Skip to main content
SpringerLink
Log in

Dysconnectivity in Hallucinations

  • Chapter
  • First Online:
Hallucinations in Psychoses and Affective Disorders

  • 710 Accesses

Abstract

Abnormalities in brain connectivity are associated with hallucinations. Several networks including sensory and resting-state networks have been pointed out as crucial in various hallucination modalities. Here we review the literature on brain connectivity relevant to auditory verbal and visual hallucinations with an emphasis on the most recent studies. Most recent literature investigates this issue in first-episode patients who are mainly medication naive. This enables the investigation of “true” abnormalities in brain connections, how they change with medication, and how they develop with illness progression. The literature that includes neural correlates of hallucinations in mood disorder is deficient. Both visual and auditory verbal hallucinations are associated with abnormal connections of perception areas, specific to that particular hallucination modality.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Geoffroy PA, Houenou J, Duhamel A, Amad A, De Weijer AD, Curcic-Blake B, Linden DE, Thomas P, Jardri R. The arcuate fasciculus in auditory-verbal hallucinations: a meta-analysis of diffusion-tensor-imaging studies. Schizophr Res. 2014;159:234.

    Article  Google Scholar 

  2. Alderson-Day B, Diederen K, Fernyhough C, Ford JM, Horga G, Margulies DS, McCarthy- Jones S, Northoff G, Shine JM, Turner J, van de Ven V, van Lutterveld R, Waters F, Jardri R. Auditory hallucinations and the Brain’s Resting-State Networks: findings and methodological observations. Schizophr Bull. 2016;42:1110.

    Article  Google Scholar 

  3. Alderson-Day B, McCarthy-Jones S, Fernyhough C. Hearing voices in the resting brain: a review of intrinsic functional connectivity research on auditory verbal hallucinations. Neurosci Biobehav Rev. 2015;55:78–87.

    Article  Google Scholar 

  4. Čurčic-Blake B, Ford J, Hubl D, Orlov ND, Sommer IE, Waters F, Allen P, Jardri R, Woodruff PW, Olivier D, Mulert C, Woodward TS, Aleman A. Interaction of language, auditory and memory brain networks in auditory verbal hallucinations. Prog Neurobiol. 2017;148:1–20.

    Article  Google Scholar 

  5. Rieger K, Diaz Hernandez L, Baenninger A, Koenig T. 15 years of microstate research in schizophrenia—where are we? A meta-analysis. Front Psych. 2016;7:22.

    Google Scholar 

  6. Steinmann S, Leicht G, Mulert C. Interhemispheric auditory connectivity: structure and function related to auditory verbal hallucinations. Front Hum Neurosci. 2014;8:55.

    Article  Google Scholar 

  7. Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull. 2009;35:509–27.

    Article  Google Scholar 

  8. Stephan KE, Baldeweg T, Friston KJ. Synaptic plasticity and dysconnection in schizophrenia. Biol Psychiatry. 2006;59:929–39.

    Article  CAS  Google Scholar 

  9. Hubl D, Koenig T, Strik W, Federspiel A, Kreis R, Boesch C, Maier SE, Schroth G, Lovblad K, Dierks T. Pathways that make voices: white matter changes in auditory hallucinations. Arch Gen Psychiatry. 2004;61:658–68.

    Article  Google Scholar 

  10. Shergill SS, Kanaan RA, Chitnis XA, O'Daly O, Jones DK, Frangou S, Williams SC, Howard RJ, Barker GJ, Murray RM, McGuire P. A diffusion tensor imaging study of fasciculi in schizophrenia. Am J Psychiatry. 2007;164:467–73.

    Article  Google Scholar 

  11. Rotarska-Jagiela A, Oertel-Knoechel V, DeMartino F, van de Ven V, Formisano E, Roebroeck A, Rami A, Schoenmeyer R, Haenschel C, Hendler T, Maurer K, Vogeley K, Linden DE. Anatomical brain connectivity and positive symptoms of schizophrenia: a diffusion tensor imaging study. Psychiatry Res. 2009;174:9–16.

    Article  Google Scholar 

  12. Knochel C, O'Dwyer L, Alves G, Reinke B, Magerkurth J, Rotarska-Jagiela A, Prvulovic D, Hampel H, Linden DEJ, Oertel-Knochel V. Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives. Schizophr Res. 2012;140:129–35.

    Article  Google Scholar 

  13. Seok JH, Park HJ, Chun JW, Lee SK, Cho HS, Kwon JS, Kim JJ. White matter abnormalities associated with auditory hallucinations in schizophrenia: a combined study of voxel- based analyses of diffusion tensor imaging and structural magnetic resonance imaging. Psychiatry Res. 2007;156:93–104.

    Article  Google Scholar 

  14. Čurčic-Blake B, Nanetti L, van der Meer L, Cerliani L, Renken R, Pijnenborg GH, Aleman A. Not on speaking terms: hallucinations and structural network dysconnectivity in schizophrenia. Brain Struct Funct. 2015;220:407–18.

    Article  Google Scholar 

  15. McCarthy-Jones S, Oestreich LK, Whitford TJ, Australian Schizophrenia Research Bank. Reduced integrity of the left arcuate fasciculus is specifically associated with auditory verbal hallucinations in schizophrenia. Schizophr Res. 2015;162:1–6.

    Article  Google Scholar 

  16. Abdul-Rahman MF, Qiu A, Woon PS, Kuswanto C, Collinson SL, Sim K. Arcuate fasciculus abnormalities and their relationship with psychotic symptoms in schizophrenia. PLoS One. 2012;7:e29315.

    Article  CAS  Google Scholar 

  17. van Tol M, van dM, Bruggeman R, Modinos G, Knegtering H, Aleman A. Voxel-based gray and white matter morphometry correlates of hallucinations in schizophrenia: the superior temporal gyrus does not stand alone()(). NeuroImage Clin. 2013;4:249–57.

    PubMed  PubMed Central  Google Scholar 

  18. Whitford TJ, Lee SW, Oh JS, de Luis-Garcia R, Savadjiev P, Alvarado JL, Westin CF, Niznikiewicz M, Nestor PG, McCarley RW, Kubicki M, Shenton ME. Localized abnormalities in the cingulum bundle in patients with schizophrenia: a Diffusion Tensor tractography study. Neuroimage Clin. 2014;5:93–9.

    Article  Google Scholar 

  19. Mulert C, Kirsch V, Whitford TJ, Alvarado J, Pelavin P, McCarley RW, Kubicki M, Salisbury DF, Shenton ME. Hearing voices: a role of interhemispheric auditory connectivity? World J Biol Psychiatry. 2012;13:153–8.

    Article  Google Scholar 

  20. Wigand M, Kubicki M, Clemm von Hohenberg C, Leicht G, Karch S, Eckbo R, Pelavin PE, Hawley K, Rujescu D, Bouix S, Shenton ME, Mulert C. Auditory verbal hallucinations and the interhemispheric auditory pathway in chronic schizophrenia. World J Biol Psychiatry. 2015;16:31–44.

    Article  Google Scholar 

  21. Oestreich LK, McCarthy-Jones S, Whitford TJ, Australian Schizophrenia Research Bank. Decreased integrity of the fronto-temporal fibers of the left inferior occipito-frontal fasciculus associated with auditory verbal hallucinations in schizophrenia. Brain Imaging Behav. 2016;10(2):445–54.

    Article  Google Scholar 

  22. Bopp MHA, Zollner R, Jansen A, Dietsche B, Krug A, Kircher TTJ. White matter integrity and symptom dimensions of schizophrenia: a diffusion tensor imaging study. Schizophr Res. 2017;184:59–68.

    Article  Google Scholar 

  23. Von Der Heide RJ, Skipper LM, Klobusicky E, Olson IR. Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis. Brain. 2013;136:1692–707.

    Article  Google Scholar 

  24. Amico F, O’Hanlon E, Kraft D, Oertel-Knochel V, Clarke M, Kelleher I, Higgins N, Coughlan H, Creegan D, Heneghan M, Power E, Power L, Ryan J, Frodl T, Cannon M. Functional connectivity anomalies in adolescents with psychotic symptoms. PLoS One. 2017;12:e0169364.

    Google Scholar 

  25. Zheng L, Liu W, He W, Yu S, Zhong G. Altered effective brain connectivity at early response of antipsychotics in first-episode schizophrenia with auditory hallucinations. Clin Neurophysiol. 2017;128:867–74.

    Article  Google Scholar 

  26. Chang X, Collin G, Xi Y, Cui L, Scholtens LH, Sommer IE, Wang H, Yin H, Kahn RS, van den Heuvel MP. Resting-state functional connectivity in medication-naive schizophrenia patients with and without auditory verbal hallucinations: a preliminary report. Schizophr Res. 2017;188:75.

    Article  Google Scholar 

  27. Li B, Cui LB, Xi YB, Friston KJ, Guo F, Wang HN, Zhang LC, Bai YH, Tan QR, Yin H, Lu H. Abnormal effective connectivity in the brain is involved in auditory verbal hallucinations in schizophrenia. Neurosci Bull. 2017;33(3):281–91.

    Article  Google Scholar 

  28. Neves M d C, Duarte DG, Albuquerque MR, Nicolato R, Neves FS, de Souza-Duran FL, Busatto G, Corrêa H. Neural correlates of hallucinations in bipolar disorder. Revista Brasileira de Psiquiatria. 2016;38(1):1–5.

    Article  Google Scholar 

  29. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for affective disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL): initial reliability and validity data. J Am Acad Child Adoles Psychiat. 1997;36(7):980–8.

    Article  CAS  Google Scholar 

  30. Cui LB, Liu K, Li C, Wang LX, Guo F, Tian P, Wu YJ, Guo L, Liu WM, Xi YB, Wang HN, Yin H. Putamen-related regional and network functional deficits in first-episode schizophrenia with auditory verbal hallucinations. Schizophr Res. 2016;173:13–22.

    Article  Google Scholar 

  31. Shinn AK, Baker JT, Cohen BM, Ongur D. Functional connectivity of left Heschl’s gyrus in vulnerability to auditory hallucinations in schizophrenia. Schizophr Res. 2013;143:260–8.

    Article  Google Scholar 

  32. Sommer IE, Clos M, Meijering AL, Diederen KM, Eickhoff SB. Resting state functional connectivity in patients with chronic hallucinations. PLoS One. 2012;7:e43516.

    Article  CAS  Google Scholar 

  33. Alonso-Solis A, Vives-Gilabert Y, Grasa E, Portella MJ, Rabella M, Sauras RB, Roldan A, Nunez-Marin F, Gomez-Anson B, Perez V, Alvarez E, Corripio I. Resting-state functional connectivity alterations in the default network of schizophrenia patients with persistent auditory verbal hallucinations. Schizophr Res. 2015;161:261–8.

    Article  Google Scholar 

  34. van Lutterveld R, Diederen KM, Otte WM, Sommer IE. Network analysis of auditory hallucinations in nonpsychotic individuals. Hum Brain Mapp. 2014;35:1436–45.

    Article  Google Scholar 

  35. Kindler J, Jann K, Homan P, Hauf M, Walther S, Strik W, Dierks T, Hubl D. Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia. Schizophr Bull. 2013;41:163–70.

    Article  Google Scholar 

  36. Northoff G, Qin P. How can the brain’s resting state activity generate hallucinations? A ‘resting state hypothesis’ of auditory verbal hallucinations. Schizophr Res. 2011;127:202–14.

    Article  Google Scholar 

  37. Jardri R, Pouchet A, Pins D, Thomas P. Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. Am J Psychiatry. 2011;168:73–81.

    Article  Google Scholar 

  38. Kompus K, Westerhausen R, Hugdahl K. The “paradoxical” engagement of the primary auditory cortex in patients with auditory verbal hallucinations: a meta-analysis of functional neuroimaging studies. Neuropsychologia. 2011;49:3361–9.

    Article  Google Scholar 

  39. Kuhn S, Gallinat J. Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia. Schizophr Bull. 2010;32:358–65.

    Google Scholar 

  40. Friston KJ, Harrison L, Penny W. Dynamic causal modeling. NeuroImage. 2003;19:1273–302.

    Article  CAS  Google Scholar 

  41. Čurčic-Blake B, Liemburg E, Vercammen A, Swart M, Knegtering H, Bruggeman R, Aleman A. When Broca goes uninformed: reduced information flow to Broca’s area in schizophrenia patients with auditory hallucinations. Schizophr Bull. 2013;39:1087–95.

    Article  Google Scholar 

  42. Lefebvre S, Demeulemeester M, Leroy A, Delmaire C, Lopes R, Pins D, Thomas P, Jardri R. Network dynamics during the different stages of hallucinations in schizophrenia. Hum Brain Mapp. 2016;37:2571–86.

    Article  Google Scholar 

  43. Raij TT, Valkonen-Korhonen M, Holi M, Therman S, Lehtonen J, Hari R. Reality of auditory verbal hallucinations. Brain. 2009;132:2994–3001.

    Article  Google Scholar 

  44. Hoffman RE, Fernandez T, Pittman B, Hampson M. Elevated functional connectivity along a corticostriatal loop and the mechanism of auditory/verbal hallucinations in patients with schizophrenia. Biol Psychiatry. 2011;69:407–14.

    Article  Google Scholar 

  45. Thoma RJ, Chaze C, Lewine JD, Calhoun VD, Clark VP, Bustillo J, Houck J, Ford J, Bigelow R, Wilhelmi C, Stephen JM, Turner JA. Functional MRI evaluation of multiple neural networks underlying auditory verbal hallucinations in schizophrenia spectrum disorders. Front Psych. 2016;7:39.

    Google Scholar 

  46. Sritharan A, Line P, Sergejew A, Silberstein R, Egan G, Copolov D. EEG coherence measures during auditory hallucinations in schizophrenia. Psychiatry Res. 2005;136:189–200.

    Article  Google Scholar 

  47. Angelopoulos E, Koutsoukos E, Maillis A, Papadimitriou GN, Stefanis C. Cortical interactions during the experience of auditory verbal hallucinations. J Neuropsychiatry Clin Neurosci. 2011;23:287–93.

    Article  Google Scholar 

  48. Koutsoukos E, Angelopoulos E, Maillis A, Papadimitriou GN, Stefanis C. Indication of increased phase coupling between theta and gamma EEG rhythms associated with the experience of auditory verbal hallucinations. Neurosci Lett. 2013;534:242–5.

    Article  CAS  Google Scholar 

  49. Kindler J, Hubl D, Strik WK, Dierks T, Koenig T. Resting-state EEG in schizophrenia: auditory verbal hallucinations are related to shortening of specific microstates. Clin Neurophysiol. 2011;122:1179–82.

    Article  CAS  Google Scholar 

  50. Mechelli A, Allen P, Amaro E, Fu CHY, Williams SCR, Brammer MJ, Johns LC, McGuire PK. Misattribution of speech and impaired connectivity in patients with auditory verbal hallucinations. Hum Brain Mapp. 2007;28:1213–22.

    Article  Google Scholar 

  51. Hozer F, Houenou J. Can neuroimaging disentangle bipolar disorder? J Affect Disord. 2016;195:199–214.

    Article  Google Scholar 

  52. Collerton D, Mosimann UP, Perry E. The neuroscience of visual hallucinations. Oxford: John Wiley & Sons; 2015.

    Google Scholar 

  53. Waters F, Collerton D, Ffytche DH, Jardri R, Pins D, Dudley R, Blom JD, Mosimann UP, Eperjesi F, Ford S, Laroi F. Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease. Schizophr Bull. 2014;40(Suppl. 4):S233–45.

    Article  Google Scholar 

  54. Jardri R, Thomas P, Delmaire C, Delion P, Pins D. The neurodynamic organization of modality-dependent hallucinations. Cereb Cortex. 2013;23:1108–17.

    Article  Google Scholar 

  55. Ford JM, Palzes VA, Roach BJ, Potkin SG, van Erp TG, Turner JA, Mueller BA, Calhoun VD, Voyvodic J, Belger A, Bustillo J, Vaidya JG, Preda A, McEwen SC, Mathalon DH, Functional Imaging Biomedical Informatics Research Network. Visual hallucinations are associated with hyperconnectivity between the amygdala and visual cortex in people with a diagnosis of schizophrenia. Schizophr Bull. 2015;41:223–32.

    Article  Google Scholar 

  56. Amad A, Cachia A, Gorwood P, Pins D, Delmaire C, Rolland B, Mondino M, Thomas P, Jardri R. The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations. Mol Psychiatry. 2014;19:184–91.

    Article  CAS  Google Scholar 

  57. Hare SM, Ford JM, Ahmadi A, Damaraju E, Belger A, Bustillo J, Lee HJ, Mathalon DH, Mueller BA, Preda A, van Erp Theo GM, Potkin SG, Calhoun VD, Turner JA. Modality-dependent impact of hallucinations on low-frequency fluctuations in schizophrenia. Schizophr Bull. 2017;43:389–96.

    Article  Google Scholar 

  58. Rolland B, Amad A, Poulet E, Bordet R, Vignaud A, Bation R, Delmaire C, Thomas P, Cottencin O, Jardri R. Resting-state functional connectivity of the nucleus accumbens in auditory and visual hallucinations in schizophrenia. Schizophr Bull. 2015;41:291–9.

    Article  Google Scholar 

  59. Yao N, Pang S, Cheung C, Chang RS, Lau KK, Suckling J, Yu K, Mak HK, McAlonan G, Ho SL, Chua SE. Resting activity in visual and corticostriatal pathways in Parkinson’s disease with hallucinations. Parkinsonism Relat Disord. 2015;21:131–7.

    Article  Google Scholar 

  60. Yao N, Shek-Kwan Chang R, Cheung C, Pang S, Lau KK, Suckling J, Rowe JB, Yu K, Ka-Fung Mak H, Chua SE, Ho SL, McAlonan GM. The default mode network is disrupted in Parkinson’s disease with visual hallucinations. Hum Brain Mapp. 2014;35:5658–66.

    Article  Google Scholar 

  61. Franciotti R, Delli Pizzi S, Perfetti B, Tartaro A, Bonanni L, Thomas A, Weis L, Biundo R, Antonini A, Onofrj M. Default mode network links to visual hallucinations: a comparison between Parkinson’s disease and multiple system atrophy. Mov Disord. 2015;30:1237–47.

    Article  Google Scholar 

  62. Yao N, Cheung C, Pang S, Shek-kwan Chang R, Lau KK, Suckling J, Yu K, Ka-Fung Mak H, Chua SE, Ho SL, McAlonan GM. Multimodal MRI of the hippocampus in Parkinson’s disease with visual hallucinations. Brain Struct Funct. 2016;221:287–300.

    Article  Google Scholar 

  63. Shine JM, Muller AJ, O’Callaghan C, Hornberger M, Halliday GM, Lewis SJG. Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson’s disease: a task-based fMRI study. NPJ Parkinson’s Disease. 2015;1. Article number 15003.

    Google Scholar 

  64. Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 2012;109:2138–43.

    Article  Google Scholar 

  65. Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, Tagliazucchi E, Schenberg EE, Nest T, Orban C, Leech R, Williams LT, Williams TM, Bolstridge M, Sessa B, McGonigle J, Sereno MI, Nichols D, Hellyer PJ, Hobden P, Evans J, Singh KD, Wise RG, Curran HV, Feilding A, Nutt DJ. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc Natl Acad Sci U S A. 2016;113:4853–8.

    Article  CAS  Google Scholar 

  66. Roseman L, Sereno MI, Leech R, Kaelen M, Orban C, McGonigle J, Feilding A, Nutt DJ, Carhart-Harris RL. LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion. Hum Brain Mapp. 2016;37:3031–40.

    Article  Google Scholar 

  67. Behrendt R. Contribution of hippocampal region CA3 to consciousness and schizophrenic hallucinations. Neurosci Biobehav Rev. 2010;34:1121–36.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

    Branislava Ćurčić-Blake

  2. APHP, Hôpitaux Univ. Mondor, DHU PePsy, Pôle de psychiatry, Faculty of Medicine, Université Paris Est Créteil, Créteil, France

    Josselin Houenou

  3. INSERM U955 Equipe 15 “Psychiatrie Translationnelle”, Fondation FondaMental, Créteil, France

    Josselin Houenou

  4. NeuroSpin Neuroimaging Platform, UNIACT Lab, Psychiatry Team, CEA Saclay, Gif Sur Yvette, France

    Josselin Houenou

  5. Univ Lille, SCALab, CNRS UMR-9193 and School of Medicine, Lille, France

    Renaud Jardri

  6. CHU Lille, Fontan Hospital, CURE Platform, Lille, France

    Renaud Jardri

Authors
  1. Branislava Ćurčić-Blake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josselin Houenou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renaud Jardri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Branislava Ćurčić-Blake .

Editor information

Editors and Affiliations

  1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    Paolo Brambilla

  2. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    Massimo Carlo Mauri

  3. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    Alfredo Carlo Altamura

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ćurčić-Blake, B., Houenou, J., Jardri, R. (2018). Dysconnectivity in Hallucinations. In: Brambilla, P., Mauri, M., Altamura, A. (eds) Hallucinations in Psychoses and Affective Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-75124-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-75124-5_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-75123-8

  • Online ISBN: 978-3-319-75124-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation