Abstract
According to best current estimates, approximately 10% of those infected with SARS-CoV-2-virus experience long-term clinical and nonspecific neurological symptoms that may last for several weeks or months. This is currently referred to as “Long-COVID” or “Post-COVID-Syndrome”. Based on current knowledge, the most common long-term symptoms of COVID-19 disease include fatigue and poor concentration, but particularly also headache and musculoskeletal pain. However, given the novelty of COVID-19, only a few studies have systematically evaluated the central nervous alterations in the pain processing structures of our brain. Those first insights are yet important in order to offer patients adequate therapeutic options. Based on a systematic review of the literature, we will therefore provide an overview of the central nervous alterations in the brain described in the context of SARS-CoV-2 infection, focusing on findings with brain imaging.
Zusammenfassung
Nach aktuellen Schätzungen treten bei etwa 10% der mit dem SARS-CoV-2-Virus Infizierten klinische und unspezifische neurologische Symptome auf, die mehrere Wochen oder Monate andauern können. Dies wird aktuell als „Long-COVID“ oder „Post-COVID-Syndrom“ bezeichnet. Nach derzeitigem Kenntnisstand zählen Fatigue, Konzentrationsschwäche, Kopf-, und muskuloskelettale Schmerzen zu den häufigsten Spätsymptomen einer COVID-19-Erkrankung. Angesichts der Neuartigkeit von COVID-19 existieren bisher nur wenige Studien, die zentralnervöse Veränderungen in schmerzverarbeitenden Strukturen des Gehirns systematisch untersucht haben. Diese ersten Erkenntnisse sind jedoch bereits wichtig, um Betroffenen optimale Therapieoptionen bieten zu können. Ausgehend von einer systematischen Literatursuche geben wir daher einen Überblick über die im Rahmen einer SARS-CoV-2-Infektion beschriebenen zentralnervösen Veränderungen im Gehirn, wobei der Fokus auf Befunden mit bildgebender Darstellung des Gehirns liegt.
Funding source: German Research Foundation
Award Identifier / Grant number: 1158
Funding source: German Federal Ministry of Education and Research
Award Identifier / Grant number: FKZ:01 EC1904A
About the authors
Jonas Tesarz is a specialist in internal medicine and currently works as managing senior physician and associate professor at Heidelberg University Hospital, Department of General Internal Medicine and Psychosomatics. After completing his PhD at the University of Heidelberg on the neurobiology of pain processing, he initially focused on researching the role of myofascial tissue in the development and maintenance of low back pain before starting his clinical practice at the Department of General Internal Medicine and Psychosomatics (Division of Musculoskeletal Pain) at the University of Heidelberg. There he habilitated on the influence of biopsychosocial factors on chronic low back pain. In addition to researching the influence of traumatic life events on pain processing, his particular scientific interest lies in the development and scientific evaluation of novel psychological treatment approaches for the treatment of chronic pain conditions.
Frauke Nees is Full Professor of Medical Psychology and Behavioral Neurobiology, Medical Faculty, Kiel University, and Director of the Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Campus Kiel. She was trained in psychology, psychobiology and cognitive and clinical neuroscience in Landau, Trier and the Cenral Institute of Mental Health Mannheim, Heidelberg University, and holds the venia legendi in Neuropsychology, Clinical Psychology and Medical Psychology from the Medical Faculty Mannheim, Heidelberg University.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: The submitted article does not contain information about medical device(s)/drug(s). This work was supported by German Research Foundation (DFG) within the Collaborative Research Center (SFB) 1158 (projects B03 and B04) and by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; PerPAIN consortium, FKZ:01 EC1904A). No benefits in any form have been or will be received from a commercial party directly or indirectly related to the subject of this article.
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Conflict of interest statement: The authors have no conflicts of interest to declare.
References
Agarwal, S., Melmed, K., Dogra, S., Jain, R., Conway, J., Galetta, S., and Lewis, A. (2021). Increase in ventricle size and the evolution of white matter changes on serial imaging in critically ill patients with COVID-19. Neurocrit. Care 35, 491–500, https://doi.org/10.1007/s12028-021-01207-2.Search in Google Scholar
Al-Sarraj, S., Troakes, C., Hanley, B., Osborn, M., Richardson, M.P., Hotopf, M., Bullmore, E., and Everall, I.P. (2021). Invited Review: The spectrum of neuropathology in COVID-19. Neuropathol. Appl. Neurobiol. 47, 3–16, https://doi.org/10.1111/nan.12667.Search in Google Scholar
Alexander, G.E., Newman, J.D., and Symmes, D. (1976). Convergence of prefrontal and acoustic inputs upon neurons in the superior temporal gyrus of the awake squirrel monkey. Brain Res. 116, 334–338, https://doi.org/10.1016/0006-8993(76)90913-6.Search in Google Scholar
Apkarian, A.V., Baliki, M.N., and Geha, P.Y. (2009). Towards a theory of chronic pain. Prog. Neurobiol. 87, 81–97, https://doi.org/10.1016/j.pneurobio.2008.09.018.Search in Google Scholar PubMed PubMed Central
Baliki, M.N., Mansour, A.R., Baria, A.T., and Apkarian, A.V. (2014). Functional reorganization of the default mode network across chronic pain conditions. PLoS One 9, e106133, https://doi.org/10.1371/journal.pone.0106133.Search in Google Scholar PubMed PubMed Central
Baliki, M.N., Petre, B., Torbey, S., Herrmann, K.M., Huang, L., Schnitzer, T.J., Fields, H.L., and Apkarian, A.V. (2012). Corticostriatal functional connectivity predicts transition to chronic back pain. Nat. Neurosci. 15, 1117–1119, https://doi.org/10.1038/nn.3153.Search in Google Scholar PubMed PubMed Central
Banich, M.T. (1998). The missing link: The role of interhemispheric interaction in attentional processing. Brain Cognit. 36, 128–157, https://doi.org/10.1006/brcg.1997.0950.Search in Google Scholar PubMed
Bantick, S.J., Wise, R.G., Ploghaus, A., Clare, S., Smith, S.M., and Tracey, I. (2002). Imaging how attention modulates pain in humans using functional MRI. Brain 125, 310–319, https://doi.org/10.1093/brain/awf022.Search in Google Scholar PubMed
Benedetti, F., Mayberg, H.S., Stohler, C.S., and Zubieta, J.-K. (2005). Neurobiological mechanisms of the placebo effect. J. Neurosci. 25, 10390–10402, https://doi.org/10.1523/jneurosci.3458-05.2005.Search in Google Scholar PubMed PubMed Central
Benedetti, F., Palladini, M., Paolini, M., Melloni, E., Vai, B., De Lorenzo, R., Furlan, R., Rovere-Querini, P., Falini, A., and Mazza, M.G. (2021). Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study. Brain Behav. Immun. Health 18, 100387, https://doi.org/10.1016/j.bbih.2021.100387.Search in Google Scholar PubMed PubMed Central
Bingel, U., Wanigasekera, V., Wiech, K., Ni Mhuircheartaigh, R., Lee, M.C., Ploner, M., and Tracey, I. (2011). The effect of treatment expectation on drug efficacy: Imaging the analgesic benefit of the opioid remifentanil. Sci. Transl. Med. 3, 70ra14, https://doi.org/10.1126/scitranslmed.3001244.Search in Google Scholar
Borsook, D., Sava, S., and Becerra, L. (2010). The pain imaging revolution: Advancing pain into the 21st century. Neuroscientist 16, 171–185, https://doi.org/10.1177/1073858409349902.Search in Google Scholar
Borsook, D., Veggeberg, R., Erpelding, N., Borra, R., Linnman, C., Burstein, R., and Becerra, L. (2016). The insula: A “hub of activity” in migraine. Neuroscientist 22, 632–652, https://doi.org/10.1177/1073858415601369.Search in Google Scholar
Boutros, N.N. and Belger, A. (1999). Midlatency evoked potentials attenuation and augmentation reflect different aspects of sensory gating. Biol. Psychiatr. 45, 917–922, https://doi.org/10.1016/s0006-3223(98)00253-4.Search in Google Scholar
Bushnell, M.C., Duncan, G.H., Hofbauer, R.K., Ha, B., Chen, J.I., and Carrier, B. (1999). Pain perception: Is there a role for primary somatosensory cortex? Proc. Natl. Acad. Sci. U. S. A. 96, 7705–7709, https://doi.org/10.1073/pnas.96.14.7705.Search in Google Scholar PubMed PubMed Central
Cagnie, B., Coppieters, I., Denecker, S., Six, J., Danneels, L., and Meeus, M. (2014). Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI. Semin. Arthritis Rheum. 44, 68–75, https://doi.org/10.1016/j.semarthrit.2014.01.001.Search in Google Scholar PubMed
Chougar, L., Shor, N., Weiss, N., Galanaud, D., Leclercq, D., Mathon, B., Belkacem, S., Ströer, S., Burrel, S., Boutolleau, D., et al.. (2020). Retrospective observational study of brain MRI findings in patients with acute SARS-CoV-2 infection and neurologic manifestations. Radiology 297, E313–e323, https://doi.org/10.1148/radiol.2020202422.Search in Google Scholar PubMed PubMed Central
Clarke, S., Kraftsik, R., Van der Loos, H., and Innocenti, G.M. (1989). Forms and measures of adult and developing human corpus callosum: Is there sexual dimorphism? J. Comp. Neurol. 280, 213–230, https://doi.org/10.1002/cne.902800205.Search in Google Scholar PubMed
Colombo, D., Falasca, L., Marchioni, L., Tammaro, A., Adebanjo, G.A.R., Ippolito, G., Zumla, A., Piacentini, M., Nardacci, R., and Del Nonno, F. (2021). Neuropathology and inflammatory cell characterization in 10 autoptic COVID-19 brains. Cells 10, 2262, doi:https://doi.org/10.3390/cells10092262.Search in Google Scholar PubMed PubMed Central
Conklin, J., Frosch, M.P., Mukerji, S.S., Rapalino, O., Maher, M.D., Schaefer, P.W., Lev, M.H., Gonzalez, R.G., Das, S., Champion, S.N., et al.. (2021). Susceptibility-weighted imaging reveals cerebral microvascular injury in severe COVID-19. J. Neurol. Sci. 421, 117308, https://doi.org/10.1016/j.jns.2021.117308.Search in Google Scholar PubMed PubMed Central
Dai, Q., Zhang, Z., Liu, Q., and Yu, H. (2016). The protective effect of olfactory ensheathing cells on post-injury spiral ganglion cells. Acta Otolaryngol. 136, 1115–1120, https://doi.org/10.1080/00016489.2016.1186834.Search in Google Scholar
Dal Ben, D., Marchenkova, A., Thomas, A., Lambertucci, C., Spinaci, A., Marucci, G., Nistri, A., and Volpini, R. (2017). 2’,3’-O-Substituted ATP derivatives as potent antagonists of purinergic P2X3 receptors and potential analgesic agents. Purinergic Signal. 13, 61–74, https://doi.org/10.1007/s11302-016-9539-y.Search in Google Scholar
Davis, K.D. and Moayedi, M. (2013). Central mechanisms of pain revealed through functional and structural MRI. J. Neuroimmune Pharmacol. 8, 518–534, https://doi.org/10.1007/s11481-012-9386-8.Search in Google Scholar
Duan, K., Premi, E., Pilotto, A., Cristillo, V., Benussi, A., Libri, I., Giunta, M., Bockholt, H.J., Liu, J., Campora, R., et al.. (2021). Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19. Neurobiol. Stress 14, 100326, https://doi.org/10.1016/j.ynstr.2021.100326.Search in Google Scholar
Edinger, H.M., Siegel, A., and Troiano, R. (1975). Effect of stimulation of prefrontal cortex and amygdala on diencephalic neurons. Brain Res. 97, 17–31, https://doi.org/10.1016/0006-8993(75)90911-7.Search in Google Scholar
Ermis, U., Rust, M.I., Bungenberg, J., Costa, A., Dreher, M., Balfanz, P., Marx, G., Wiesmann, M., Reetz, K., Tauber, S.C., and Schulz, J.B. (2021). Neurological symptoms in COVID-19: A cross-sectional monocentric study of hospitalized patients. Neurol. Res. Pract. 3, 17, https://doi.org/10.1186/s42466-021-00116-1.Search in Google Scholar PubMed PubMed Central
Fernández-de-Las-Peñas, C., Navarro-Santana, M., Gómez-Mayordomo, V., Cuadrado, M.L., García-Azorín, D., Arendt-Nielsen, L., and Plaza-Manzano, G. (2021a). Headache as an acute and post-COVID-19 symptom in COVID-19 survivors: A meta-analysis of the current literature. Eur. J. Neurol. 28, 3820–3825, https://doi.org/10.1111/ene.15040.Search in Google Scholar PubMed PubMed Central
Fernández-de-Las-Peñas, C., Navarro-Santana, M., Plaza-Manzano, G., Palacios-Ceña, D., and Arendt-Nielsen, L. (2021b). Time course prevalence of post-COVID pain symptoms of musculoskeletal origin in patients who had survived to severe acute respiratory syndrome coronavirus 2 infection: A systematic review and meta-analysis. Pain, https://doi.org/10.1097/j.pain.0000000000002496.Search in Google Scholar PubMed
Fitsiori, A., Pugin, D., Thieffry, C., Lalive, P., and Vargas, M.I. (2020). COVID-19 is associated with an unusual pattern of brain microbleeds in critically ill patients. J. Neuroimaging 30, 593–597, https://doi.org/10.1111/jon.12755.Search in Google Scholar PubMed PubMed Central
Flor, H. (2012). New developments in the understanding and management of persistent pain. Curr. Opin. Psychiatr. 25, 109–113, https://doi.org/10.1097/YCO.0b013e3283503510.Search in Google Scholar PubMed
Frankenstein, U.N., Richter, W., McIntyre, M.C., and Rémy, F. (2001). Distraction modulates anterior cingulate gyrus activations during the cold pressor test. Neuroimage 14, 827–836, https://doi.org/10.1006/nimg.2001.0883.Search in Google Scholar
Friedrich, O., Reid, M.B., Van den Berghe, G., Vanhorebeek, I., Hermans, G., Rich, M.M., and Larsson, L. (2015). The sick and the weak: Neuropathies/myopathies in the critically ill. Physiol. Rev. 95, 1025–1109, https://doi.org/10.1152/physrev.00028.2014.Search in Google Scholar
Gazzaniga, M.S. (1995). Principles of human brain organization derived from split-brain studies. Neuron 14, 217–228, https://doi.org/10.1016/0896-6273(95)90280-5.Search in Google Scholar
Gogia, B., Thottempudi, N., Ajam, Y., Singh, A., Ghanayem, T., Dabi, A., Fang, X., Masel, T., and Rai, P. (2021). EEG characteristics in COVID-19 survivors and non-survivors with seizures and encephalopathy. Cureus 13, e18476, https://doi.org/10.7759/cureus.18476.Search in Google Scholar PubMed PubMed Central
Goudman, L., De Smedt, A., Noppen, M., and Moens, M. (2021). Is central sensitisation the missing link of persisting symptoms after COVID-19 infection? J. Clin. Med. 10, 5594, doi:https://doi.org/10.3390/jcm10235594.Search in Google Scholar PubMed PubMed Central
Gracely, R.H., Petzke, F., Wolf, J.M., and Clauw, D.J. (2002). Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 46, 1333–1343, https://doi.org/10.1002/art.10225.Search in Google Scholar PubMed
Guedj, E., Cammilleri, S., Niboyet, J., Dupont, P., Vidal, E., Dropinski, J.P., and Mundler, O. (2008). Clinical correlate of brain SPECT perfusion abnormalities in fibromyalgia. J. Nucl. Med. 49, 1798–1803, https://doi.org/10.2967/jnumed.108.053264.Search in Google Scholar PubMed
Guedj, E., Campion, J.Y., Dudouet, P., Kaphan, E., Bregeon, F., Tissot-Dupont, H., Guis, S., Barthelemy, F., Habert, P., Ceccaldi, M., et al.. (2021). (18)F-FDG brain PET hypometabolism in patients with long COVID. Eur. J. Nucl. Med. Mol. Imag. 48, 2823–2833, https://doi.org/10.1007/s00259-021-05215-4.Search in Google Scholar PubMed PubMed Central
Gur, A., Karakoc, M., Erdogan, S., Nas, K., Cevik, R., and Sarac, A.J. (2002). Regional cerebral blood flow and cytokines in young females with fibromyalgia. Clin. Exp. Rheumatol. 20, 753–760.Search in Google Scholar
Harris, S. and Rasyid, A. (2020). Objective diagnosis of migraine without aura with migraine vascular index: A novel formula to assess vasomotor reactivity. Ultrasound Med. Biol. 46, 1359–1364, https://doi.org/10.1016/j.ultrasmedbio.2020.01.012.Search in Google Scholar PubMed
Hatanaka, N., Tokuno, H., Hamada, I., Inase, M., Ito, Y., Imanishi, M., Hasegawa, N., Akazawa, T., Nambu, A., and Takada, M. (2003). Thalamocortical and intracortical connections of monkey cingulate motor areas. J. Comp. Neurol. 462, 121–138, https://doi.org/10.1002/cne.10720.Search in Google Scholar PubMed
Hegarty, A.K., Yani, M.S., Albishi, A., Michener, L.A., and Kutch, J.J. (2020). Salience network functional connectivity is spatially heterogeneous across sensorimotor cortex in healthy humans. Neuroimage 221, 117177, https://doi.org/10.1016/j.neuroimage.2020.117177.Search in Google Scholar
Hellgren, L., Birberg Thornberg, U., Samuelsson, K., Levi, R., Divanoglou, A., and Blystad, I. (2021). Brain MRI and neuropsychological findings at long-term follow-up after COVID-19 hospitalisation: An observational cohort study. BMJ Open 11, e055164, https://doi.org/10.1136/bmjopen-2021-055164.Search in Google Scholar
Helms, J., Kremer, S., Merdji, H., Schenck, M., Severac, F., Clere-Jehl, R., Studer, A., Radosavljevic, M., Kummerlen, C., Monnier, A., et al.. (2020). Delirium and encephalopathy in severe COVID-19: A cohort analysis of ICU patients. Crit. Care 24, 491, https://doi.org/10.1186/s13054-020-03200-1.Search in Google Scholar
Kas, A., Soret, M., Pyatigoskaya, N., Habert, M.O., Hesters, A., Le Guennec, L., Paccoud, O., Bombois, S., and Delorme, C. (2021). The cerebral network of COVID-19-related encephalopathy: A longitudinal voxel-based 18F-FDG-PET study. Eur. J. Nucl. Med. Mol. Imag. 48, 2543–2557, https://doi.org/10.1007/s00259-020-05178-y.Search in Google Scholar
Kavak, S., Yildirim, M.S., Altındag, R., Mertsoy, Y., Alakus, M.F., Guleken, M.D., and Kaya, S. (2021). Correlation of neuroimaging findings with clinical presentation and laboratory data in patients with COVID-19: A single-center study. BioMed Res. Int. 2021, 2013371, https://doi.org/10.1155/2021/2013371.Search in Google Scholar
Kelsch, R.D., Silbergleit, R., and Krishnan, A. (2021). Neuroimaging in the first 6 Weeks of the COVID-19 pandemic in an 8-hospital Campus: Observations and patterns in the brain, head and neck, and spine. J. Comput. Assist. Tomogr. 45, 592–599, https://doi.org/10.1097/rct.0000000000001179.Search in Google Scholar
Knight, R.T., Staines, W.R., Swick, D., and Chao, L.L. (1999). Prefrontal cortex regulates inhibition and excitation in distributed neural networks. Acta Psychol. 101, 159–178, https://doi.org/10.1016/s0001-6918(99)00004-9.Search in Google Scholar
Koster-Brouwer, M.E., Rijsdijk, M., van Os, W.K.M., Soliman, I.W., Slooter, A.J.C., de Lange, D.W., van Dijk, D., Bonten, M.J.M., and Cremer, O.L. (2020). Occurrence and risk factors of chronic pain after critical illness. Crit. Care Med. 48, 680–687, https://doi.org/10.1097/ccm.0000000000004259.Search in Google Scholar PubMed
Kregel, J., Meeus, M., Malfliet, A., Dolphens, M., Danneels, L., Nijs, J., and Cagnie, B. (2015). Structural and functional brain abnormalities in chronic low back pain: A systematic review. Semin. Arthritis Rheum. 45, 229–237, https://doi.org/10.1016/j.semarthrit.2015.05.002.Search in Google Scholar PubMed
Kremer, S., Lersy, F., de Sèze, J., Ferré, J.C., Maamar, A., Carsin-Nicol, B., Collange, O., Bonneville, F., Adam, G., Martin-Blondel, G., et al.. (2020). Brain MRI findings in severe COVID-19: A retrospective observational study. Radiology 297, E242–E251, https://doi.org/10.1148/radiol.2020202222.Search in Google Scholar PubMed PubMed Central
Kutch, J.J., Ichesco, E., Hampson, J.P., Labus, J.S., Farmer, M.A., Martucci, K.T., Ness, T.J., Deutsch, G., Apkarian, A.V., Mackey, S.C., et al.. (2017). Brain signature and functional impact of centralized pain: A multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study. Pain 158, 1979–1991, https://doi.org/10.1097/j.pain.0000000000001001.Search in Google Scholar
Lambrecq, V., Hanin, A., Munoz-Musat, E., Chougar, L., Gassama, S., Delorme, C., Cousyn, L., Borden, A., Damiano, M., Frazzini, V., et al.. (2021). Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw. Open 4, e211489, https://doi.org/10.1001/jamanetworkopen.2021.1489.Search in Google Scholar
Lee, M.H., Perl, D.P., Nair, G., Li, W., Maric, D., Murray, H., Dodd, S.J., Koretsky, A.P., Watts, J.A., Cheung, V., et al.. (2021). Microvascular injury in the brains of patients with covid-19. N. Engl. J. Med. 384, 481–483, https://doi.org/10.1056/NEJMc2033369.Search in Google Scholar
Longe, S.E., Wise, R., Bantick, S., Lloyd, D., Johansen-Berg, H., McGlone, F., and Tracey, I. (2001). Counter-stimulatory effects on pain perception and processing are significantly altered by attention: An fMRI study. Neuroreport 12, 2021–2025, https://doi.org/10.1097/00001756-200107030-00047.Search in Google Scholar
Lopez, G., Tonello, C., Osipova, G., Carsana, L., Biasin, M., Cappelletti, G., Pellegrinelli, A., Lauri, E., Zerbi, P., Rossi, R.S., and Nebuloni, M. (2022). Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas. Neuropathol. Appl. Neurobiol. 48, e12752, https://doi.org/10.1111/nan.12752.Search in Google Scholar
Louis, S., Dhawan, A., Newey, C., Nair, D., Jehi, L., Hantus, S., and Punia, V. (2020). Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients. Clin. Neurophysiol. 131, 2651–2656, https://doi.org/10.1016/j.clinph.2020.08.003.Search in Google Scholar
Lu, Y., Li, X., Geng, D., Mei, N., Wu, P.Y., Huang, C.C., Jia, T., Zhao, Y., Wang, D., Xiao, A., and Yin, B. (2020). Cerebral micro-structural changes in COVID-19 patients - an MRI-based 3-month follow-up study. EClinicalMedicine 25, 100484, https://doi.org/10.1016/j.eclinm.2020.100484.Search in Google Scholar
Marcic, L., Marcic, M., Kojundzic, S.L., Marcic, B., Capkun, V., and Vukojevic, K. (2021). Personalized approach to patient with MRI brain changes after SARS-CoV-2 infection. J. Personalized Med. 11, 442, doi:https://doi.org/10.3390/jpm11060442.Search in Google Scholar
Matschke, J., Lütgehetmann, M., Hagel, C., Sperhake, J.P., Schröder, A.S., Edler, C., Mushumba, H., Fitzek, A., Allweiss, L., Dandri, M., et al.. (2020). Neuropathology of patients with COVID-19 in Germany: A post-mortem case series. Lancet Neurol. 19, 919–929, https://doi.org/10.1016/s1474-4422(20)30308-2.Search in Google Scholar
Ornello, R., Frattale, I., Caponnetto, V., Pistoia, F., and Sacco, S. (2020). Cerebral vascular reactivity and the migraine-stroke relationship: A narrative review. J. Neurol. Sci. 414, 116887, https://doi.org/10.1016/j.jns.2020.116887.Search in Google Scholar PubMed
Öztürk, B. and Karadaş, Ö. (2020). Cerebral hemodynamic changes during migraine attacks and after triptan treatments. Noro Psikiyatr Ars. 57, 192–196, https://doi.org/10.29399/npa.21650.Search in Google Scholar
Pastor, J., Vega-Zelaya, L., and Martín Abad, E. (2020). Specific EEG encephalopathy pattern in SARS-CoV-2 patients. J. Clin. Med. 9, https://doi.org/10.3390/jcm9051545.Search in Google Scholar
Paterson, R.W., Paterson, R.W., Brown, R.L., Benjamin, L., Nortley, R., Wiethoff, S., Bharucha, T., Jayaseelan, D.L., Kumar, G., Raftopoulos, R.E., et al.. (2020). The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings. Brain 143, 3104–3120, https://doi.org/10.1093/brain/awaa240.Search in Google Scholar
Pellinen, J., Carroll, E., Friedman, D., Boffa, M., Dugan, P., Friedman, D.E., Gazzola, D., Jongeling, A., Rodriguez, A.J., and Holmes, M. (2020). Continuous EEG findings in patients with COVID-19 infection admitted to a New York academic hospital system. Epilepsia 61, 2097–2105, https://doi.org/10.1111/epi.16667.Search in Google Scholar
Petrovic, P., Petersson, K.M., Ghatan, P.H., Stone-Elander, S., and Ingvar, M. (2000). Pain-related cerebral activation is altered by a distracting cognitive task. Pain 85, 19–30, https://doi.org/10.1016/s0304-3959(99)00232-8.Search in Google Scholar
Pilotto, A., Masciocchi, S., Volonghi, I., Crabbio, M., Magni, E., De Giuli, V., Caprioli, F., Rifino, N., Sessa, M., Gennuso, M., et al.. (2021). Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: The ENCOVID multicenter study. J. Infect. Dis. 223, 28–37, https://doi.org/10.1093/infdis/jiaa609.Search in Google Scholar
Poloni, T.E., Medici, V., Moretti, M., Visonà, S.D., Cirrincione, A., Carlos, A.F., Davin, A., Gagliardi, S., Pansarasa, O., Cereda, C., et al.. (2021). COVID-19-related neuropathology and microglial activation in elderly with and without dementia. Brain Pathol. 31, e12997, https://doi.org/10.1111/bpa.12997.Search in Google Scholar
Qin, Y., Wu, J., Chen, T., Li, J., Zhang, G., Wu, D., Zhou, Y., Zheng, N., Cai, A., and Ning, Q., et al.. (2021). Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations. J. Clin. Invest. 131, e147329, doi:https://doi.org/10.1172/jci147329.Search in Google Scholar
Raman, B., Cassar, M.P., Tunnicliffe, E.M., Filippini, N., Griffanti, L., Alfaro-Almagro, F., Okell, T., Sheerin, F., Xie, C., Mahmod, M., et al.. (2021). Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine 31, 100683, https://doi.org/10.1016/j.eclinm.2020.100683.Search in Google Scholar
RKI (2021). Epidemiologischer Steckbrief zu SARS-CoV-2 und COVID-19. https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Steckbrief.html.Search in Google Scholar
Rueckert, L. and Levy, J. (1996). Further evidence that the callosum is involved in sustaining attention. Neuropsychologia 34, 927–935, https://doi.org/10.1016/0028-3932(96)00009-7.Search in Google Scholar
Schweinhardt, P. and Bushnell, M.C. (2010). Pain imaging in health and disease--how far have we come? J. Clin. Invest. 120, 3788–3797, https://doi.org/10.1172/jci43498.Search in Google Scholar
Simons, L.E., Elman, I., and Borsook, D. (2014). Psychological processing in chronic pain: A neural systems approach. Neurosci. Biobehav. Rev. 39, 61–78, https://doi.org/10.1016/j.neubiorev.2013.12.006.Search in Google Scholar
Skinner, J.E. and Yingling, C.D. (1977). Central gating mechanisms that regulate event-related potentials and behavior: A neural model for attention. Attention, Voluntary Contraction and Event-Related Cerebral Potentials. Progress in Clinical Neurophysiology. Desmedt, J.E., ed. (Karger), pp. 28–68.Search in Google Scholar
Sollini, M., Morbelli, S., Ciccarelli, M., Cecconi, M., Aghemo, A., Morelli, P., Chiola, S., Gelardi, F., and Chiti, A. (2021). Long COVID hallmarks on [18F]FDG-PET/CT: A case-control study. Eur. J. Nucl. Med. Mol. Imag. 48, 3187–3197, https://doi.org/10.1007/s00259-021-05294-3.Search in Google Scholar
Sonkaya, A.R., Öztrk, B., and Karadaş, Ö. (2021). Cerebral hemodynamic alterations in patients with Covid-19. Turk. J. Med. Sci. 51, 435–439, https://doi.org/10.3906/sag-2006-203.Search in Google Scholar
Staines, W.R., Graham, S.J., Black, S.E., and McIlroy, W.E. (2002). Task-relevant modulation of contralateral and ipsilateral primary somatosensory cortex and the role of a prefrontal-cortical sensory gating system. Neuroimage 15, 190–199, https://doi.org/10.1006/nimg.2001.0953.Search in Google Scholar
Tracey, I., Ploghaus, A., Gati, J.S., Clare, S., Smith, S., Menon, R.S., and Matthews, P.M. (2002). Imaging attentional modulation of pain in the periaqueductal gray in humans. J. Neurosci. 22, 2748–2752, https://doi.org/10.1523/jneurosci.22-07-02748.2002.Search in Google Scholar
Uddin, L.Q., Nomi, J.S., Hébert-Seropian, B., Ghaziri, J., and Boucher, O. (2017). Structure and function of the human insula. J. Clin. Neurophysiol. 34, 300–306, https://doi.org/10.1097/wnp.0000000000000377.Search in Google Scholar
Valet, M., Sprenger, T., Boecker, H., Willoch, F., Rummeny, E., Conrad, B., Erhard, P., and Tolle, T.R. (2004). Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain--an fMRI analysis. Pain 109, 399–408, https://doi.org/10.1016/j.pain.2004.02.033.Search in Google Scholar
Villemure, C. and Bushnell, C.M. (2002). Cognitive modulation of pain: How do attention and emotion influence pain processing? Pain 95, 195–199, https://doi.org/10.1016/s0304-3959(02)00007-6.Search in Google Scholar
Vlaeyen, J.W.S. and Linton, S.J. (2000). Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 85, 317–332, https://doi.org/10.1016/s0304-3959(99)00242-0.Search in Google Scholar
Wiech, K. and Tracey, I. (2009). The influence of negative emotions on pain: Behavioral effects and neural mechanisms. Neuroimage 47, 987–994, https://doi.org/10.1016/j.neuroimage.2009.05.059.Search in Google Scholar PubMed
Wierzba-Bobrowicz, T., Krajewski, P., Tarka, S., Acewicz, A., Felczak, P., Stępień, T., Golan, M.P., and Grzegorczyk, M. (2021). Neuropathological analysis of the brains of fifty-two patients with COVID-19. Folia Neuropathol. 59, 219–231, https://doi.org/10.5114/fn.2021.108829.Search in Google Scholar PubMed
Witelson, S.F. (1985). The brain connection: The corpus callosum is larger in left-handers. Science 229, 665–668, https://doi.org/10.1126/science.4023705.Search in Google Scholar PubMed
Yingling, C.D. and Skinner, J.E. (1977). Gating of thalamic input to cerebral cortex by nucleus reticularis thalami. Attention, Voluntary Contraction and Event-Related Cerebral Potentials. Progress in Clinical Neurophysiology. Desmedt, J.E., ed. (Karger), pp. 70–96.Search in Google Scholar
Zaidel, E. and Iacoboni, M. (2003). The parallel brain: The cognitive neuroscience of the corpus callosum (MIT Press: Cambridge, Massachusetts, London, England).10.7551/mitpress/5233.001.0001Search in Google Scholar
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