Journal of Neurology

, Volume 262, Issue 3, pp 729–741 | Cite as

Right mesial temporal lobe epilepsy impairs empathy-related brain responses to dynamic fearful faces

  • Gianina Toller
  • Babu Adhimoolam
  • Thomas Grunwald
  • Hans-Jürgen Huppertz
  • Martin Kurthen
  • Katherine P. Rankin
  • Hennric Jokeit
Original Communication

Abstract

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE on empathy-related brain responses in extra-amygdalar regions has not been investigated. Using functional magnetic resonance imaging, we measured empathy-related brain responses to dynamic fearful faces in 34 patients with unilateral MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy control group (n = 30). The primary finding was that right MTLE (RMTLE) was associated with decreased activity predominantly in the right amygdala and also in bilateral periaqueductal gray (PAG) but normal activity in the right anterior insula. The results of the extra-MTLE group demonstrate that these reduced amygdala and PAG responses go beyond the attenuation caused by antiepileptic and antidepressant medication. These findings clearly indicate that RMTLE affects the function of mesial temporal and midbrain structures that mediate basic interoceptive input necessary for the emotional awareness of empathic experiences of fear. Together with the decreased empathic concern found in the RMTLE group, this study provides neurobehavioral evidence that patients with RMTLE are at increased risk for reduced empathy towards others’ internal states and sheds new light on the nature of social-cognitive impairments frequently accompanying MTLE.

Keywords

Mesial temporal lobe epilepsy fMRI Fearful faces Empathy 

Supplementary material

415_2014_7622_MOESM1_ESM.pdf (71 kb)
Supplementary material 1 (PDF 71 kb)
415_2014_7622_MOESM2_ESM.pdf (186 kb)
Supplementary material 2 (PDF 187 kb)

References

  1. 1.
    Waxman SG, Geschwind N (1975) The interictal behavior syndrome of temporal lobe epilepsy. Arch Gen Psychiatry 32:1580–1586CrossRefPubMedGoogle Scholar
  2. 2.
    Bonora A, Benuzzi F, Monti G, Mirandola L, Pugnaghi M, Nichelli P, Meletti S (2011) Recognition of emotions from faces and voices in medial temporal lobe epilepsy. Epilepsy Behav 20:648–654CrossRefPubMedGoogle Scholar
  3. 3.
    Meletti S, Benuzzi F, Cantalupo G, Rubboli G, Tassinari CA, Nichelli P (2009) Facial emotion recognition impairment in chronic temporal lobe epilepsy. Epilepsia 50:1547–1559CrossRefPubMedGoogle Scholar
  4. 4.
    Broicher SD, Kuchukhidze G, Grunwald T, Krämer G, Kurthen M, Jokeit H (2012) “Tell me how do I feel”—Emotion recognition and theory of mind in symptomatic mesial temporal lobe epilepsy. Neuropsychologia 50:118–128CrossRefPubMedGoogle Scholar
  5. 5.
    Meletti S, Benuzzi F, Rubboli G, Cantalupo G, Stanzani Maserati M, Nichelli P, Tassinari CA (2003) Impaired facial emotion recognition in early-onset right mesial temporal lobe epilepsy. Neurology 60:426–431CrossRefPubMedGoogle Scholar
  6. 6.
    Giovagnoli AR, Franceschetti S, Reati F, Parente A, Maccagnano C, Villani F, Spreafico R (2011) Theory of mind in frontal and temporal lobe epilepsy: cognitive and neural aspects. Epilepsia 52:1995–2002CrossRefPubMedGoogle Scholar
  7. 7.
    Gu X, Gao Z, Wang X, Liu X, Knight RT, Hof PR, Fan J (2012) Anterior insular cortex is necessary for empathetic pain perception. Brain 135:2726–2735PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Preston SD, De Waal F (2002) Empathy: its ultimate and proximate bases. Behav Brain Sci 25:1–20PubMedGoogle Scholar
  9. 9.
    Eisenberg N, Strayer J (1990) Empathy and its development. Cambridge University Press, CambridgeGoogle Scholar
  10. 10.
    Decety J, Lamm C (2006) Human empathy through the lens of social neuroscience. Scientific World Journal 6:1146–1163CrossRefPubMedGoogle Scholar
  11. 11.
    Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD (2004) Empathy for pain involves the affective but not sensory components of pain. Science 303:1157–1162CrossRefPubMedGoogle Scholar
  12. 12.
    Singer T (2006) The neuronal basis and ontogeny of empathy and mind reading: review of literature and implications for future research. Neurosci Biobehav Rev 30:855–863CrossRefPubMedGoogle Scholar
  13. 13.
    Shamay-Tsoory SG (2011) The neural bases for empathy. Neuroscientist 17:18–24CrossRefPubMedGoogle Scholar
  14. 14.
    Shamay-Tsoory SG, Lester H, Chisin R, Israel O, Bar-Shalom R, Peretz A, Tomer R, Tsitrinbaum Z, Aharon-Peretz J (2005) The neural correlates of understanding the other’s distress: a positron emission tomography investigation of accurate empathy. Neuroimage 27:468–472CrossRefPubMedGoogle Scholar
  15. 15.
    Lamm C, Decety J, Singer T (2011) Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. Neuroimage 54:2492–2502CrossRefPubMedGoogle Scholar
  16. 16.
    Saarela MV, Hlushchuk Y, Williams ACdC, Schürmann M, Kalso E, Hari R (2007) The compassionate brain: humans detect intensity of pain from another’s face. Cereb Cortex 17:230–237CrossRefPubMedGoogle Scholar
  17. 17.
    Wicker B, Keysers C, Plailly J, Royet J-P, Gallese V, Rizzolatti G (2003) Both of us disgusted in my insula: the common neural basis of seeing and feeling disgust. Neuron 40:655–664CrossRefPubMedGoogle Scholar
  18. 18.
    Schacher M, Winkler R, Grunwald T, Kraemer G, Kurthen M, Reed V, Jokeit H (2006) Mesial temporal lobe epilepsy impairs advanced social cognition. Epilepsia 47:2141–2146CrossRefPubMedGoogle Scholar
  19. 19.
    De Gelder B, Snyder J, Greve D, Gerard G, Hadjikhani N (2004) Fear fosters flight: a mechanism for fear contagion when perceiving emotion expressed by a whole body. Proc Natl Acad Sci USA 101:16701–16706PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Craig AD (2002) How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3:655–666CrossRefPubMedGoogle Scholar
  21. 21.
    Craig AD (2009) How do you feel—now? The anterior insula and human awareness. Nat Rev Neurosci 10:59–70CrossRefPubMedGoogle Scholar
  22. 22.
    Critchley HD, Wiens S, Rotshtein P, Öhman A, Dolan RJ (2004) Neural systems supporting interoceptive awareness. Nat Neurosci 7:189–195CrossRefPubMedGoogle Scholar
  23. 23.
    Singer T, Critchley HD, Preuschoff K (2009) A common role of insula in feelings, empathy and uncertainty. Trends Cogn Sci 13:334–340CrossRefPubMedGoogle Scholar
  24. 24.
    Leigh R, Oishi K, Hsu J, Lindquist M, Gottesman RF, Jarso S, Crainiceanu C, Mori S, Hillis AE (2013) Acute lesions that impair affective empathy. Brain 136:2539–2549PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Fan Y, Duncan NW, de Greck M, Northoff G (2011) Is there a core neural network in empathy? An fMRI based quantitative meta-analysis. Neurosci Biobehav Rev 35:903–911CrossRefPubMedGoogle Scholar
  26. 26.
    Craig AD (2005) Forebrain emotional asymmetry: a neuroanatomical basis? Trends Cogn Sci 9:566–571CrossRefPubMedGoogle Scholar
  27. 27.
    Adolphs R, Tranel D, Damasio H, Damasio A (1994) Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 372:669–672CrossRefPubMedGoogle Scholar
  28. 28.
    Adolphs R, Tranel D, Hamann S, Young AW, Calder AJ, Phelps EA, Anderson A, Lee G, Damasio AR (1999) Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia 37:1111–1117CrossRefPubMedGoogle Scholar
  29. 29.
    LeDoux JE (1996) The emotional brain. Simon and Schuster, New YorkGoogle Scholar
  30. 30.
    Morris JS, Frith CD, Perrett DI, Rowland D, Young AW, Calder AJ, Dolan RJ (1996) A differential neural response in the human amygdala to fearful and happy facial expressions. Nature 383:812–815CrossRefPubMedGoogle Scholar
  31. 31.
    Breiter HC, Etcoff NL, Whalen PJ, Kennedy WA, Rauch SL, Buckner RL, Strauss MM, Hyman SE, Rosen BR (1996) Response and habituation of the human amygdala during visual processing of facial expression. Neuron 17:875–887CrossRefPubMedGoogle Scholar
  32. 32.
    Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26:321–352CrossRefPubMedGoogle Scholar
  33. 33.
    Price JL (1999) Prefrontal cortical networks related to visceral function and mood. Ann NY Acad Sci 877:383–396CrossRefPubMedGoogle Scholar
  34. 34.
    Davis M (1992) The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15:353–375CrossRefPubMedGoogle Scholar
  35. 35.
    Mobbs D, Marchant JL, Hassabis D, Seymour B, Tan G, Gray M, Petrovic P, Dolan RJ, Frith CD (2009) From threat to fear: the neural organization of defensive fear systems in humans. J Neurosci 29:12236–12243PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Mobbs D, Yu R, Rowe JB, Eich H, FeldmanHall O, Dalgleish T (2010) Neural activity associated with monitoring the oscillating threat value of a tarantula. Proc Natl Acad Sci USA 107:20582–20586PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Schacher M, Haemmerle B, Woermann FG, Okujava M, Huber D, Grunwald T, Kramer G, Jokeit H (2006) Amygdala fMRI lateralizes temporal lobe epilepsy. Neurology 66:81–87CrossRefPubMedGoogle Scholar
  38. 38.
    Broicher SD, Frings L, Huppertz HJ, Grunwald T, Kurthen M, Kramer G, Jokeit H (2012) Alterations in functional connectivity of the amygdala in unilateral mesial temporal lobe epilepsy. J Neurol 259:2546–2554CrossRefPubMedGoogle Scholar
  39. 39.
    Labudda K, Mertens M, Steinkroeger C, Bien CG, Woermann FG (2013) Lesion side matters—an fMRI study on the association between neural correlates of watching dynamic fearful faces and their evaluation in patients with temporal lobe epilepsy. Epilepsy Behav 31:321–328CrossRefPubMedGoogle Scholar
  40. 40.
    Batut AC, Gounot D, Namer IJ, Hirsch E, Kehrli P, Metz-Lutz MN (2006) Neural responses associated with positive and negative emotion processing in patients with left versus right temporal lobe epilepsy. Epilepsy Behav 9:415–423CrossRefPubMedGoogle Scholar
  41. 41.
    Benuzzi F, Meletti S, Zamboni G, Calandra-Buonaura G, Serafini M, Lui F, Baraldi P, Rubboli G, Tassinari CA, Nichelli P (2004) Impaired fear processing in right mesial temporal sclerosis: a fMRI study. Brain Res Bull 63:269–281CrossRefPubMedGoogle Scholar
  42. 42.
    Bonelli SB, Powell R, Yogarajah M, Thompson PJ, Symms MR, Koepp MJ, Duncan JS (2009) Preoperative amygdala fMRI in temporal lobe epilepsy. Epilepsia 50:217–227PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Adolphs R, Damasio H, Tranel D, Damasio AR (1996) Cortical systems for the recognition of emotion in facial expressions. J Neurosci 16:7678–7687PubMedGoogle Scholar
  44. 44.
    Borod JC, Cicero BA, Obler LK, Welkowitz J, Erhan HM, Santschi C, Grunwald IS, Agosti RM, Whalen JR (1998) Right hemisphere emotional perception: evidence across multiple channels. Neuropsychology 12:446–458CrossRefPubMedGoogle Scholar
  45. 45.
    Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27:2349–2356PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Tomasi D, Volkow ND (2011) Association between functional connectivity hubs and brain networks. Cereb Cortex 21:2003–2013PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Jokeit H, Okujava M, Woermann FG (2001) Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study. BMC Neurol 1:6PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Kida I, Smith AJ, Blumenfeld H, Behar KL, Hyder F (2006) Lamotrigine suppresses neurophysiological responses to somatosensory stimulation in the rodent. Neuroimage 29:216–224CrossRefPubMedGoogle Scholar
  49. 49.
    Windischberger C, Lanzenberger R, Holik A, Spindelegger C, Stein P, Moser U, Gerstl F, Fink M, Moser E, Kasper S (2010) Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study. Neuroimage 49:1161–1170CrossRefPubMedGoogle Scholar
  50. 50.
    Kanner AM, Schachter SC, Barry JJ, Hersdorffer DC, Mula M, Trimble M, Hermann B, Ettinger AE, Dunn D, Caplan R, Ryvlin P, Gilliam F (2012) Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence. Epilepsy Behav 24:156–168CrossRefPubMedGoogle Scholar
  51. 51.
    Paulus C (2009) Der Saarbrücker Persönlichkeitsfragebogen SPF (IRI) zur Messung von Empathie: Psychometrische Evaluation der deutschen Version des Interpersonal Reactivity Index. http://psydok.sulb.uni-saarland.de/volltexte/2009/2363/
  52. 52.
    Davis MH (1983) Measuring individual differences in empathy: evidence for a multidimenstional approach. J Pers Soc Psychol 44:113–126CrossRefGoogle Scholar
  53. 53.
    Benjamini Y, Yekutieli D (2001) The control of the false discovery rate in multiple testing under dependency. Ann Stat 29:1165–1188CrossRefGoogle Scholar
  54. 54.
    Friston KJ, Ashburner JT, Kiebel SJ, Nichols TE, Penny WD (2007) Statistical parametric mapping: the analysis of functional brain images. Academic Press, LondonCrossRefGoogle Scholar
  55. 55.
    Mather M (2012) The emotion paradox in the aging brain. Ann NY Acad Sci 1251:33–49PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    St Jacques PL, Bessette-Symons B, Cabeza R (2009) Functional neuroimaging studies of aging and emotion: fronto-amygdalar differences during emotional perception and episodic memory. J Int Neuropsychol Soc 15:819–825PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Brett M, Anton J-L, Valabregue R, Poline J-B (2002) Region of interest analysis using the MarsBar toolbox for SPM 99. Neuroimage 16:497Google Scholar
  58. 58.
    Gallese V (2001) The ‘shared manifold’ hypothesis. From mirror neurons to empathy. J Conscious Stud 8:5–7Google Scholar
  59. 59.
    McClelland S 3rd, Garcia RE, Peraza DM, Shih TT, Hirsch LJ, Hirsch J, Goodman RR (2006) Facial emotion recognition after curative nondominant temporal lobectomy in patients with mesial temporal sclerosis. Epilepsia 47:1337–1342CrossRefPubMedGoogle Scholar
  60. 60.
    Hlobil U, Rathore C, Alexander A, Sarma S, Radhakrishnan K (2008) Impaired facial emotion recognition in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS): side and age at onset matters. Epilepsy Res 80:150–157CrossRefPubMedGoogle Scholar
  61. 61.
    Sedda A, Rivolta D, Scarpa P, Burt M, Frigerio E, Zanardi G, Piazzini A, Turner K, Canevini MP, Francione S, Lo Russo G, Bottini G (2013) Ambiguous emotion recognition in temporal lobe epilepsy: the role of expression intensity. Cogn Affect Behav Neurosci 13:452–463CrossRefPubMedGoogle Scholar
  62. 62.
    Hillis AE (2013) Inability to empathize: brain lesions that disrupt sharing and understanding another’s emotions. Brain 137:981–997PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Lamm C, Batson CD, Decety J (2007) The neural substrate of human empathy: effects of perspective-taking and cognitive appraisal. J Cogn Neurosci 19:42–58CrossRefPubMedGoogle Scholar
  64. 64.
    Ansakorpi H, Korpelainen JT, Huikuri HV, Tolonen U, Myllyla VV, Isojarvi JI (2002) Heart rate dynamics in refractory and well controlled temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 72:26–30PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Druschky A, Hilz MJ, Hopp P, Platsch G, Radespiel-Troger M, Druschky K, Kuwert T, Stefan H, Neundorfer B (2001) Interictal cardiac autonomic dysfunction in temporal lobe epilepsy demonstrated by [(123)I]metaiodobenzylguanidine-SPECT. Brain 124:2372–2382CrossRefPubMedGoogle Scholar
  66. 66.
    Craig AD (2003) Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 13:500–505CrossRefPubMedGoogle Scholar
  67. 67.
    Rankin KP, Gorno-Tempini ML, Allison SC, Stanley CM, Glenn S, Weiner MW, Miller BL (2006) Structural anatomy of empathy in neurodegenerative disease. Brain 129:2945–2956PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Sturm VE, Yokoyama JS, Seeley WW, Kramer JH, Miller BL, Rankin KP (2013) Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration. Proc Natl Acad Sci USA 110:9944–9949PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    Sherman E, Griffiths SY, Akdag S, Connolly MB, Slick DJ, Wiebe S (2008) Sociodemographic correlates of health-related quality of life in pediatric epilepsy. Epilepsy Behav 12:96–101CrossRefPubMedGoogle Scholar
  70. 70.
    Woermann FG, Jokeit H, Luerding R, Freitag H, Schulz R, Guertler S, Okujava M, Wolf P, Tuxhorn I, Ebner A (2003) Language lateralization by Wada test and fMRI in 100 patients with epilepsy. Neurology 61:699–701CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Gianina Toller
    • 1
  • Babu Adhimoolam
    • 2
  • Thomas Grunwald
    • 1
  • Hans-Jürgen Huppertz
    • 1
  • Martin Kurthen
    • 1
  • Katherine P. Rankin
    • 2
  • Hennric Jokeit
    • 1
  1. 1.Swiss Epilepsy CenterZurichSwitzerland
  2. 2.Memory and Aging Center, Department of NeurologyUniversity of CaliforniaSan FranciscoUSA

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