Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness

Overview

Journal Clin Psychol Sci

Publisher Sage Publications

Specialty Psychiatry

Date 2015 Mar 14

PMID 25767746

Citations 27

Authors

Nicholas A Hubbard

Joanna L Hutchison

Michael A Motes

Ehsan Shokri-Kojori

Ilana J Bennett

Ryan M Brigante

Robert W Haley

Bart Rypma

Affiliations

Soon will be listed here.

Abstract

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

Citing Articles

Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness.

Carpenter J, Hughes S, Filipov N Front Neurosci. 2024; 18:1465701.

PMID: 39308947 PMC: 11412963. DOI: 10.3389/fnins.2024.1465701.

Delayed cognitive impairments in a rat model of Gulf War Illness are stimulus-dependent.

Burzynski H, Ayala K, Frick M, Dufala H, Woodruff J, Macht V Brain Behav Immun. 2023; 113:248-258.

PMID: 37437820 PMC: 10530066. DOI: 10.1016/j.bbi.2023.07.003.

Ocular and inflammatory markers associated with Gulf War illness symptoms.

Kalahasty K, Lee Y, Locatelli E, Djulbegovic M, Cabrera K, Pakravan P Sci Rep. 2023; 13(1):3512.

PMID: 36864130 PMC: 9981620. DOI: 10.1038/s41598-023-30544-9.

Evaluation of delayed LNFPIII treatment initiation protocol on improving long-term behavioral and neuroinflammatory pathology in a mouse model of Gulf War Illness.

Carpenter J, Brown K, Veltmaat L, Ludwig H, Clay K, Norberg T Brain Behav Immun Health. 2022; 26:100553.

PMID: 36405424 PMC: 9668612. DOI: 10.1016/j.bbih.2022.100553.

Volunteer Foreign Fighters in the Ukrainian Conflict and Considerations for Forensic Psychiatry: Toward an Interdisciplinary Dialogue.

Smith A, Buadze A, Dube A, Schleifer R, Liebrenz M Front Psychiatry. 2022; 13:914369.

PMID: 35664472 PMC: 9161556. DOI: 10.3389/fpsyt.2022.914369.

References

Odegard T, Cooper C, Farris E, Arduengo J, Bartlett J, Haley R . Memory impairment exhibited by veterans with Gulf War Illness. Neurocase. 2012; 19(4):316-27. DOI: 10.1080/13554794.2012.667126. View

Gopinath K, Gandhi P, Goyal A, Jiang L, Fang Y, Ouyang L . FMRI reveals abnormal central processing of sensory and pain stimuli in ill Gulf War veterans. Neurotoxicology. 2012; 33(3):261-71. PMC: 3358633. DOI: 10.1016/j.neuro.2012.01.014. View

Haley R, Charuvastra E, Shell W, Buhner D, Marshall W, Biggs M . Cholinergic autonomic dysfunction in veterans with Gulf War illness: confirmation in a population-based sample. JAMA Neurol. 2013; 70(2):191-200. DOI: 10.1001/jamaneurol.2013.596. View

Tuite J, Haley R . Meteorological and intelligence evidence of long-distance transit of chemical weapons fallout from bombing early in the 1991 Persian Gulf War. Neuroepidemiology. 2012; 40(3):160-77. DOI: 10.1159/000345123. View

Salthouse T . The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996; 103(3):403-28. DOI: 10.1037/0033-295x.103.3.403. View

Haley R, Spence J, Carmack P, Gunst R, Schucany W, Petty F . Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War. Psychiatry Res. 2009; 171(3):207-20. DOI: 10.1016/j.pscychresns.2008.05.004. View

Rypma B, Berger J, DEsposito M . The influence of working-memory demand and subject performance on prefrontal cortical activity. J Cogn Neurosci. 2002; 14(5):721-31. DOI: 10.1162/08989290260138627. View

Hasselmo M . Neuromodulation and cortical function: modeling the physiological basis of behavior. Behav Brain Res. 1995; 67(1):1-27. DOI: 10.1016/0166-4328(94)00113-t. View

Hasselmo M, Giocomo L . Cholinergic modulation of cortical function. J Mol Neurosci. 2006; 30(1-2):133-5. DOI: 10.1385/JMN:30:1:133. View

10.

Haley R, Tuite J . Epidemiologic evidence of health effects from long-distance transit of chemical weapons fallout from bombing early in the 1991 Persian Gulf War. Neuroepidemiology. 2012; 40(3):178-89. DOI: 10.1159/000345124. View

11.

Ragozzino M, Artis S, Singh A, Twose T, Beck J, Messer Jr W . The selective M1 muscarinic cholinergic agonist CDD-0102A enhances working memory and cognitive flexibility. J Pharmacol Exp Ther. 2011; 340(3):588-94. PMC: 3286311. DOI: 10.1124/jpet.111.187625. View

12.

Hasselmo M, McGaughy J . High acetylcholine levels set circuit dynamics for attention and encoding and low acetylcholine levels set dynamics for consolidation. Prog Brain Res. 2003; 145:207-31. DOI: 10.1016/S0079-6123(03)45015-2. View

13.

Bartus R . On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol. 2000; 163(2):495-529. DOI: 10.1006/exnr.2000.7397. View

14.

Dumas J, Saykin A, McDonald B, McAllister T, Hynes M, Newhouse P . Nicotinic versus muscarinic blockade alters verbal working memory-related brain activity in older women. Am J Geriatr Psychiatry. 2008; 16(4):272-82. PMC: 3114443. DOI: 10.1097/JGP.0b013e3181602a2b. View

15.

Voss B, Thienel R, Reske M, Kellermann T, Sheldrick A, Halfter S . Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects. Eur Arch Psychiatry Clin Neurosci. 2011; 262(4):329-39. DOI: 10.1007/s00406-011-0267-6. View

16.

Cowan N . The magical number 4 in short-term memory: a reconsideration of mental storage capacity. Behav Brain Sci. 2001; 24(1):87-114; discussion 114-85. DOI: 10.1017/s0140525x01003922. View

17.

Rypma B, DEsposito M . The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences. Proc Natl Acad Sci U S A. 1999; 96(11):6558-63. PMC: 26921. DOI: 10.1073/pnas.96.11.6558. View

18.

Rusted J . Dissociative effects of scopolamine on working memory in healthy young volunteers. Psychopharmacology (Berl). 1988; 96(4):487-92. DOI: 10.1007/BF02180029. View

19.

Rypma B, Prabhakaran V, Desmond J, Glover G, Gabrieli J . Load-dependent roles of frontal brain regions in the maintenance of working memory. Neuroimage. 1999; 9(2):216-26. DOI: 10.1006/nimg.1998.0404. View

20.

Rusted J, Warburton D . The effects of scopolamine on working memory in healthy young volunteers. Psychopharmacology (Berl). 1988; 96(2):145-52. DOI: 10.1007/BF00177553. View