seen in the contralateral posterior cerebral artery distribution, with hyperemia in ipsilateral occipital lobe caused by interhemispheric steal. Brainstem-cerebellar flow values were increased following acute cerebral infarction if patients were alert but reduced if consciousness was impaired.     

Regional cerebral blood flow after long-term exposure to carbon disulfide

Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43-65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide.     

Regional cerebral blood flow in depression

In the review article, the results of studies on regional cerebral blood flow (rCBF) in major depression are presented. Most studies have reported global and regional deficits in cerebral blood flow in major depression as compared to healthy controls. Longitudinal studies show that after recovery from depression an increase of CBF has been observed. The influence of different biological treatment methods on rCBF is also discussed. Findings regarding lateral asymmetries of cerebral function in patients with major depression are inconclusive but the deficit of rCBF is often more pronounced in the left hemisphere. The nature of regional brain flow abnormalities in depression is unclear. Structural changes of the brain and biochemical abnormalities are under consideration.     

Regional cerebral blood flow and histopathologic changes after middle cerebral artery occlusion in rats

Changes in regional cerebral blood flow were correlated with the distribution of histopathologic signs of brain injury in 35 rats after middle cerebral artery occlusion. Rats were allowed to survive for periods of up to 4 weeks after the operation, and we focused particular interest on the time course of blood flow changes from the initial ischemic events to the late stage of infarction. Regional blood flow was measured using [14C]iodoantipyrine and a quantitative autoradiographic technique. Blood flow in regions with histologic signs of infarction (i.e., the lateral caudoputamen and adjacent neocortex) was below 0.238 ml/g/min, corresponding to 15% of normal values for those regions. In perifocal regions without infarction such as the medial caudoputamen and globus pallidus, cerebral blood flow was also reduced, but it never declined below 20% of its normal value. The decrease in cerebral blood flow was most marked during the first hours after occlusion. Thereafter, cerebral blood flow values gradually normalized, and at 4 weeks there were no significant differences compared with the contralateral side. The border between cortical regions with hypoperfusion and normal cerebral blood flow was rather sharp in the coronal plane, but in the sagittal plane there was a more gradual transitional region. The region with hypoperfusion, observed in the sagittal plane, was most widespread in the acute stage, and normalization of flow occurred particularly from anterior and posterior cortical regions toward the ischemic focus. The possibility for penumbral conditions in the cortex thus exists, particularly in the anterior and posterior borders of the infarction, and remains for several hours after the initial insult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral blood flow in depression

Regional cerebral blood flow (rCBF) was measured in patients with endogenous depression by the single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I]iodoamphetamine (IMP). The subjects were 32 patients with endogenous depression and 20 normal controls. These 32 patients, who were divided into 10 unmedicated group and 22 medicated group, were reexamined when the depressed patients reverted to a euthymic state (remission). The value of rCBF was assessed by the corticocerebellar ratio (CCR), which was expressed as a ratio of activity per pixel in the cerebral regions of interests (ROIs) to the activity per pixel in the cerebellum. The depressive patients showed a decrease in rCBF all over the cerebral regions and, especially, the lower rCBF in the left than in the right hemisphere. These changes turned toward normal in a remitted state following treatments, though there was no significant difference in rCBF between the medicated and unmedicated patients. There was a significantly negative correlation between the severity of depressive symptoms and the mean rCBF in a total of patients with depression. These results suggest that psychiatric symptoms in the depressive patients might be related to the left hemispheric dysfunction.     

Regional cerebral blood flow in neuropsychology

Measurements of regional cerebral blood flow (rCBF) provide information about the metabolic and functional level of the cortex. Different techniques for measurement of rCBF are described and their potentials and limitations are outlined. Typical results from measurements in normals during performance of mental tasks are shown and as well as clinical measurements in patients with organic dementia. Future improvements of the techniques regarding spatial as well as temporal resolution are outlined. It is concluded that measurements of rCBF are likely to be of great value in the future exploration of brain-behaviour relationships.     

Regional cerebral blood flow in parkinsonism: Measurement before and after levodopa

Data from recent studies in experimental animals suggest that central dopaminergic mechanisms may be involved in regulation of the regional cerebral blood flow (rCBF) in the mammalian brain. In order to evaluate possible effects of dopaminergic stimulation on human cerebral circulation, rCBF was measured by the ¹³³Xenon inhalation technique in 26 patients with Parkinson's disease before and after the chronic oral administration of levodopa combined with a peripheral Dopa-decarboxylase inhibitor. Treatment with levodopa did not induce significant alterations in the mean brain, mean hemispheric or regional flow values in these patients. These findings suggest that the dopaminergic system does not play an important role in modulation of the rCBF in man.     

Regional cerebral blood flow in Down's syndrome

Regional cerebral blood flow was measured in 14 patients with Down's syndrome, in 46 patients with Alzheimer's disease and senile dementia of the Alzheimer type, and in 114 age-matched controls, using the xenon 133 inhalation technique. Cerebral blood flow was reduced in 13 of 14 Down's patients by a mean of 16.8 +/- 2.5% from expected age-matched normal values. Degrees of regional cerebral blood flow reduction did not differ among the frontal, temporal, parietal, and occipital regions in both cerebral hemispheres. The regional cerebral blood flow decreases were similar in magnitude and pattern to those in Alzheimer patients. These findings constitute an additional similarity between the two disorders.     

Regional cerebral blood flow in depression and mania

Forty-three depressed inpatients, referred for electroconvulsive therapy, and 30 manic patients were examined with clinical ratings and regional cerebral blood flow (rCBF) determinations. The depressed patients were mainly medication free, while most of the manic patients were medicated. Both patient groups showed a normal cerebral blood flow level and regional distribution compared with age- and sex-matched normal controls. In the depressed group and especially in the unipolar subgroup, a significant positive relationship was found between the mean rCBF and symptoms of depression and cognitive dysfunction. Eighteen of the depressed and 18 of the manic patients were reexamined in a euthymic state following treatment and recovery. Only minor and statistically nonsignificant flow changes were found in connection with the clinical improvement. In the manic patients, a significant negative relationship was found between neuroleptic dosage and rCBF.     

Regional cerebral blood flow in developmental stutterers

Stuttering is a poorly understood communication disorder with a 1% global prevalence. Recently, there has been a resurgence of interest in a neurogenic origin for the disorder, although no research has established clear neurological differences between "developmental" (stuttering onset in childhood) stutterers and nonstutterers. We have used xenon 133 single-photon emission computed tomography to study regional cerebral blood flow (rCBF) in 20 stutterers. Analysis revealed global, absolute flow reductions. Relative flow asymmetries (left less than right) were identified in three hemispheric regions: anterior cingulate and superior and middle temporal gyri. Milder changes were found in the left inferior frontal gyrus. Stutterers had rCBF values below median for either anterior cingulate or middle temporal gyri. With one exception, severe stutterers had rCBF values below median for the anterior cingulate gyrus. All stutterers with rCBF values above median in the cingulate gyrus had rCBF values below median in the middle temporal gyrus, and severity of their disorder was either mild or moderate. Our findings suggest that stuttering is a neurogenic disorder involving recognized cortical regions of speech-motor control.     

Regional cerebral blood flow in schizophrenic disorders

Regional cerebral blood flow was measured using a 133Xe inhalation technique in 16 schizophrenic patients and 20 healthy volunteers. The bilateral frontal blood flows in the patient groups were significantly lower than in the control group. In addition, the patient group having auditory hallucination showed a significantly increased blood flow predominantly in the left temporal region. On the other hand, the patient group without auditory hallucination showed a slightly increased flow in the right temporal region. These findings indicate that there are a hypofrontal activity and also a hypertemporoparietal activity in schizophrenics.     

Regional cerebral blood flow decreases during hyperglycemia

The presence of hyperglycemia before brain ischemia increases stroke-related morbidity and mortality in experimental animals and humans. However, little is known of the effect of hyperglycemia on regional cerebral blood flow (rCBF). Acute hyperglycemia was induced in awake but restrained rats by intraperitoneal injection of 50% D-glucose. Regional flow was determined using [14C]iodoantipyrine and quantitative autoradiography. Elevation of plasma glucose from 11 to 39 mM was associated with a 24% reduction in rCBF when compared with controls that received normal saline. Intraperitoneal D-mannitol produced an elevation of plasma osmolality equivalent to that observed with glucose. However, rCBF was only reduced by 10%. Hyperglycemia appears to produce a global decrease in rCBF in awake rats that cannot be completely explained by the attendant increase in plasma osmolality. If a similar influence is present during brain ischemia, hyperglycemia could extend areas of critical flow limitation.