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- Berginström, Nils, 1984-
(author)
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Fatigue after traumatic brain injury : exploring novel methods for diagnosis and treatment
- 2019
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 2. |
- Berginström, Nils, 1984-, et al.
(author)
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Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning
- 2017
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In: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 31:6-7, s. 755-755
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Journal article (peer-reviewed)abstract
- Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.
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| 3. |
- Berginström, Nils, 1984-, et al.
(author)
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Remote neuropsychological assessment of patients with neurological disorders and injuries : a study protocol for a cross-sectional case-control validation study
- 2024
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:4
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Journal article (peer-reviewed)abstract
- Introduction: There are great potential benefits of being able to conduct neuropsychological assessments remotely, especially for hard-to-reach or less mobile patient groups. Such tools need to be equivalent to standard tests done in the clinic and also easy to use in a variety of clinical populations.Methods and analysis: This study protocol describes a cross-sectional study aimed at validating the newly developed digitalized neuropsychological test battery Mindmore Remote in patients with neurological disorders and injuries. Diagnoses comprise traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis, brain tumour and epilepsy. 50 patients in each patient group will be included. In addition, 50 healthy controls will be recruited. All participants will undergo both testing with Mindmore Remote at home and traditional neuropsychological assessment face-to-face in a randomised order. The primary outcome is the association between tests from the Mindmore Remote battery and their equivalent traditional neuropsychological tests. Further, bias between methods and differences between groups will also be investigated.Ethics and dissemination: The study protocol has been approved by the Swedish Ethical Review Authority (2022-06230-01) and adheres to the declaration of Helsinki. All participants will be given oral and written information about the study and sign informed consent forms before entering the study. All participants are informed that they can terminate their participation in the study at any given time, without giving any explanation, and participating in the study or not will not affect their care at the clinic. Neither authors nor personnel involved in the research project are affiliated with Mindmore AB. The results from the study will be published in peer-reviewed scientific journals and presented at national and international conferences on the topic.Trial registration number: NCT05819008.
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| 4. |
- Berginström, Nils, 1984-, et al.
(author)
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White matter hyperintensities increases with traumatic brain injury severity : associations to neuropsychological performance and fatigue
- 2020
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In: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 34:3, s. 415-420
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Journal article (peer-reviewed)abstract
- Objective: To examine the prevalence of white matter hyperintensities (WMHs) in patients with traumatic brain injury (TBI) as compared to healthy controls, and to investigate whether there is an association between WMH lesion burden and performance on neuropsychological tests in patients with TBI.Methods: A total of 59 patients with TBI and 27 age- and gender-matched healthy controls underwent thorough neuropsychological testing and magnetic resonance imaging. The quantification of WMH lesions was performed using the fully automated Lesion Segmentation Tool.Results: WMH lesions were more common in patients with TBI than in healthy controls (p = .032), and increased with higher TBI severity (p = .025). Linear regressions showed that WMH lesions in patients with TBI were not related to performance on any neuropsychological tests (p > .05 for all). However, a negative relationship between number of WMH lesions in patients with TBI and self-assessed fatigue was found (r = - 0.33, p = .026).Conclusion: WMH lesions are more common in patients with TBI than in healthy controls, and WMH lesions burden increases with TBI severity. These lesions could not explain decreased cognitive functioning in patients with TBI but did relate to decreased self-assessment of fatigue after TBI.
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| 5. |
- Eriksson, Maija, et al.
(author)
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Sedentary behavior as a potential risk factor for depression among 70-year-olds
- 2020
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 263, s. 605-608
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Journal article (peer-reviewed)abstract
- Background: Sedentary behavior has previously been associated with the risk of depression. In addition, older adults have been proven to be more sedentary and more depressed than other age groups. However, studies using objective measures of sedentary behavior and taking physical activity into account are lacking. Thus, the purpose of this population-based study was to examine how total sedentary time and length of sedentary bouts were associated with the risk of depression among 70-year-olds.Methods: The present study used data from the Healthy Ageing Initiative (n = 3,633), an ongoing cross-sectional research project in Umeå, Sweden. Sedentary behavior was measured objectively with the ActiGraph GT3X+ accelerometer, and depression was measured with the Geriatric Depression Scale. Several covariates, including physical activity, were included in logistic regression analyses.Results: Results from two hierarchical logistic regression models showed that a greater percentage of the day spent sedentary [odds ratio (OR) = 1.031, p = 0.010] and longer average length of sedentary bouts (OR = 1.116, p = 0.045) increased the risk of depression.Limitations: Limitations include of possible underrepresentation of severely depressed participants, and possible observer effects.Conclusions: The present study verified the relationship between sedentary behavior and depression and provides new information about the risks associated with increased length of sedentary bouts. These findings may be important to consider in the development of future recommendations for the prevention of depression among older adults.
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| 6. |
- Holmqvist, Anna, et al.
(author)
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Fatigue and cognitive fatigability in patients with chronic pain
- 2024
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In: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 24:1
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Journal article (peer-reviewed)abstract
- Objectives: Fatigue is common in patients with chronic pain. Still, there is a lack of studies examining objectively measurable cognitive aspects of fatigue: cognitive fatigability (CF). We aimed to investigate the presence of CF in patients with chronic pain and its relation to self-rated fatigue, attention, pain characteristics, sleep disturbance, depression, and anxiety.Methods: Two hundred patients with chronic pain and a reference group of 36 healthy subjects underwent a comprehensive neuropsychological test battery, including measurement of CF with the Wechsler Adult Intelligence Scale-III Coding subtest, and self-assessment of trait and state fatigue.Results: The patients with chronic pain did not show more CF as compared to the reference group. There was an association between CF and processing speed on a test of sustained and selective attention in the chronic pain group, while self-rated fatigue measures and pain characteristics were not associated with CF. Self-rated fatigue measures were highly correlated with self-rated pain intensity, spreading of pain, depression, anxiety, and sleep disturbance.Conclusions: The findings highlight the distinction between objective and subjective aspects of fatigue in chronic pain, and that the underlying causes of these different aspects of fatigue need to be studied further.
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| 7. |
- Möller, Marika C., et al.
(author)
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Cognitive and mental fatigue in chronic pain : cognitive functions, emotional aspects, biomarkers and neuronal correlates - protocol for a descriptive cross-sectional study
- 2023
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In: BMJ Open. - : BMJ. - 2044-6055. ; 13:3
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Chronic pain (CP) is one of the most frequently presenting conditions in health care and many patients with CP report mental fatigue and a decline in cognitive functioning. However, the underlying mechanisms are still unknown.METHODS AND ANALYSIS: This study protocol describes a cross-sectional study aimed at investigating the presence of self-rated mental fatigue, objectively measured cognitive fatigability and executive functions and their relation to other cognitive functions, inflammatory biomarkers and brain connectivity in patients with CP. We will control for pain-related factors such as pain intensity and secondary factors such as sleep disturbances and psychological well-being. Two hundred patients 18-50 years with CP will be recruited for a neuropsychological investigation at two outpatient study centres in Sweden. The patients are compared with 36 healthy controls. Of these, 36 patients and 36 controls will undergo blood sampling for inflammatory markers, and of these, 24 female patients and 22 female controls, between 18 and 45 years, will undergo an functional MRI investigation. Primary outcomes are cognitive fatigability, executive inhibition, imaging and inflammatory markers. Secondary outcomes include self-rated fatigue, verbal fluency and working memory. The study provides an approach to study fatigue and cognitive functions in CP with objective measurements and may demonstrate new models of fatigue and cognition in CP.ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethics Review Board (Dnr 2018/424-31; 2018/1235-32; 2018/2395-32; 2019-66148; 2022-02838-02). All patients gave written informed consent to participate in the study. The study findings will be disseminated through publications in journals within the fields of pain, neuropsychology and rehabilitation. Results will be spread at relevant national and international conferences, meetings and expert forums. The results will be shared with user organisations and their members as well as relevant policymakers.TRIAL REGISTRATION NUMBER: NCT05452915.
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| 8. |
- Nyberg, Lars, 1966-, et al.
(author)
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Hjärnavbildningsmetoder i klinisk neuropsykologi
- 2023. - 3
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In: Klinisk neuropsykologi. - Lund : Studentlitteratur AB. - 9789144149066 ; , s. 237-249
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Book chapter (other academic/artistic)abstract
- Hjärnavbildningsmetoder är samlingsnamnet på ett stort antal tekniker som gör det möjligt att visualisera en levande persons hjärna. Teknikerna erbjuder alltså ett "fönster in i hjärnan" - en möjlighet som är hisnande men idag vardag både i forskning och i klinisk verksamhet. Under de senaste decennierna har olika tekniska landvinningar möjliggjort alltmer förfinade undersökningar, och denna utveckling fortsätter alltjämt. Verksamheter med inriktning på olika former av hjärnavbildning återfinns på sjukhus, universitet och forskningscentra. De ofta högteknologiska metoderna kräver att team av specialister, såsom inom neuroradiologi och fysiologi, samarbetar. På många platser är också neuropsykologer centrala medarbetare i dessa team, och det här kapitlet är riktat just mot (blivande) neuropsykologer med intresse för att nyttja hjärnavbildningsmetoder.
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