Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method.

Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found.

Sylvian fissure asymmetries in monozygotic twins: a test of laterality in schizophrenia.

To address prior reports that schizophrenia is associated with loss of normal brain asymmetry and that it might be linked to a defect of a gene controlling cerebral lateralization, we measured on three-dimensional cortical renderings from magnetic resonance imaging (MRI) scans the lengths and angles of the sylvian fissures in 10 normal monozygotic (MZ) twin pairs (n = 10 pairs) and in 10 MZ pairs discordant for schizophrenia (n = 10 pairs). We confirmed in both sets of twins the expected normal asymmetries of length and angle of the sylvian fissure. We also confirmed that the length asymmetry occurs solely in the region of the planum temporale. In the discordant twins, affected and unaffected twins did not differ in asymmetry measures, thus failing to support an association between illness per se and diminished asymmetry. Moreover, the discordant twins as a group did not differ from the normal twins as a group, thus failing to confirm the hypothesis of a genetic association with abnormal asymmetry. The implications of variations in methodology and patient samples are discussed.

Regional cerebral blood flow during the Wisconsin Card Sorting Test in normal subjects studied by xenon-133 dynamic SPECT: comparison of absolute values, percent distribution values, and covariance analysis.

We studied regional cerebral blood flow (rCBF) by xenon-133 dynamic single photon emission computed tomography (SPECT) in 17 normal volunteers who were performing the Wisconsin Card Sorting Test (WCST), a task that is particularly sensitive to disturbance of the prefrontal cortex, and a simple matching-to-sample task (BAR) as a sensorimotor control. Three methods for statistical analysis of regional "subtraction" data were used: absolute rCBF values, percent distribution values, and means adjusted for global CBF changes (covariance analysis). The absolute values had high variance, due to the combination of interindividual differences in global flow and intra-individual variation, and showed no statistically significant regional changes. This variation was greatly reduced by percent values and covariance analysis, which had quite similar outcomes. With both methods, significant increases of rCBF during the WCST as compared with the BAR were seen in the right anterior dorsolateral prefrontal and left occipital cortices, and reduction of rCBF in the left pararolandic region. Moreover, significant correlations with performance were found in the medial regions of the frontal lobes, with opposite trends for the right and left hemisphere. The posterior dorsolateral prefrontal region showed a negative correlation with sensory-motor frequency, an index related to the task's difficulty. These results are consistent with previous findings using other rCBF techniques and confirm the statistical advantage of normalization and covariance methods, which yield practically identical results, at least in this analysis based on regions of interest.

Measurement of brain activity with bolus administration of contrast agent and gradient-echo MR imaging.

This study was performed to measure changes in cerebral blood volume (CBV) associated with visual activation by use of bolus administration of contrast agent and conventional, clinically configured magnetic resonance (MR) hardware and software. Fast gradient-recalled acquisition in the steady state technique was used to study five healthy subjects during visual activation and a control dark state. MR images were obtained every 2.048 seconds for 2 minutes. A bolus of gadopentetate dimeglumine was injected during visual stimulation and darkness. Cine images produced from the series of rapid images clearly depicted arterial, capillary, and venous phases. Analysis of serial concentration maps derived from the rapid images revealed expected differences between the relative CBV of gray matter and that of white matter, as well as significantly increased relative CBV in calcarine cortex during visual activation versus the control state (mean increase, 15.24%; range, 6.41%-27.78%; P < .05). These results confirm those reported in echo-planar imaging studies and demonstrate that brain function can be assessed with the bolus method by means of MR imaging hardware and software with conventional clinical configurations.

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.

The Psychiatric Consultation Checklist: a structured form to improve the clarity of psychiatric consultation requests.

Medical specialty consultation is requested to obtain expert review of a patient's condition. The specialist usually receives a case synopsis with pertinent positives and negatives and a specific request for assistance. In contrast, the psychiatrist often gets a statement of diagnostic speculation (e.g., "depressed") with a request to "please evaluate." Classically, the psychiatric consultant begins with open-ended empathic questioning in an attempt to redefine the written consultation question. However, given the difficulty consultees have in forming questions, and increasing time limitations, a more structured approach to obtaining data might assist both the consultee (M.D. requesting assistance) and the consultant (psychiatrist). The Psychiatric Consultation Checklist (PCC) was devised to function as a paper "expert" questioning system to provide such assistance. In a pilot study, 10 administrations of the PCC took an average of 3.6 minutes. In comparison to consultations using standard forms, more data were supplied in several categories when the PCC was used, particularly regarding patient stressors, patient behaviors of concern, and consultee speculation on psychiatric diagnostic formulation. The PCC may be used in consultation research, for assessment and education of physicians in training (regarding psychiatric issues in the medical/surgical setting), and for general clinical consultation purposes.

Comparison of two alpha-noradrenergic agonists (clonidine and guanfacine) on norepinephrine turnover in the cortex of rats during morphine abstinence.

The effects of the alpha-agonists clonidine and guanfacine on rat cortical norepinephrine turnover during morphine withdrawal were assessed. Cortical norepinephrine levels were measured, after administration of alpha-methyl-p-tyrosine, by fluorometric assay. Chronic treatment with morphine did not affect norepinephrine levels or norepinephrine turnover. In control animals, doses up to 200 micrograms/kg clonidine and 1060 micrograms/kg guanfacine did not affect norepinephrine steady state levels, but did reduce alpha-methyl-p-tyrosine-induced norepinephrine depletion. As little as 5 micrograms/kg clonidine reversed the accelerated turnover observed during naloxone precipitated morphine withdrawal; while for guanfacine, the minimum effective dose was 212 micrograms/kg. the ED50 for guanfacine's reversal of the withdrawal-induced acceleration of turnover was approximately 60 times that for clonidine.

Presynaptic dopamine receptors: insensitivity to kainic acid and the development of supersensitivity following chronic haloperidol.

The effects of kainic acid lesions and chronic haloperidol treatment on rat striatal dopaminergic presynaptic receptors were studied. Following the gamma-butyrolactone-induced inhibition of dopaminergic impulse flow, and after dopa decarboxylase inhibition, dopa accumulation and its reversal by dopamine agonists was measured in vivo. 3H-apomorphine (a dopamine receptor ligand with purported presynaptic specificity) was used for in vitro binding experiments. Presynaptic dopamine receptors, as assessed by both methods, were unaffected by intrastriatal kainic acid injection 5-6 days before sacrifice. Seven days after termination of chronic haloperidol treatment (28 days, 0.5 mg/kg/day s.c.) both an increased apomorphine response using the dopa accumulation method and an increase in 3H-apomorphine binding were observed, indicating the development of presynaptic dopamine receptor supersensitivity.