Anterior paralimbic mediation of procaine-induced emotional and psychosensory experiences.

BACKGROUND: Procaine activates limbic structures in animals. In humans, acute intravenous administration of procaine yields emotional and psychosensory experiences and temporal lobe fast activity. We studied procaine's acute effects on cerebral blood flow (CBF) in relationship to clinical responses. METHODS: Cerebral blood flow was assessed by positron emission tomography with oxygen-15-labeled water in 32 healthy volunteers. Data were analyzed with statistical parametric mapping and magnetic resonance imaging-directed regions of interest. RESULTS: Procaine increased global CBF and, to a greater extent, anterior paralimbic CBF. Subjects with intense procaine-induced fear compared with those with euphoria had greater increases in left amygdalar CBF. Absolute and normalized left amygdalar CBF changes tended to correlate positively with fear and negatively with euphoria intensity. Procaine-induced visual hallucinations appeared associated with greater global and occipital CBF increases. Absolute occipital CBF increases appeared to correlate positively with visual hallucination intensity. CONCLUSIONS: Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes.

Monitoring the source of memory in detoxified alcoholics.

The ability to monitor the source of remembered information and related reflective cognitive processes was examined in normal volunteers and detoxified alcoholics. Normal volunteers were very accurate judges of whether remembered events were presented as stimuli or were self-generated, even when memory was tested 2 days later. In contrast, a subgroup of otherwise cognitively unimpaired alcoholics demonstrated impairments in the ability to track the source of remembered knowledge and were also less able to inhibit intrusion errors in recalling information from memory. These findings provide preliminary evidence of an impairment in cognitive control functions in certain alcoholics. This conclusion is supported by associated findings indicating that, among alcoholics, performance on explicit memory tasks that required reflective cognitive operations were positively correlated with glucose utilization rates in left prefrontal, temporal, and posterior orbital frontal cortical regions.

Regional cerebral glucose metabolism in bulimia nervosa.

OBJECTIVE: The authors' purpose in this study was to further delineate the character of cerebral metabolism in bulimia nervosa and to determine if functional links could be made between regional cerebral metabolism and the symptoms of depression, obsessive-compulsive disorder, and bulimia nervosa. METHOD: Regional cerebral glucose metabolism was measured by using positron emission tomography in 11 inpatients with bulimia nervosa and 18 normal comparison subjects matched in sex (all were women), age, and educational level. The bulimic patients were also tested for symptoms of major depression and obsessive-compulsive disorder. RESULTS: The patients with bulimia showed a correlation between lower left anterolateral prefrontal regional cerebral glucose metabolism and greater depressive symptoms. However, the orbitofrontal regional cerebral glucose metabolism of patients with bulimia was not greater than that of comparison subjects, nor was higher orbitofrontal metabolism correlated with greater obsessive-compulsive disorder symptoms. CONCLUSIONS: These findings lead to the conclusion that left anterior lateral prefrontal cortex hypometabolism varies with the depressive symptoms observed in bulimia but that temporal lobe hypermetabolism and asymmetries appear to be independent of the mood state.

Cerebral glucose metabolism, CSF 5-HIAA levels, and aggressive behavior in rhesus monkeys.

OBJECTIVE: Considerable evidence suggests that low concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF are associated with a history of aggressive behavior in both human and nonhuman primates. The purpose of this investigation was to examine the relationships among CSF 5-HIAA concentration, history of aggressive behavior, and cerebral glucose metabolism in a group of nonhuman primates whose CSF 5-HIAA had been sampled several times over the preceding 2 years and whose social behavior had been observed since birth. METHOD: The subjects were nine adult male rhesus monkeys studied under isoflurane anesthesia. Cerebral glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography. Aggressiveness ratings were made by a primatologist who had had frequent contact with the animals over several years. RESULTS: There was a significant negative correlation between ratings of aggressive behavior and CSF 5-HIAA concentrations. There was also a negative correlation between the dose of pentobarbital required to induce anesthesia and level of CSF 5-HIAA. Moreover, there were significant negative correlations between CSF 5-HIAA levels and both whole brain glucose utilization and regional glucose utilization in the orbital-frontal cortex. CONCLUSIONS: These results suggest that both increased aggressiveness and low concentrations of CSF 5-HIAA are associated with higher brain glucose metabolism in rhesus monkeys under standardized anesthesia. Aggressive nonhuman primates with low CSF 5-HIAA concentrations may have "innate" tolerance toward functional gamma-aminobutyric acid A receptor agonists such as pentobarbital, isoflurane, and possibly alcohol.

Inverse relationship of peripheral thyrotropin-stimulating hormone levels to brain activity in mood disorders.

OBJECTIVE: The author's goal was to investigate relationships between peripheral thyroid hormone levels and cerebral blood flow (CBF) and cerebral glucose metabolism in affectively ill patients. METHOD: Medication-free inpatients with major depression or bipolar disorder were studied with oxygen-15 water and positron emission tomography (PET) to measure CBF (N = 19) or with [18F] fluorodeoxyglucose and PET to measure cerebral glucose metabolism (N = 29). Linear regression was used to correlate global CBF and cerebral glucose metabolism with serum thyrotropin-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and free T4 concentrations. Statistical parametric mapping was used to correlate regional CBF and cerebral glucose metabolism with these thyroid indexes. Post hoc t tests were used to further explore the relationships between serum TSH and global CBF and cerebral glucose metabolism. RESULTS: Serum TSH was inversely related to both global and regional CBF and cerebral glucose metabolism. These relationships persisted in the cerebral glucose metabolism analysis and, to a lesser extent, in the CBF analysis after severity of depression had been controlled for. In contrast, no significant relationships were observed between T3, T4, or free T4 and global or regional CBF and cerebral glucose metabolism. CONCLUSIONS: These data suggest that peripheral TSH (putatively the best marker of thyroid status) is inversely related to global and regional CBF and cerebral glucose metabolism. These findings indicate relationships between thyroid and cerebral activity that could provide mechanistic hypotheses for thyroid contributions to primary and secondary mood disorders and the psychotropic effects of thyroid axis manipulations.

Positron-emission tomography and personality disorders.

This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively.

The ratio of mesial to neocortical temporal lobe blood flow as a predictor of dementia.

OBJECTIVE: The hypothesis tested was that an increased ratio of cerebral blood flow (rCBF) in the mesocortical temporal lobe to that of the neocortical temporal lobe (MES/ NEO ratio) would be related to clinical measures of dementia severity and would help distinguish Alzheimer's patients from normal controls. DESIGN: The rCBF of nine Alzheimer's patients (5 males and 4 females; age = 65.9 +/- 6.0 years, range 55-71; Folstein Mini-Mental Status Examination = 18.6 +/- 7.4, range 9-28) and 10 age-matched normal controls (7 males, 3 females; age = 66.0 +/- 5.7 years, range 58-75) was determined by positron emission tomography (PET) using H2(15)0 and the method of Alpert et al. RESULTS: Alzheimer's disease patients had a significantly higher MES/NEO ratio (1.19 +/- .17) than the age-matched normal controls (.854 +/- .14; t = .-4.74, df = 17, P = .0002). Using a MES/NEO ratio of 1 as the cutoff point for discrimination between Alzheimer's patients and normal controls, the ratio demonstrated 100% sensitivity (no. of correctly identified Alzheimer's patients/no. of Alzheimer's patients) and 90% specificity (no. of correctly identified unaffected subjects/no. of unaffected subjects). Further, those patients with the highest MES/NEO ratios had the lowest overall measures of cognitive function (Folstein Mini-Mental Status Examination: r = -.75, P < .02, 1-tail; Mattis Dementia Rating Scale: r = -0.655, P = .028, 1-tail) scores. CONCLUSIONS: The findings are consistent with other in vivo and postmortem studies, suggesting that functional and structural changes of the lateral temporal lobe in Alzheimer's disease occur relatively early in the disease process and appear to be distinguishable from those changes accompanying normal aging. In contrast, the memory loss and pathology of the mesial temporal lobe that is characteristic of the early stages of Alzheimer's patients do not appear to be associated with a reduction in cerebral blood flow in the resting Alzheimer's patient. Nevertheless, the clinical significance of the results must await findings of longitudinal studies of larger numbers of Alzheimer's patients and controls.

Opiate receptor avidity and cerebral blood flow in Alzheimer's disease.

Positron emission tomography was performed on 12 Alzheimer's patients and 12 age-matched normal controls following the administration of the opiate receptor antagonist 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF). Tracer kinetic analysis was used to determine the volume of distribution of CF, a measure of unoccupied mu and kappa receptor density, i.e. opiate receptor avidity in 34 brain regions. Regional cerebral blood flow rates (CBF) were determined on the same day with H2[15O]. Global gray CF avidity and global gray CBF were found to be lower in the Alzheimer's patients and correlated (r=0.73, P<0.03). Regional CBF differences were superimposed on global CBF changes in the Alzheimer's patients, with the subcortex relatively spared. Multivariate statistical analyses, however, failed to demonstrate regional specificity for the CF avidity changes. Furthermore, percent changes in regional CF avidity were not correlated with percent changes in regional CBF (r=0.12, P=NS). These findings demonstrate involvement of the opiate system in Alzheimer's disease. Although, neurodegeneration is the likely underlying process responsible for both the changes in CF avidity and CBF in Alzheimer's disease, the differences with respect to the patterns of these losses suggest that the intermediate mechanisms leading from neurodegeneration to loss are distinct.

Head motion during positron emission tomography: is it significant?

High sensitivity for detecting local brain function differences from subsequent PET images acquired at different cerebral stimulation states requires interscan head motion to be minimized. This motion was measured by an optical lever system during scanning (130 min) of 15 subjects in a dual-dose injection study. Despite motion restriction by a face-mask restraint system, rotations in the sagittal and coronal planes (up to 4.1 degrees and 2.4 degrees, respectively) significantly influenced the measured means and variances of local metabolic differences between states. Hence, adjustments for head movement by retrospective, digital slice realignment or, better, real-time corrections are important.

Gender-related differences in regional cerebral glucose metabolism in normal volunteers.

Positron emission tomography studies have correlated changes in the cerebral metabolic rate of glucose utilization (CMRglu) with symptoms of depression, aggression, impulsivity, and hyperactivity. Psychiatric disorders in which these symptoms are manifested are disproportionately represented among the sexes. We evaluated gender differences in regional CMRglu in control subjects (21 men and 18 women) with particular interest in the global, orbital frontal, and left anterolateral prefrontal cortical (LAPFC) CMRglu. A trend was present for global CMRglu to be greater in women than in men. Regional CMRglu was lower in men than in women in the orbital frontal area. No differences were observed in the LAPFC region.

Effects of triazolam and ethanol on proactive interference: evidence for an impairment in retrieval inhibition.

The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list (e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task.

Wisconsin Card Sorting Test performance following head injury: dorsolateral fronto-striatal circuit activity predicts perseveration.

The Wisconsin Card Sorting Test (WCST) has been argued to be a sensitive indicator of frontal lobe function. However, several recent studies have failed to find a consistent relationship between structural damage to this cortical area and perseveration on the test. In the present study, positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose was used to examine the relationship of regional brain metabolism to perseverative responding on the WCST in patients with a history of closed-head injury. An inverse relationship was found between perseverative responses and metabolism in the right, but not the left, dorsolateral prefrontal cortex and caudate nucleus. Perseverative responding was not related to metabolism in several other regions of the frontal lobes and basal ganglia, including the putamen and the frontal poles bilaterally. These data suggest that the functional integrity of the right dorsolateral frontal-subcortical circuit is critical for WCST performance.