Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory

M. L. Furey, P. Pietrini, J. V. Haxby, Gene E Alexander, H. C. Lee, J. Vanmeter, C. L. Grady, U. Shetty, S. I. Rapoport, M. B. Schapiro, U. Freo

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

Original languageEnglish (US)
Pages (from-to)6512-6516
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number12
DOIs
StatePublished - Jun 10 1997
Externally publishedYes

Fingerprint

Cerebrovascular Circulation
Regional Blood Flow
Task Performance and Analysis
Short-Term Memory
Cholinergic Agents
Physostigmine
Positron-Emission Tomography
Reaction Time
Efficiency
Cholinesterase Inhibitors
Prefrontal Cortex
Neurotransmitter Agents
Healthy Volunteers
Alzheimer Disease

Keywords

  • Acetylcholine
  • Physostigmine
  • Positron emission tomography
  • Prefrontal cortex

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. / Furey, M. L.; Pietrini, P.; Haxby, J. V.; Alexander, Gene E; Lee, H. C.; Vanmeter, J.; Grady, C. L.; Shetty, U.; Rapoport, S. I.; Schapiro, M. B.; Freo, U.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 12, 10.06.1997, p. 6512-6516.

Research output: Contribution to journalArticle

Furey, M. L. ; Pietrini, P. ; Haxby, J. V. ; Alexander, Gene E ; Lee, H. C. ; Vanmeter, J. ; Grady, C. L. ; Shetty, U. ; Rapoport, S. I. ; Schapiro, M. B. ; Freo, U. / Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 12. pp. 6512-6516.
@article{7cbcac7b5e024715ac06235f1229f367,
title = "Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory",
abstract = "Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.",
keywords = "Acetylcholine, Physostigmine, Positron emission tomography, Prefrontal cortex",
author = "Furey, {M. L.} and P. Pietrini and Haxby, {J. V.} and Alexander, {Gene E} and Lee, {H. C.} and J. Vanmeter and Grady, {C. L.} and U. Shetty and Rapoport, {S. I.} and Schapiro, {M. B.} and U. Freo",
year = "1997",
month = "6",
day = "10",
doi = "10.1073/pnas.94.12.6512",
language = "English (US)",
volume = "94",
pages = "6512--6516",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "12",

}

TY - JOUR

T1 - Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory

AU - Furey, M. L.

AU - Pietrini, P.

AU - Haxby, J. V.

AU - Alexander, Gene E

AU - Lee, H. C.

AU - Vanmeter, J.

AU - Grady, C. L.

AU - Shetty, U.

AU - Rapoport, S. I.

AU - Schapiro, M. B.

AU - Freo, U.

PY - 1997/6/10

Y1 - 1997/6/10

N2 - Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

AB - Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

KW - Acetylcholine

KW - Physostigmine

KW - Positron emission tomography

KW - Prefrontal cortex

UR - http://www.scopus.com/inward/record.url?scp=12644317816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12644317816&partnerID=8YFLogxK

U2 - 10.1073/pnas.94.12.6512

DO - 10.1073/pnas.94.12.6512

M3 - Article

C2 - 9177249

AN - SCOPUS:12644317816

VL - 94

SP - 6512

EP - 6516

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 12

ER -