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Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: changes linked to altered Striato-Thalamic-Cortical Functioning
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
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2018 (English)In: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 33, no 4, p. 266-274Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI).

Setting: Neurorehabilitation clinic.

Participants: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27).

Main Measures: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task.

Results: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001).The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%.

Conclusion: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

Place, publisher, year, edition, pages
Wolters Kluwer, 2018. Vol. 33, no 4, p. 266-274
Keywords [en]
fatigue, functional magnetic resonance imaging, neuropsychology, traumatic brain injury
National Category
Neurology
Research subject
Rehabilitation Medicine
Identifiers
URN: urn:nbn:se:umu:diva-140021DOI: 10.1097/HTR.0000000000000340ISI: 000442745900013OAI: oai:DiVA.org:umu-140021DiVA, id: diva2:1145486
Funder
Västerbotten County CouncilTorsten Söderbergs stiftelseAvailable from: 2017-09-29 Created: 2017-09-29 Last updated: 2019-01-15Bibliographically approved
In thesis
1. Fatigue after traumatic brain injury: exploring novel methods for diagnosis and treatment
Open this publication in new window or tab >>Fatigue after traumatic brain injury: exploring novel methods for diagnosis and treatment
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Trötthet efter traumatisk skallskada : utforskande av nya metoder för diagnostik och behandling
Abstract [en]

Background: Traumatic brain injury (TBI) is one of the most common causes of disability and mortality. While some patients recover quickly, especially at the mild side of the injury severity continuum, many will experience symptoms for years to come. In this chronic phase, patients report a wide array of symptoms, where fatigue is one the most common. This fatigue makes huge impact in several areas of these patients’ lives. Despite the prevalence of fatigue after TBI, the underlying mechanisms are unclear. Further, there are no standardized way for assessment and diagnosis, and there are no treatments with satisfying empirical support. The aim of this thesis was to examine the effects of the novel compound OSU6162 on fatigue in patients with TBI, and to explore functional and structural brain imaging correlates of fatigue after TBI.

Methods: Studies I and III were based on a placebo-controlled, double-blinded clinical trial examining the effects of the monoaminergic stabilizer OSU6162 on fatigue in patients in the chronic phase of traumatic brain injury. In study I, self-assessment scales of fatigue and neuropsychological tests were used as outcomes, while functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) signal was the primary outcome in study III. Studies II and IV used cross-sectional designs, comparing patients with TBI with age- and gender matched healthy controls. Study II examined whether fMRI BOLD signal could be used to detect and diagnose fatigue in patients with TBI, and study IV whether white matter hyperintensities (WMH) contribute to lower cognitive functioning and presence of fatigue after TBI.

Results: Study I revealed no effects of OSU6162 during 28 days of treatment at maximum doses of 15 mg twice daily on measures of fatigue or any other outcome. The results from study II indicated that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and suggested that fMRI could be a promising technique to use in the diagnosis of fatigue after TBI. In study III the results revealed effects of treatment in the right occipitotemporal and orbitofrontal cortex. In these areas, the BOLD response was normalized in the OSU6162 group as compared to healthy controls, while the placebo group showed a steady low activity in these areas. The regional effects were located outside the network shown to be linked to fatigue in study II, which might explain why there were no effects on fatigue after treatment with OSU6162 in study I. Study IV showed that WMH lesions increased with increased TBI severity, but the presence and extent of lesions did not explain lower neuropsychological functioning or fatigue in subjects with previous TBI.

Conclusions: In summary, although no effects on fatigue after treatment with OSU6162 were seen, the results provide support to the theory that fatigue after TBI is linked to alterations in striato-thalamic-cortical loops, and on how fatigue after TBI could be assessed or diagnosed using fMRI. Structural damage within white matter was however not related to fatigue.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2019. p. 59
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2000
Keywords
Traumatic brain injury, fatigue, OSU6162, randomized clinical trials, functional magnetic resonance imaging, neuropsychology, structural magnetic resonance imaging, white matter hyperintensities
National Category
Other Medical Sciences not elsewhere specified
Research subject
Rehabilitation Medicine
Identifiers
urn:nbn:se:umu:diva-155409 (URN)978-91-7601-979-5 (ISBN)
Public defence
2019-02-08, Aulan, Vårdvetarhuset, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-01-18 Created: 2019-01-15 Last updated: 2019-01-17Bibliographically approved

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Berginström, NilsNordström, PeterEkman, UrbanEriksson, JohanAndersson, MicaelNyberg, LarsNordström, Anna

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