Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance

Marika C Möller, Love Engström Nordin, Aniko Bartfai, Per Julin, Tie-Qiang Li, Marika C Möller, Love Engström Nordin, Aniko Bartfai, Per Julin, Tie-Qiang Li

Abstract

Introduction: Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI.

Material and methods: Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT.

Results: The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period.

Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.

Keywords: cerebral blood flow; fatigue; functional magnetic resonance imaging; mild traumatic brain injury; pseudo-continuous arterial spin labeling.

Figures

Figure 1
Figure 1
Boxplots of Visual Analog Scale of Fatigue (VAS-f) ratings before and after psychomotor vigilance task (PVT) for patients and controls, respectively. The mild traumatic brain injury patients reported significantly more self-rated current fatigue (VAS-f) than the healthy controls after the PVT (p < 0.01) according to Mann–Whitney U test.
Figure 2
Figure 2
The mean reaction time (RTmean) in each quintile during the psychomotor vigilance task (PVT) performance for the mild traumatic brain injury patients and healthy control subjects. The error bars show the SD of RT (RTstd) per quintile.
Figure 3
Figure 3
The RTRSD in the last quintile of psychomotor vigilance task (PVT) performance vs. the self-rated fatigue immediate after the PVT performance. The line indicates the linear least square fitting to the measured data points (r = 0.48, p = 0.03).
Figure 4
Figure 4
Summary of the F-score results from the three-way ANOVA modeling of the regional cerebral blood flow data acquired during a 20-min psychomotor vigilance task (PVT) performance to illustrate the brain regions of statistically significant differences (family-wise error rate, p ≤ 0.05) in neural activity associated with the two fixed factors (the PVT performance time and subject group) and their interaction. (A) The effect of PVT performance time; (B) the interaction effect between the PVT performance time and subject groups. The color bar indicates the F-score of the three-way ANOVA results.
Figure 5
Figure 5
Summary of brain regions with a significant correlation (family-wise error rate, p < 0.05) between regional cerebral blood flow and the Visual Analog Scale of Fatigue ratings after MRI for mild traumatic brain injury patients (n = 10) in each quintile of the psychomotor vigilance task performance. The color bar indicates the results from the different quintiles and their overlaps.

References

    1. Lannsjo M, af Geijerstam JL, Johansson U, Bring J, Borg J. Prevalence and structure of symptoms at 3 months after mild traumatic brain injury in a national cohort. Brain Inj (2009) 23(3):213–9.10.1080/02699050902748356
    1. Stulemeijer M, van der Werf S, Bleijenberg G, Biert J, Brauer J, Vos PE. Recovery from mild traumatic brain injury: a focus on fatigue. J Neurol (2006) 253(8):1041–7.10.1007/s00415-006-0156-5
    1. Ouellet M-C, Morin CM. Fatigue following traumatic brain injury: frequency, characteristics, and associated factors. Rehabil Psychol (2006) 51(2):140–9.10.1037/0090-5550.51.2.140
    1. Waljas M, Iverson GL, Lange RT, Liimatainen S, Hartikainen KM, Dastidar P, et al. Return to work following mild traumatic brain injury. J Head Trauma Rehabil (2014) 29(5):443–50.10.1097/HTR.0000000000000002
    1. Ashman TA, Cantor JB, Gordon WA, Spielman L, Egan M, Ginsberg A, et al. Objective measurement of fatigue following traumatic brain injury. J Head Trauma Rehabil (2008) 23(1):33–40.10.1097/01.HTR.0000308719.70288.22
    1. Zwarts MJ, Bleijenberg G, van Engelen BGM. Clinical neurophysiology of fatigue. Clin Neurophysiol (2008) 119:2–10.10.1016/j.clinph.2007.09.126
    1. DeLuca J. Fatigue: its definition, its study, and its future. In: DeLuca J, editor. Fatigue as a Window to the Brain. Cambridge: MIT Press; (2005). p. 319–25.
    1. Ackerman PL. Introduction. In: Ackerman PL, editor. Cognitive Fatigue Multidisciplinary Perspectives on Current Research and Future Applications. Washington, DC: American Psychological Association; (2010). p. 3–7.
    1. Schwid SR, Covington M, Segal BM, Goodman AD. Fatigue in multiple sclerosis: current understanding and future directions. J Rehabil Res Dev (2002) 39(2):211–24.
    1. Davis MP, Walsh D. Mechanisms of fatigue. J Support Oncol (2010) 8(4):164–74.
    1. Kluger BM, Krupp LB, Enoka RM. Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology (2013) 80(4):409–16.10.1212/WNL.0b013e31827f07be
    1. Schwid SR, Tyler CM, Scheid EA, Weinstein A, Goodman AD, McDermott MP. Cognitive fatigue during a test requiring sustained attention: a pilot study. Mult Scler (2003) 9(5):503–8.10.1191/1352458503ms946oa
    1. Bryant D, Chiaravalloti ND, DeLuca J. Objective measurement of cognitive fatigue in multiple sclerosis. Rehabil Psychol (2004) 49(2):114–22.10.1037/0090-5550.49.2.114
    1. Ackerman PL. 100 years without resting. In: Ackerman PL, editor. Cognitive Fatigue Multidisciplinary Perspectives on Current Research and Future Applications. Washington, DC: American Psychological Association; (2010). p. 11–43.
    1. Boksem MAS, Meijman TF, Lorist MM. Effects of mental fatigue on attention: an ERP study. Brain Res Cogn Brain Res (2005) 25(1):107–16.10.1016/j.cogbrainres.2005.04.011
    1. Möller MC, Nygren de Boussard C, Oldenburg C, Bartfai A. An investigation of attention, executive, and psychomotor aspects of cognitive fatigability. J Clin Exp Neuropsychol (2014) 26:1–14.10.1080/13803395.2014.933779
    1. Nordin LE, Moller MC, Julin P, Bartfai A, Hashim F, Li TQ. Post mTBI fatigue is associated with abnormal brain functional connectivity. Sci Rep (2016) 6:21183.10.1038/srep21183
    1. Xie L, Dolui S, Das SR, Stockbower GE, Daffner M, Rao H, et al. A brain stress test: cerebral perfusion during memory encoding in mild cognitive impairment. Neuroimage Clin (2016) 11:388–97.10.1016/j.nicl.2016.03.002
    1. Lim J, Wen-chau W, Jiongjiong W, Detre JA, Dinges DF, Rao H. Imaging brain fatigue from sustained mental workload: an AS perfusion study of the time-on-task effect. Neuroimage (2010) 49:3426–35.10.1016/j.neuroimage.2009.11.020
    1. Aguirre GK, Detre JA, Zarahn E, Alsop DC. Experimental design and the relative sensitivity of BOLD and perfusion fMRI. Neuroimage (2002) 15(3):488–500.10.1006/nimg.2001.0990
    1. Wang J, Aguirre GK, Kimberg DY, Roc AC, Li L, Detre JA. Arterial spin labeling perfusion fMRI with very low task frequency. Magn Reson Med (2003) 49(5):796–802.10.1002/mrm.10437
    1. Kim J, Whyte J, Wang J, Rao H, Tang KZ, Detre JA. Continuous ASL perfusion fMRI investigation of higher cognition: quantification of tonic CBF changes during sustained attention and working memory tasks. Neuroimage (2006) 31(1):376–85.10.1016/j.neuroimage.2005.11.035
    1. Mild traumatic brain injury committee of the head injury interdisciplinary special interest group of the American Congress of Rehabilitation Medicine: definition of mild traumatic brain injury. J Head Trauma Rehabil (1993) 8(3):86–7.10.1097/00001199-199309000-00010
    1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol (1989) 46(10):1121–3.10.1001/archneur.1989.00520460115022
    1. Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue. A practical guide for clinicians and researchers. J Psychosom Res (2004) 56:157–70.10.1016/S0022-3999(03)00371-4
    1. Buysse DJ, Reynolds CF, III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res (1989) 28(2):193–213.10.1016/0165-1781(89)90047-4
    1. Wang Z, Aguirre GK, Rao H, Wang J, Fernández-Seara MA, Childress AR, et al. Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. Magn Reson Imaging (2008) 26(2):261–9.10.1016/j.mri.2007.07.003
    1. Pellicano C, Gallo A, Li X, Ikonomidou VN, Evangelou IE, Ohayon JM, et al. Relationship of cortical atrophy to fatigue in patients with multiple sclerosis. Arch Neurol (2010) 67(4):447–53.10.1001/archneurol.2010.48
    1. Kohl AD, Wylie GR, Genova HM, Hillary FG, Deluca J. The neural correlates of cognitive fatigue in traumatic brain injury using functional MRI. Brain Inj (2009) 23(5):420–32.10.1080/02699050902788519
    1. Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W, et al. Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: an 18F-fluorodeoxyglucose positron emission tomography study. Neurology (1997) 48(6):1566–71.10.1212/WNL.48.6.1566
    1. Boksem MAS, Tops M. Mental fatigue: costs and benefits. Brain Res Rev (2008) 59(1):125–39.10.1016/j.brainresrev.2008.07.001
    1. Chaudhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci (2000) 179(S 1–2):34–42.10.1016/S0022-510X(00)00411-1
    1. Shallice T, Stuss DT, Alexander MP, Picton TW, Derkzen D. The multiple dimensions of sustained attention. Cortex (2008) 44(7):794–805.10.1016/j.cortex.2007.04.002
    1. Stalnacke BM. Postconcussion symptoms in patients with injury-related chronic pain. Rehabil Res Pract Print (2012) 2012:528265.10.1155/2012/528265
    1. Stuss DT. Functions of the frontal lobes: relation to executive functions. J Int Neuropsychol Soc (2011) 17:759–65.10.1017/S1355617711000695
    1. Lorist MM, Boksem MAS, Ridderinkhof KR. Impaired cognitive control and reduced cingulate activity during mental fatigue. Brain Res Cogn Brain Res (2005) 24(2):199–205.10.1016/j.cogbrainres.2005.01.018
    1. Dobryakova E, Deluca J, Genova HM, Wylie GR. Neural correlates of cognitive fatigue: cortico-striatal circuitry and effort-reward imbalance. J Int Neuropsychol Soc (2013) 19(8):849–53.10.1017/S1355617713000684
    1. Leavitt VM, DeLuca J. Central fatigue: issues related to cognition, mood and behavior, and psychiatric diagnoses. PM R (2010) 2(5):332–7.10.1016/j.pmrj.2010.03.027
    1. Vellucci R. Heterogeneity of chronic pain. Clin Drug Investig (2012) 32(Suppl 1):3–10.10.2165/11630030-000000000-00000
    1. Lim J, Dinges DF. Sleep deprivation and vigilant attention. Ann N Y Acad Sci (2008) 1129:305–22.10.1196/annals.1417.002
    1. Kaufmann T, Elvsashagen T, Alnaes D, Zak N, Pedersen PO, Norbom LB, et al. The brain functional connectome is robustly altered by lack of sleep. Neuroimage (2016) 127:324–32.10.1016/j.neuroimage.2015.12.028
    1. Depue BE, Burgess GC, Bidwell LC, Willcutt EG, Banich MT. Behavioral performance predicts gray matter reductions in the right inferior frontal gyrus in young adults with combined-type ADHD. Psychiatry Res (2010) 182(3):231–7.10.1016/j.pscychresns.2010.01.012
    1. Hampshire A, Chamberlain SR, Monti MM, Duncan J, Owen AM. The role of the right inferior frontal gyrus: inhibition and attentional control. Neuroimage (2010) 50(3):1313–9.10.1016/j.neuroimage.2009.12.109
    1. Shigihara Y, Tanaka M, Ishii A, Kanai E, Funakura M, Watanabe Y. Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways. Behav Brain Funct (2013) 9:2.10.1186/1744-9081-9-2
    1. Heitger MH, Jones RD, Macleod AD, Snell DL, Frampton CM, Anderson TJ. Impaired eye movements in post-concussion syndrome indicate suboptimal brain function beyond the influence of depression, malingering or intellectual ability. Brain (2009) 132(Pt 10):2850–70.10.1093/brain/awp181
    1. Alahmadi AA, Pardini M, Samson RS, D’Angelo E, Friston KJ, Toosy AT, et al. Differential involvement of cortical and cerebellar areas using dominant and nondominant hands: an fMRI study. Hum Brain Mapp (2015) 36(12):5079–100.10.1002/hbm.22997
    1. Seitz RJ, Roland PE. Learning of sequential finger movements in man: a combined kinematic and positron emission tomography (PET) study. Eur J Neurosci (1992) 4(2):154–65.10.1111/j.1460-9568.1992.tb00862.x
    1. Boissoneault J, Letzen J, Lai S, O’Shea A, Craggs J, Robinson ME, et al. Abnormal resting-state functional connectivity in patients with chronic fatigue syndrome: an arterial spin labeling fMRI study. Magn Reson Imaging (2016) 34(4):603–8.10.1016/j.mri.2015.12.008
    1. Aslan S, Lu H. On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow. Magn Reson Imaging (2010) 28(7):928–35.10.1016/j.mri.2010.03.037
    1. Drummond SP, Bischoff-Grethe A, Dinges DF, Ayalon L, Mednick SC, Meloy MJ. The neural basis of the psychomotor vigilance task. Sleep (2005) 28(9):1059–68.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel