Alpha-2 adrenergic challenge with guanfacine one month after mild traumatic brain injury: Altered working memory and BOLD response
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Alterations in working memory (WM) are common after traumatic brain injury (TBI). Frontal catecholaminergic systems, including the alpha-2 adrenergic system, modulate WM function and may be affected in TBI. We hypothesized that administration of an alpha-2 adrenergic agonist might improve WM after mild TBI (MTBI). Thirteen individuals with MTBI 1month after injury and 14 healthy controls (HC) were challenged with guanfacine and placebo prior to administration of a verbal WM functional MRI task. Guanfacine was associated with improved WM performance in the MTBI but not the HC group. On guanfacine the MTBI group showed increased activation within a WM task-specific region of interest. Findings are consistent with the hypothesis that alterations in WM after MTBI may be improved with the alpha-2 agonist guanfacine.
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Studies of humans with TBI support the view that guanfacine improves working memory and enhances fMRI BOLD activation of PFC.
“Studies of humans with TBI support this view (McAllister et al., 2004, McAllister et al., 2011), including evidence of improved working memory and enhanced fMRI BOLD activation of PFC (McAllister et al., 2011).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as McAllister et al., 2011
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- Authors
- McAllister, T. W., McDonald, B. C., Flashman, L. A., Ferrell, R. B., Tosteson, T. D., Yanofsky, N. N., Grove, M. R., & Saykin, A. J.
- Affiliations
- Dartmouth College (US)
- Indiana University Indianapolis (US)
- Dartmouth–Hitchcock Medical Center (US)
- Corresponding author
- McAllister, Thomas W.
- Venue
- International Journal of Psychophysiology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 82
- Issue
- 1
- Pages
- 107-114
- ISSN
- 0167-8760 (ISSN-L)
- PMC
- PMC3210922
- OpenAlex
- W2050629291
- Cited by
- 70
- References
- 56
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 5
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Psychophysiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- Dartmouth College
- National Institutes of Health
- National Institute on Disability and Rehabilitation Research
- National Cancer Institute (P30CA023108)
- National Institute of Neurological Disorders and Stroke (R01-NS-40472-01, R01NS040472)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Keywords
- mild traumatic brain injury, working memory, alpha-2 adrenergic agonists, guanfacine, BOLD signal, catecholaminergic system, frontal cortex, functional MRI, pharmacological challenge
- MeSH terms
- Adult, Brain, Brain Injuries, Brain Mapping, Cognition Disorders, Double-Blind Method, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory Disorders, Memory, Short-Term, Neuropsychological Tests, Oxygen, Prospective Studies, Trauma Severity Indices, Guanfacine, Young Adult, Adrenergic alpha-2 Receptor Agonists
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