Abstract
Fatigue is defined as a decline in the ability and efficiency of mental and/or physical activities that is caused by excessive mental and/or physical activities. Fatigue can be classified as physical or mental. Mental fatigue manifests as potentially impaired cognitive function and is one of the most significant causes of accidents in modern society. Recently, it has been shown that the neural mechanisms of mental fatigue related to cognitive task performance are more complex than previously thought and that mental fatigue is not caused only by impaired activity in task-related brain regions. There is accumulating evidence supporting the existence of mental facilitation and inhibition systems. These systems are involved in the neural mechanisms of mental fatigue, modulating the activity of task-related brain regions to regulate cognitive task performance. In this review, we propose a new conceptual model: the dual regulation system of mental fatigue. This model contributes to our understanding of the neural mechanisms of mental fatigue and the regulatory mechanisms of cognitive task performance in the presence of mental fatigue.
About the authors

Akira Ishii is an Assistant Professor, Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan. He is also a medical doctor. In 2010, he took a medical doctorate (PhD) at Osaka City University Graduate School of Medicine. His specialty is Fatigue Science and Functional Neuroimaging.

Masaaki Tanaka is an Assistant Professor, Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan. He is also a medical doctor. In 2003, he took a medical doctorate (PhD) at Osaka City University Graduate School of Medicine. His specialty is Fatigue Science and Functional Neuroimaging.

Yasuyoshi Watanabe is a Director, Center for Life Science Technologies, RIKEN and a Professor, Department of Physiology, Osaka City University Graduate School of Medicine. He is also a medical doctor. In 1981, he took a medical doctorate (PhD) at Kyoto University. His specialty is Fatigue Science and Molecular Neuroimaging.
Acknowledgments
This work was supported, in part, by a Grant-in-Aid for Scientific Research B (KAKENHI: 23300241) and a Grant-in-Aid for Young Scientists (B) (KAKENHI: 23700804, 25750351) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan and by grants from the Japanese Ministry of Health, Labor, and Welfare. We thank Forte Science Communication for editorial help with the manuscript.
References
Akselrod, S., Gordon, D., Ubel, F.A., Shannon, D.C., Berger, A.C., and Cohen, R.J. (1981). Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213, 220–222.10.1126/science.6166045Search in Google Scholar
Appel, M.L., Berger, R.D., Saul, J.P., Smith, J.M., and Cohen, R.J. (1989). Beat to beat variability in cardiovascular variables: noise or music? J. Am. Coll. Cardiol. 14, 1139–1148.10.1016/0735-1097(89)90408-7Search in Google Scholar
Baker, S.N., Olivier, E., and Lemon, R.N. (1997). Coherent oscillations in monkey motor cortex and hand muscle EMG show task-dependent modulation. J. Physiol. 501, 225–241.10.1111/j.1469-7793.1997.225bo.xSearch in Google Scholar
Boksem, M.A. and Tops, M. (2008). Mental fatigue: costs and benefits. Brain Res. Rev. 59, 125–139.10.1016/j.brainresrev.2008.07.001Search in Google Scholar
Boksem, M.A., Meijman, T.F., and Lorist, M.M. (2005). Effects of mental fatigue on attention: an ERP study. Brain Res. Cogn. Brain Res. 25, 107–116.10.1016/j.cogbrainres.2005.04.011Search in Google Scholar
Boksem, M.A., Meijman, T.F., and Lorist, M.M. (2006). Mental fatigue, motivation and action monitoring. Biol. Psychol. 72, 123–132.10.1016/j.biopsycho.2005.08.007Search in Google Scholar
Brookes, M.J., Wood, J.R., Stevenson, C.M., Zumer, J.M., White, T.P., Liddle, P.F., and Morris, P.G. (2011). Changes in brain network activity during working memory tasks: a magnetoencephalography study. Neuroimage 55, 1804–1815.10.1016/j.neuroimage.2010.10.074Search in Google Scholar
Carter, C.S. and van Veen, V. (2007). Anterior cingulate cortex and conflict detection: an update of theory and data. Cogn. Affect. Behav. Neurosci. 7, 367–379.10.3758/CABN.7.4.367Search in Google Scholar
Caseras, X., Mataix-Cols, D., Giampietro, V., Rimes, K.A., Brammer, M., Zelaya, F., Chalder, T., and Godfrey, E.L. (2006). Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom. Med. 68, 947–955.10.1097/01.psy.0000242770.50979.5fSearch in Google Scholar
Chaudhuri, A. and Behan, P.O. (2000). Fatigue and basal ganglia. J. Neurol. Sci. 179, 34–42.10.1016/S0022-510X(00)00411-1Search in Google Scholar
Chaudhuri, A. and Behan, P.O. (2004). Fatigue in neurological disorders. Lancet 363, 978–988.10.1016/S0140-6736(04)15794-2Search in Google Scholar
Cleare, A.J., Messa, C., Rabiner, E.A., and Grasby, P.M. (2005). Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol. Psychiatry 57, 239–246.10.1016/j.biopsych.2004.10.031Search in Google Scholar PubMed
Cook, D.B., O’Connor, P.J., Lange, G., and Steffener, J. (2007). Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage 36, 108–122.10.1016/j.neuroimage.2007.02.033Search in Google Scholar PubMed
Craig, A.D. (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3, 655–666.10.1038/nrn894Search in Google Scholar PubMed
Craig, A.D. (2009). Emotional moments across time: a possible neural basis for time perception in the anterior insula. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 1933–1942.10.1098/rstb.2009.0008Search in Google Scholar PubMed PubMed Central
de Lange, F.P., Kalkman, J.S., Bleijenberg, G., Hagoort, P., van der Werf, S.P., van der Meer, J.W., and Toni, I. (2004). Neural correlates of the chronic fatigue syndrome – an fMRI study. Brain 127, 1948–1957.10.1093/brain/awh225Search in Google Scholar PubMed
de Lange, F.P., Koers, A., Kalkman, J.S., Bleijenberg, G., Hagoort, P., van der Meer, J.W., and Toni, I. (2008). Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain 131, 2172–2180.10.1093/brain/awn140Search in Google Scholar PubMed
Decorde, K., Ventura, E., Lacan, D., Ramos, J., Cristol, J.P., and Rouanet, J.M. (2010). An SOD rich melon extract Extramel prevents aortic lipids and liver steatosis in diet-induced model of atherosclerosis. Nutr. Metab. Cardiovasc. Dis. 20, 301–307.10.1016/j.numecd.2009.04.017Search in Google Scholar PubMed
DeLuca, J., Genova, H.M., Hillary, F.G., and Wylie, G. (2008). Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. J. Neurol. Sci. 270, 28–39.10.1016/j.jns.2008.01.018Search in Google Scholar PubMed
Denton, D., Shade, R., Zamarippa, F., Egan, G., Blair-West, J., McKinley, M., Lancaster, J., and Fox, P. (1999). Neuroimaging of genesis and satiation of thirst and an interoceptor-driven theory of origins of primary consciousness. Proc. Natl. Acad. Sci. USA 96, 5304–5309.10.1073/pnas.96.9.5304Search in Google Scholar PubMed PubMed Central
Desmond, P. and Hancock, P. (2001). Active and passive fatigue states. In Stress, Workload, and Fatigue. P. Hancock and P. Desmond, eds. (Lawrence Erlbaum Associates, Mahwah, NJ), pp. 455–462.Search in Google Scholar
Dettmers, C., Lemon, R.N., Stephan, K.M., Fink, G.R., and Frackowiak, R.S. (1996). Cerebral activation during the exertion of sustained static force in man. Neuroreport 7, 2103–2110.10.1097/00001756-199609020-00008Search in Google Scholar PubMed
Dobryakova, E., DeLuca, J., Genova, H.M., and Wylie, G.R. (2013). Neural correlates of cognitive fatigue: cortico-striatal circuitry and effort-reward imbalance. J. Int. Neuropsychol. Soc. 19, 849–853.10.1017/S1355617713000684Search in Google Scholar PubMed
Dorrian, J., Roach, G.D., Fletcher, A., and Dawson, D. (2007). Simulated train driving: fatigue, self-awareness and cognitive disengagement. Appl. Ergon. 38, 155–166.10.1016/j.apergo.2006.03.006Search in Google Scholar PubMed
Filippi, M., Rocca, M.A., Colombo, B., Falini, A., Codella, M., Scotti, G., and Comi, G. (2002). Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage 15, 559–567.10.1006/nimg.2001.1011Search in Google Scholar PubMed
Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., and Komaroff, A. (1994). The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann. Intern. Med. 121, 953–959.10.7326/0003-4819-121-12-199412150-00009Search in Google Scholar PubMed
Gandevia, S.C., Allen, G.M., Butler, J.E., and Taylor, J.L. (1996). Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex. J. Physiol. 490, 529–536.10.1113/jphysiol.1996.sp021164Search in Google Scholar PubMed PubMed Central
Hall, S.D., Stanford, I.M., Yamawaki, N., McAllister, C.J., Ronnqvist, K.C., Woodhall, G.L., and Furlong, P.L. (2011). The role of GABAergic modulation in motor function related neuronal network activity. Neuroimage 56, 1506–1510.10.1016/j.neuroimage.2011.02.025Search in Google Scholar PubMed
Harrison, N.A., Brydon, L., Walker, C., Gray, M.A., Steptoe, A., Dolan, R.J., and Critchley, H.D. (2009). Neural origins of human sickness in interoceptive responses to inflammation. Biol. Psychiatry 66, 415–122.10.1016/j.biopsych.2009.03.007Search in Google Scholar PubMed PubMed Central
Hilty, L., Jancke, L., Luechinger, R., Boutellier, U., and Lutz, K. (2011). Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo-insular activity. Hum. Brain Mapp. 32, 2151–2160.10.1002/hbm.21177Search in Google Scholar PubMed PubMed Central
Holtzer, R., Shuman, M., Mahoney, J.R., Lipton, R., and Verghese, J. (2011). Cognitive fatigue defined in the context of attention networks. Neuropsychol. Dev. Cogn. B Aging Neuropsychol. Cogn. 18, 108–128.10.1080/13825585.2010.517826Search in Google Scholar PubMed PubMed Central
Ishii, A., Tanaka, M., Yamano, E., and Watanabe, Y. (2012). Neural substrates activated by viewing others expressing fatigue: a magnetoencephalography study. Brain Res. 1455, 68–74.10.1016/j.brainres.2012.03.031Search in Google Scholar
Ishii, A., Tanaka, M., Iwamae, M., Kim, C., Yamano, E., and Watanabe, Y. (2013). Fatigue sensation induced by the sounds associated with mental fatigue and its related neural activities: revealed by magnetoencephalography. Behav. Brain Funct. 9, 24.10.1186/1744-9081-9-24Search in Google Scholar
Ishii, A., Tanaka, M., and Watanabe, Y. (2014a). The neural substrates of self-evaluation of mental fatigue: a magnetoencephalography study. PLoS One 9, e95763.10.1371/journal.pone.0095763Search in Google Scholar
Ishii, A., Tanaka, M., Yamano, E., and Watanabe, Y. (2014b). The neural substrates of physical fatigue sensation to evaluate ourselves: a magnetoencephalography study. Neuroscience 261, 60–67.10.1016/j.neuroscience.2013.12.049Search in Google Scholar
Jasmin, L., Rabkin, S.D., Granato, A., Boudah, A., and Ohara, P.T. (2003). Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex. Nature 424, 316–320.10.1038/nature01808Search in Google Scholar
Jensen, O., Goel, P., Kopell, N., Pohja, M., Hari, R., and Ermentrout, B. (2005). On the human sensorimotor-cortex beta rhythm: sources and modeling. Neuroimage 26, 347–355.10.1016/j.neuroimage.2005.02.008Search in Google Scholar
Johnson, S.C., Baxter, L.C., Wilder, L.S., Pipe, J.G., Heiserman, J.E., and Prigatano, G.P. (2002). Neural correlates of self-reflection. Brain 125, 1808–1814.10.1093/brain/awf181Search in Google Scholar
Johnson, S.A., Yechiam, E., Murphy, R.R., Queller, S., and Stout, J.C. (2006). Motivational processes and autonomic responsivity in Asperger’s disorder: evidence from the Iowa Gambling Task. J. Int. Neuropsychol. Soc. 12, 668–676.10.1017/S1355617706060802Search in Google Scholar
Johnston, J., Rearick, M., and Slobounov, S. (2001). Movement-related cortical potentials associated with progressive muscle fatigue in a grasping task. Clin. Neurophysiol. 112, 68–77.10.1016/S1388-2457(00)00452-1Search in Google Scholar
Jouanin, J.C., Peres, M., Ducorps, A., and Renault, B. (2009). A dynamic network involving M1-S1, SII-insular, medial insular, and cingulate cortices controls muscular activity during an isometric contraction reaction time task. Hum. Brain Mapp. 30, 675–688.10.1002/hbm.20534Search in Google Scholar PubMed PubMed Central
Kajimoto, O. (2007). Development of a method of evaluation of fatigue and its economic impacts. Fatigue Science for Human Health. Y. Watanabe, B. Evengard, B.H. Natelson, L. Jason, and H. Kuratsune, eds. (New York: Springer), pp. 33–46.Search in Google Scholar
Katafuchi, T. (2004). Conditioning of fatigue and serotonin system. Mol. Med. 41, 1264–1268 (in Japanese).Search in Google Scholar
Kato, T., Murashita, J., Shioiri, T., Inubushi, T., and Kato, N. (1999). Relationship of energy metabolism detected by 31P-MRS in the human brain with mental fatigue. Neuropsychobiology 39, 214–218.10.1159/000026587Search in Google Scholar
Kato, Y., Endo, H., and Kizuka, T. (2009). Mental fatigue and impaired response processes: event-related brain potentials in a Go/NoGo task. Int. J. Psychophysiol. 72, 204–211.10.1016/j.ijpsycho.2008.12.008Search in Google Scholar
Kircher, T.T., Brammer, M., Bullmore, E., Simmons, A., Bartels, M., and David, A.S. (2002). The neural correlates of intentional and incidental self processing. Neuropsychologia 40, 683–692.10.1016/S0028-3932(01)00138-5Search in Google Scholar
Kitani, T. (2011). Term Committee of Japanese Society of Fatigue Science. Nihon Hirougakkaishi 6, 1 (in Japanese).Search in Google Scholar
Korotkov, A., Radovanovic, S., Ljubisavljevic, M., Lyskov, E., Kataeva, G., Roudas, M., Pakhomov, S., Thunberg, J., Medvedev, S., and Johansson, H. (2005). Comparison of brain activation after sustained non-fatiguing and fatiguing muscle contraction: a positron emission tomography study. Exp. Brain Res. 163, 65–74.10.1007/s00221-004-2141-5Search in Google Scholar
Kumar, V.M. (2008). Sleep and sleep disorders. Indian J. Chest Dis. Allied Sci. 50, 129–135.Search in Google Scholar
Lange, G., Steffener, J., Cook, D.B., Bly, B.M., Christodoulou, C., Liu, W.C., Deluca, J., and Natelson, B.H. (2005). Objective evidence of cognitive complaints in chronic fatigue syndrome: a BOLD fMRI study of verbal working memory. Neuroimage 26, 513–524.10.1016/j.neuroimage.2005.02.011Search in Google Scholar
Langner, R., Steinborn, M.B., Chatterjee, A., Sturm, W., and Willmes, K. (2010). Mental fatigue and temporal preparation in simple reaction-time performance. Acta Psychol. (Amst.) 133, 64–72.10.1016/j.actpsy.2009.10.001Search in Google Scholar
Lee, K.A., Hicks, G., and Nino-Murcia, G. (1991). Validity and reliability of a scale to assess fatigue. Psychiatry Res. 36, 291–298.10.1016/0165-1781(91)90027-MSearch in Google Scholar
Lim, J., Wu, W.C., Wang, J., Detre, J.A., Dinges, D.F., and Rao, H. (2010). Imaging brain fatigue from sustained mental workload: an ASL perfusion study of the time-on-task effect. Neuroimage 49, 3426–3435.10.1016/j.neuroimage.2009.11.020Search in Google Scholar PubMed PubMed Central
Liu, J.Z., Shan, Z.Y., Zhang, L.D., Sahgal, V., Brown, R.W., and Yue, G.H. (2003). Human brain activation during sustained and intermittent submaximal fatigue muscle contractions: an FMRI study. J. Neurophysiol. 90, 300–312.10.1152/jn.00821.2002Search in Google Scholar PubMed
Liu, J.Z., Lewandowski, B., Karakasis, C., Yao, B., Siemionow, V., Sahgal, V., and Yue, G.H. (2007). Shifting of activation center in the brain during muscle fatigue: an explanation of minimal central fatigue? Neuroimage 35, 299–307.10.1016/j.neuroimage.2006.09.050Search in Google Scholar PubMed PubMed Central
Lopes da Silva, F. (1991). Neural mechanisms underlying brain waves: from neural membranes to networks. Electroencephalogr. Clin. Neurophysiol. 79, 81–93.10.1016/0013-4694(91)90044-5Search in Google Scholar
Lorist, M.M. (2008). Impact of top-down control during mental fatigue. Brain Res. 1232, 113–123.10.1016/j.brainres.2008.07.053Search in Google Scholar PubMed
Lorist, M.M., Klein, M., Nieuwenhuis, S., De Jong, R., Mulder, G., and Meijman, T.F. (2000). Mental fatigue and task control: planning and preparation. Psychophysiology 37, 614–625.10.1111/1469-8986.3750614Search in Google Scholar
Lorist, M.M., Boksem, M.A., and Ridderinkhof, K.R. (2005). Impaired cognitive control and reduced cingulate activity during mental fatigue. Brain Res. Cogn. Brain Res. 24, 199–205.10.1016/j.cogbrainres.2005.01.018Search in Google Scholar PubMed
Lorist, M.M., Bezdan, E., ten Caat, M., Span, M.M., Roerdink, J.B., and Maurits, N.M. (2009). The influence of mental fatigue and motivation on neural network dynamics; an EEG coherence study. Brain Res. 1270, 95–106.10.1016/j.brainres.2009.03.015Search in Google Scholar PubMed
Lutz, J., Jager, L., de Quervain, D., Krauseneck, T., Padberg, F., Wichnalek, M., Beyer, A., Stahl, R., Zirngibl, B., Morhard, D., et al. (2008). White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 58, 3960–3969.10.1002/art.24070Search in Google Scholar PubMed
Malliani, A., Pagani, M., Lombardi, F., and Cerutti, S. (1991). Cardiovascular neural regulation explored in the frequency domain. Circulation 84, 482–492.10.1161/01.CIR.84.2.482Search in Google Scholar PubMed
Marcora, S.M., Staiano, W., and Manning, V. (2009). Mental fatigue impairs physical performance in humans. J. Appl. Physiol. (1985) 106, 857–864.10.1152/japplphysiol.91324.2008Search in Google Scholar PubMed
Massar, S.A., Wester, A.E., Volkerts, E.R., and Kenemans, J.L. (2010). Manipulation specific effects of mental fatigue: evidence from novelty processing and simulated driving. Psychophysiology 47, 1119–1126.10.1111/j.1469-8986.2010.01028.xSearch in Google Scholar PubMed
Matthews, G. and Desmond, P.A. (2002). Task-induced fatigue states and simulated driving performance. Q. J. Exp. Psychol. A 55, 659–686.10.1080/02724980143000505Search in Google Scholar PubMed
Mavjee, V. and Horne, J.A. (1994). Boredom effects on sleepiness/alertness in the early afternoon vs. early evening and interactions with warm ambient temperature. Br. J. Psychol. 85, 317–333.10.1111/j.2044-8295.1994.tb02527.xSearch in Google Scholar PubMed
Mezzacappa, E., Kindlon, D., Saul, J.P., and Earls, F. (1998). Executive and motivational control of performance task behavior, and autonomic heart-rate regulation in children: physiologic validation of two-factor solution inhibitory control. J. Child Psychol. Psychiatry 39, 525–331.10.1017/S0021963098002273Search in Google Scholar
Milesi, M.A., Lacan, D., Brosse, H., Desor, D., and Notin, C. (2009). Effect of an oral supplementation with a proprietary melon juice concentrate (Extramel) on stress and fatigue in healthy people: a pilot, double-blind, placebo-controlled clinical trial. Nutr. J. 8, 40.10.1186/1475-2891-8-40Search in Google Scholar PubMed PubMed Central
Mizuno, K. and Watanabe, Y. (2007). Utility of an advanced trail making test as a neuropsychological tool for an objective evaluation of work efficiency during mental fatigue. Fatigue Science for Human Health. Y. Watanabe, B. Evengård, B. Natelson, L. Jason, H. Kuratsune, eds. (New York: Springer), pp. 5–11.Search in Google Scholar
Murthy, V.N. and Fetz, E.E. (1996). Oscillatory activity in sensorimotor cortex of awake monkeys: synchronization of local field potentials and relation to behavior. J. Neurophysiol. 76, 3949–3967.10.1152/jn.1996.76.6.3949Search in Google Scholar PubMed
Nakagawa, S., Sugiura, M., Akitsuki, Y., Hosseini, S.M., Kotozaki, Y., Miyauchi, C.M., Yomogida, Y., Yokoyama, R., Takeuchi, H., and Kawashima, R. (2013). Compensatory effort parallels midbrain deactivation during mental fatigue: an fMRI study. PLoS One 8, e56606.10.1371/journal.pone.0056606Search in Google Scholar PubMed PubMed Central
Ohara, P.T., Vit, J.P., and Jasmin, L. (2005). Cortical modulation of pain. Cell. Mol. Life Sci. 62, 44–52.10.1007/s00018-004-4283-9Search in Google Scholar PubMed
Okada, T., Tanaka, M., Kuratsune, H., Watanabe, Y., and Sadato, N. (2004). Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 4, 14.10.1186/1471-2377-4-14Search in Google Scholar PubMed PubMed Central
Otto, T., Zijlstra, F.R., and Goebel, R. (2013). Neural correlates of mental effort evaluation – involvement of structures related to self-awareness. Soc. Cogn. Affect. Neurosci. 9, 307–315.10.1093/scan/nss136Search in Google Scholar PubMed PubMed Central
Pagani, M., Montano, N., Porta, A., Malliani, A., Abboud, F.M., Birkett, C., and Somers, V.K. (1997). Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95, 1441–1448.10.1161/01.CIR.95.6.1441Search in Google Scholar PubMed
Pageaux, B., Marcora, S.M., and Lepers, R. (2013). Prolonged mental exertion does not alter neuromuscular function of the knee extensors. Med. Sci. Sports Exerc. in press (Epub ahead of print).10.1249/MSS.0b013e31829b504aSearch in Google Scholar PubMed
Pauly, D.F. and Pepine, C.J. (2000). D-Ribose as a supplement for cardiac energy metabolism. J. Cardiovasc. Pharmacol. Ther. 5, 249–258.10.1054/JCPT.2000.18011Search in Google Scholar PubMed
Pomeranz, B., Macaulay, R.J., Caudill, M.A., Kutz, I., Adam, D., Gordon, D., Kilborn, K.M., Barger, A.C., Shannon, D.C., Cohen, R.J., et al. (1985). Assessment of autonomic function in humans by heart rate spectral analysis. Am. J. Physiol. 248, H151–H153.10.1152/ajpheart.1985.248.1.H151Search in Google Scholar PubMed
Post, M., Steens, A., Renken, R., Maurits, N.M., and Zijdewind, I. (2009). Voluntary activation and cortical activity during a sustained maximal contraction: an fMRI study. Hum. Brain Mapp. 30, 1014–1027.10.1002/hbm.20562Search in Google Scholar PubMed PubMed Central
Rinzel, J., Terman, D., Wang, X., and Ermentrout, B. (1998). Propagating activity patterns in large-scale inhibitory neuronal networks. Science. 279, 1351–1355.10.1126/science.279.5355.1351Search in Google Scholar PubMed
Roelcke, U., Kappos, L., Lechner-Scott, J., Brunnschweiler, H., Huber, S., Ammann, W., Plohmann, A., Dellas, S., Maguire, R.P., Missimer, J., et al. (1997). Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48, 1566–1571.10.1212/WNL.48.6.1566Search in Google Scholar
Ruehle, B.S., Handwerker, H.O., Lennerz, J.K., Ringler, R., and Forster, C. (2006). Brain activation during input from mechanoinsensitive versus polymodal C-nociceptors. J. Neurosci. 26, 5492–5499.10.1523/JNEUROSCI.2059-05.2006Search in Google Scholar PubMed PubMed Central
Shigihara, Y., Tanaka, M., Ishii, A., Kanai, E., Funakura, M., and Watanabe, Y. (2013a). Two types of mental fatigue affect spontaneous oscillatory brain activities in different ways. Behav. Brain Funct. 9, 2.10.1186/1744-9081-9-2Search in Google Scholar PubMed PubMed Central
Shigihara, Y., Tanaka, M., Ishii, A., Tajima, S., Kanai, E., Funakura, M., and Watanabe, Y. (2013b). Two different types of mental fatigue produce different styles of task performance. Neurol. Psychiatry Brain Res. 19, 5–11.10.1016/j.npbr.2012.07.002Search in Google Scholar
Smith, E.E. and Jonides, J. (1999). Storage and executive processes in the frontal lobes. Science 283, 1657–1661.10.1126/science.283.5408.1657Search in Google Scholar PubMed
St Clair Gibson, A., Baden, D.A., Lambert, M.I., Lambert, E.V., Harley, Y.X., Hampson, D., Russell, V.A., and Noakes, T.D. (2003). The conscious perception of the sensation of fatigue. Sports Med. 33, 167–176.10.2165/00007256-200333030-00001Search in Google Scholar PubMed
Tanaka, M. and Watanabe, Y. (2010). A new hypothesis of chronic fatigue syndrome: co-conditioning theory. Med. Hypotheses 75, 244–249.10.1016/j.mehy.2010.02.032Search in Google Scholar PubMed
Tanaka, M. and Watanabe, Y. (2011). Neural compensation mechanisms to regulate motor output during physical fatigue. Brain Res. 1395, 46–52.10.1016/j.brainres.2011.04.041Search in Google Scholar PubMed
Tanaka, M. and Watanabe, Y. (2012). Supraspinal regulation of physical fatigue. Neurosci. Biobehav. Rev. 36, 727–734.10.1016/j.neubiorev.2011.10.004Search in Google Scholar PubMed
Tanaka, M., Sadato, N., Okada, T., Mizuno, K., Sasabe, T., Tanabe, H.C., Saito, D.N., Onoe, H., Kuratsune, H., and Watanabe, Y. (2006). Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study. BMC Neurol. 6, 9.10.1186/1471-2377-6-9Search in Google Scholar PubMed PubMed Central
Tanaka, M., Mizuno, K., Tajima, S., Sasabe, T., and Watanabe, Y. (2009). Central nervous system fatigue alters autonomic nerve activity. Life Sci. 84, 235–239.10.1016/j.lfs.2008.12.004Search in Google Scholar PubMed
Tanaka, M., Shigihara, Y., and Watanabe, Y. (2011). Central inhibition regulates motor output during physical fatigue. Brain Res. 1412, 37–43.10.1016/j.brainres.2011.07.021Search in Google Scholar PubMed
Tanaka, M., Ishii, A., Shigihara, Y., Tajima, S., Funakura, M., Kanai, E., and Watanabe, Y. (2012). Impaired selective attention caused by mental fatigue. J. Neurol. Sci. (Turkish) 29, 542–553.Search in Google Scholar
Tanaka, M., Ishii, A., and Watanabe, Y. (2013). Neural correlates of central inhibition during physical fatigue. PLoS One 8, e70949.10.1371/journal.pone.0070949Search in Google Scholar PubMed PubMed Central
Tanaka, M., Ishii, A., and Watanabe, Y. (2014). Regulatory mechanism of performance in chronic cognitive fatigue. Med. Hypotheses 82, 567–571.10.1016/j.mehy.2014.02.013Search in Google Scholar PubMed
Taylor, J.L. and Gandevia, S.C. (2008). A comparison of central aspects of fatigue in submaximal and maximal voluntary contractions. J. Appl. Physiol. (1985) 104, 542–550.10.1152/japplphysiol.01053.2007Search in Google Scholar PubMed
Taylor, J.L., Butler, J.E., Allen, G.M., and Gandevia, S.C. (1996). Changes in motor cortical excitability during human muscle fatigue. J. Physiol. 490, 519–528.10.1113/jphysiol.1996.sp021163Search in Google Scholar PubMed PubMed Central
van der Linden, D. and Eling, P. (2006). Mental fatigue disturbs local processing more than global processing. Psychol. Res. 70, 395–402.10.1007/s00426-005-0228-7Search in Google Scholar
van der Linden, D., Frese, M., and Meijman, T.F. (2003a). Mental fatigue and the control of cognitive processes: effects on perseveration and planning. Acta Psychol. (Amst.) 113, 45–65.10.1016/S0001-6918(02)00150-6Search in Google Scholar
van der Linden, D., Frese, M., and Sonnentag, S. (2003b). The impact of mental fatigue on exploration in a complex computer task: rigidity and loss of systematic strategies. Hum. Factors 45, 483–494.10.1518/hfes.45.3.483.27256Search in Google Scholar
Varela, F., Lachaux, J.P., Rodriguez, E., and Martinerie, J. (2001). The brainweb: phase synchronization and large-scale integration. Nat. Rev. Neurosci. 2, 229–239.10.1038/35067550Search in Google Scholar
Vogt, B.A. and Laureys, S. (2005). Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness. Prog. Brain Res. 150, 205–217.10.1016/S0079-6123(05)50015-3Search in Google Scholar
Vogt, B.A., Vogt, L., and Laureys, S. (2006). Cytology and functionally correlated circuits of human posterior cingulate areas. Neuroimage 29, 452–466.10.1016/j.neuroimage.2005.07.048Search in Google Scholar PubMed PubMed Central
White, A.T., Lee, J.N., Light, A.R., and Light, K.C. (2009). Brain activation in multiple sclerosis: a BOLD fMRI study of the effects of fatiguing hand exercise. Mult. Scler. 15, 580–586.10.1177/1352458508100034Search in Google Scholar PubMed
Yamamoto, S., Ouchi, Y., Onoe, H., Yoshikawa, E., Tsukada, H., Takahashi, H., Iwase, M., Yamaguti, K., Kuratsune, H., and Watanabe, Y. (2004). Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport 15, 2571–2574.10.1097/00001756-200412030-00002Search in Google Scholar PubMed
Yamawaki, N., Stanford, I.M., Hall, S.D., and Woodhall, G.L. (2008). Pharmacologically induced and stimulus evoked rhythmic neuronal oscillatory activity in the primary motor cortex in vitro. Neuroscience 151, 386–395.10.1016/j.neuroscience.2007.10.021Search in Google Scholar PubMed
Zhuo, M. (2008). Cortical excitation and chronic pain. Trends Neurosci. 31, 199–207.10.1016/j.tins.2008.01.003Search in Google Scholar PubMed
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