Paul Andreason

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 procaines 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.

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.

A functional lesion in developmental dyslexia : Left angular gyral blood flow predicts severity

Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p <.01), but with worse reading skill in dyslexia (p <.01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia.

Reproducibility of Resting Cerebral Blood Flow Measurements with H215O Positron Emission Tomography in Humans

Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using H215O positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g−1 min−1, mean ± SD) for the first (40.3 ± 6.4) and second (39.3 ± 6.5) measurements was not significantly different (mean % difference 2.3 ± 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left-right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans.

Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorder

BACKGROUND Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients. METHODS An independent group of panic disorder patients placed on imipramine was studied with positron-emission tomography, testing for evidence of normalization versus persistence of the abnormal rCMRglc ratios. Differences in orbital frontal rCMRglc values between the imipramine-treated and the previously reported unmedicated panic disorder patients were tested examining for evidence that the differences would resemble those noted in obsessive-compulsive disorder (OCD) patients treated with clomipramine. RESULTS We found the same abnormally low L/R hippocampal and posterior inferior prefrontal rCMRglc ratios in the imipramine-treated panic disorder patients. In addition, we found posterior orbital frontal rCMRglc decreases in the imipramine-treated panic disorder patients compared with the unmedicated panic disorder patients. CONCLUSIONS These abnormal asymmetries found in unmedicated panic disorder patients and now in imipramine-treated panic disorder patients may reflect a trait abnormality. The orbital frontal rCMRglc differences between the imipramine-treated and unmedicated patients are similar to changes noted in OCD patients treated with clomipramine and may reflect direct or indirect effects of imipramine treatment in panic disorder patients.

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

Positron emission tomography was performed on 12 Alzheimers 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 Alzheimers patients and correlated (r=0.73, P<0.03). Regional CBF differences were superimposed on global CBF changes in the Alzheimers 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 Alzheimers disease. Although, neurodegeneration is the likely underlying process responsible for both the changes in CF avidity and CBF in Alzheimers 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.

Procaine-induced increases in limbic rCBF correlate positively with increases in occipital and temporal EEG fast activity.

SummaryPrevious independent EEG and PET studies suggest that administration of intravenous procaine hydrochloride selectively activates limbic brain structures. To further elucidate procaines effects and explore the relationship between quantitative EEG (qEEG) and regional cerebral blood flow (rCBF), we simultaneously recorded qEEG and sampled rCBF using O-15 water PET in 20 healthy volunteers during single-blind injections of saline (baseline condition) followed by intravenous procaine (1.84 mg/kg). After thorough screening of EEG records, a subgroup of 7 subjects with EEG data relatively free of both muscle and movement artifacts was selected for analysis. Quantitative spectral EEG data from right occipital and temporal leads were then correlated with each subjects PET rCBF values on a pixel by pixel basis, both at baseline and after procaine. The most striking finding was that the increases in occipital and temporal omega activity from baseline to procaine positively correlated with rCBF increases in the amygdala and its efferents (p<.05), in a pattern very similar to the rCBF increases seen after procaine administration. This suggests that omega activity may reflect activation of deeper brain limbic structures. Also, the convergence of EEG and PET data further supports procaines selective limbic activation.

Right frontotemporal activation by tonal memory in dyslexia, an O15 PET study

A prior study documented the failure of dyslexic men to activate left temporoparietal cortex during phonologic processing. Because of reports of an anomalous right planum temporale in developmental dyslexia, the functional implications of which are unknown, this study examined the ability of dyslexics to activate right temporal cortex. Regional cerebral blood flow was measured in 15 right-handed dyslexic men during rest and during a tonal memory task expected to activate right-sided cortex in controls. A matched control sample (n = 18) showed significant activation of several right frontotemporal regions as well as of left temporal cortex. In contrast, severely dyslexic men activated fewer right frontotemporal regions, while making many more errors than controls, but showed normal activation of left mid to anterior temporal cortex. These results support hypothesized underlying deficits in rapid temporal processing and possible involvement of right (in addition to left) temporal cortex in severe dyslexia.

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.