A Double FDG/PET Study of the Effects of Scopolamine in Older Adults

Molchan, Susan E.; Matochik, John A.; Zametkin, Alan J.; Szymanski, Herman V.; Cantillon, Marc; Cohen, Robert M.; Sunderland, Trey

doi:10.1038/npp.1994.21

Cited by 25 publications

(13 citation statements)

References 28 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significance values are based on a linear mixed-effects model, and are corrected for multiple comparisons: ‫,ء‬ P Ͻ 0.05; †, P Ͻ 0.01; §, P Ͻ 0.0001. ciated with pharmacologic manipulation. These studies, primarily using PET techniques, have examined the effects of scopolamine or benzodiazepines on baseline metabolism (18,20,32) and͞or on task-related activation (19)(20)(21)33). Grasby et al (20) studied the effects of scopolamine by using PET during a supraspan verbal memory task and found a decrease in taskrelated PET activation in the right anterior cingulate and bilateral prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

“…Both benzodiazepines and scopolamine have been shown to selectively impair the ability to encode new information, with relative sparing of semantic and procedural memory (13,16,17). Less is known regarding the regional specificity of these medication effects on functional brain activity, although recently, several studies have used functional imaging to examine effects of lorazepam or scopolamine on memory-related activation (18)(19)(20)(21). The majority of these studies have used positron-emission tomography (PET) imaging techniques (18)(19)(20), with the exception of one recent fMRI study, which examined the effects of these medications on priming (21).…”

mentioning

confidence: 99%

“…Less is known regarding the regional specificity of these medication effects on functional brain activity, although recently, several studies have used functional imaging to examine effects of lorazepam or scopolamine on memory-related activation (18)(19)(20)(21). The majority of these studies have used positron-emission tomography (PET) imaging techniques (18)(19)(20), with the exception of one recent fMRI study, which examined the effects of these medications on priming (21). These previous studies did not, however, employ cognitive tasks that produced significant activation within the hippocampus and, thus, could not examine alterations in hippocampal activity with drug administration.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Functional MRI detection of pharmacologically induced memory impairment

Sperling

Greve²,

Dale³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

191

147

View full text Add to dashboard Cite

To examine alterations in brain activation associated with pharmacologically induced memory impairment, we used functional MRI (fMRI) to study the effects of lorazepam and scopolamine on a face–name associative encoding paradigm. Ten healthy young subjects were scanned on four occasions, 2 weeks apart; they were administered i.v. saline during two placebo-scanning sessions and then alternately administered i.v. lorazepam (1 mg) or scopolamine (0.4 mg) in a double-blind, randomized, cross-over design. Both the extent and magnitude of activation within anatomic regions of interest (ROIs) were examined to determine the reproducibility of activation in the placebo sessions and the regional specificity of the pharmacologic effects. Activation within all ROIs was consistent across the two placebo scans during the encoding of novel face–name pairs (compared with visual fixation). With the administration of either lorazepam or scopolamine, significant decreases were observed in both the extent and magnitude of activation within the hippocampal, fusiform, and inferior prefrontal ROIs, but no significant alterations in activation in the striate cortex were found. Both medications impaired performance on postscan memory measures, and significant correlations between memory performance and extent of activation were found in hippocampal and fusiform ROIs. These findings suggest that pharmacologic effects can be detected with fMRI by using a reproducible experimental paradigm and that medications that impair memory also diminish activation in specific brain regions thought to subserve complex memory processes.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Functional MRI detection of pharmacologically induced memory impairment

Sperling

Greve²,

Dale³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

191

147

View full text Add to dashboard Cite

show abstract

“…We think that the deterioration in the cholinergic system may explain some, but not all of the deficits encountered in Alzheimer's disease. In our previous FDG/PET study in elderly normal adults treated with scopolamine [46], we were also unable to obtain data consistent with the typical images seen in Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 84%

“…In our experiment we used a dose of scopolamine about 50 times lower than that used in the study of Ogawa et al [45]. Moreover, in a previous human imaging study using scopolamine, Molchan et al [46] found that rCBF and regional glucose metabolism were extremely localized and did not show the generalized pattern one might expect from a vasoconstrictive response. Rather, in agreement with numerous studies on humans using similar doses, we think that the effects of scopolamine result in direct neuronal blockade of muscarinic stimulation.…”

Section: Discussionmentioning

confidence: 96%

The Effects of Scopolamine on Changes in Regional Cerebral Blood Flow during Classical Conditioning of the Human Eyeblink Response

Bahro

Molchan²,

Sunderland³

et al. 1999

Neuropsychobiology

Self Cite

View full text Add to dashboard Cite

We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age ± SEM: 26.7 ± 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H₂¹⁵O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 ± 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system.

show abstract

Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks

Kikuchi

Nasir

Inami

et al. 2018

Human Psychopharmacology

View full text Add to dashboard Cite

ObjectiveAntihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.MethodsIn this double‐blind, placebo‐controlled, three‐way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two‐back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near‐infrared spectroscopy.ResultsEnergy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.ConclusionsPhysiological “coupling” between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

show abstract

A Double FDG/PET Study of the Effects of Scopolamine in Older Adults

Cited by 25 publications

References 28 publications

Functional MRI detection of pharmacologically induced memory impairment

Functional MRI detection of pharmacologically induced memory impairment

The Effects of Scopolamine on Changes in Regional Cerebral Blood Flow during Classical Conditioning of the Human Eyeblink Response

Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks

Contact Info

Product

Resources

About