Annamaria Berardi

Brain mechanisms in human classical conditioning: a PET blood flow study.

Five healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. 15OPET scans were taken during the habituation and extinction phases. Because the habituation and extinction phases were similar, any difference in blood flow to the tones presented during extinction probably reflected conditioning that occurred during the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET data showed significantly increased activation in the right hemisphere in the orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal corticies, and inferior and middle temporal corticies. The only activated areas in the left hemisphere were area 19 and the superior frontal cortex. The results are interpreted as evidence for the involvement of cortical areas in human classical conditioning.

Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer's disease

Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimers disease. During dose finding, performance on a verbal memory task improved with an inverted U-shaped relation to dose. Six of nine subjects were classified as responders. During blinded, placebo-controlled, individualized optimal dosing for 5 days, verbal memory again improved in five of six responders but not in any non-responder. No adverse drug effects occurred. Arecoline, and possibly other cholinergic agonists, can safely improve memory in Alzheimers disease at doses much lower than previously studied.

Clinical pharmacokinetics of arecoline in subjects with Alzheimer's disease

To study the pharmacokinetics and pharmacodynamics of intravenously administered arecoline in subjects with Alzheimers disease.

Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer's disease

Nine patients with possible or probable dementia of the Alzheimer type were tested on nine cognitive tests prior to (two times) and during continuous intravenous administration of five different doses of the muscarinic cholinergic agonist arecoline (1, 4, 16, 28, and 40 mg/day). The present analysis examined whether improvement on cognitive testing for each patient during arecoline treatment was most likely to occur at the same dose for all tests or whether different test scores improved at different doses of arecoline. Results indicated there were significant differences among tests in the dose at which most patients showed improved cognitive performance. These differences may have therapeutic significance, as verbal ability tended to improve at low doses of arecoline, whereas attention and visuospatial ability tended to improve at higher doses of arecoline.

Imagery and hypnotizability revisited.

The objective of this study was to correlate computer-generated imagery tasks and a self-report measure of imagery ability with hypnotizability, hypothesizing that computer-generated imagery tasks would be better predictors of hypnotizability than will the self-report measure. Hypnotizability of 43 subjects was assessed using the Hypnotic Induction Profile and the Stanford Hypnotic Susceptibility Scale, Form C. Imagery ability was assessed by the Visual Vividness Imagery Questionnaire (VVIQ) and by computer-generated imagery tasks measuring the ability to generate, maintain, and transform images. Although there was no correlation between the VVIQ and hypnotizability, the less hypnotizable subjects made twice as many mistakes in the spatial imagery tasks than did the more hypnotizables, but this difference was not statistically significant. The relationships among hypnotic performance, hypnotizability, and imagery functions are complex.

Treatment of Alzheimer disease by continuous intravenous infusion of physostigmine

Summary Physostigmine, a reversible and nonselective cholinesterase inhibitor, administered by steady-state, continuous intravenous infusion to carefully selected subjects with mild-moderate Alzheimer disease, produced significant but modest improvement in memory in five of nine subjects. Drug dosing was limited by the occurrence of adverse effects. Apparent tolerance to adverse effects was observed in two subjects when the dose of physostigmine was escalated slowly over at least 2 weeks. Steady-state cholinesterase inhibition by physostigmine appears to produce sustained cognitive improvement in some subjects with Alzheimer disease without substantially altering its therapeutic index.

Asymmetries of brain glucose metabolism and memory in the healthy elderly

The relation of discrepancies between visual and verbal memory to right‐left asymmetries of resting state brain glucose metabolism was studied in 11 healthy elderly subjects. Short‐ and long‐term memory were measured with experimental continuous recognition tests. Regional cerebral metabolic rates for glucose were determined with positron emission tomography (PET) using 18F‐fluoro‐2‐deoxy‐D‐glucose. Long‐term memory discrepancy was related to parietal and hemispheric metabolic asymmetries, such that subjects with better visual than verbal memory had higher right than left brain glucose metabolic rates, whereas others showed the opposite pattern. These results show that specific visual and verbal memory abilities in the healthy elderly are related to regional differences in cerebral cortical metabolism.