Auditory Hallucinations as Translational Psychiatry: Evidence from Magnetic Resonance Imaging

In this invited review article, I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway, with a focus on the neuronal mechanisms underlying the phenomenology of experiencing “hearing voices”. An auditory verbal hallucination (i.e. hearing a voice) is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations, called Levels of Explanation. Using a Levels of Explanation approach, mental phenomena can be described and explained at different levels (cultural, clinical, cognitive, brainimaging, cellular and molecular). Another way of saying this is that, to advance knowledge in a research field, it is not only necessary to replicate findings, but also to show how evidence obtained with one method, and at one level of explanation, converges with evidence obtained with another method at another level. To achieve breakthroughs in our understanding of auditory verbal hallucinations, we have to advance vertically through the various levels, rather than the more common approach of staying at our favourite level and advancing horizontally (e.g., more advanced techniques and datacquisition analyses). The horizontal expansion will, however, not advance a deeper understanding of how an auditory verbal hallucination spontaneously starts and stops. Finally, I present data from the clinical, cognitive, brain-imaging, and cellular levels, where data from one level validate and support data at another level, called converging of evidence. Using a translational approach, the current status of auditory verbal hallucinations is that they implicate speech perception areas in the left temporal lobe, impairing perception of and attention to external sounds. Preliminary results also show that amygdala is implicated in the emotional «colouring» of the voices and that excitatory neurotransmitters might be involved. What we do not know is why hallucinatory episodes occur spontaneously, why they fluctuate over time, and what makes them spontaneously stop. Moreover, is voice hearing a category or dimension in its own right, independent of diagnosis, and why is the auditory modality predominantly implicated in psychotic disorders, while the visual modality dominates in, for example, neurological diseases?

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1. Hugdahl K, Sommer IE. Auditory Verbal Hallucinations in Schizophrenia from a Levels of Explanation Perspective. Schizophr Bull 2017.
2. Johns LC, Kompus K, Connell W, Humpston C, Lincoln TW, Longden E, et al. Auditory verbal hallucinations in persons with and without a need for care. Schizophr Bull 2013;40(Suppl 4):255-64.
3. Larøi F, Aleman A. Hallucinations - A guide to treatment and management. Oxford, UK: Oxford University Press; 2010.
4. Kråkvik B, Stiles T, Hugdahl K. Experiencing malevolent voices is associated with attentional dysfunction in psychotic patients. Scand J Psychol 2013;54:72-7.
5. Hugdahl K. Auditory hallucinations: A review of the ERC “VOICE” project. World J Psychiatr 2015;5:193-209
6. Kråkvik B, Larøi F, Kalhovde AM, Hugdahl K, Kompus K, Salvesen Ø, et al. Prevalence of auditory verbal hallucinations in a general population: A group comparison study. Scand J Psychol 2015;56:508-15.
7. Kompus K, Falkenberg L, Bless J, Johnsen E, Kroken RA, Kråkvik B, et al. The role of primary auditory cortex in the neural mechanism of auditory verbal hallucinations. Front Hum Neurosci 2013;7:144.
8. Larøi F, Sommer IE, Blom JD, Fernyhough C, Ffytche DH, Hugdahl K, et al. The characteristic features of auditory verbal hallucinations in clinical and non-clinical groups: State-of-the-art overview and future directions. Schizophr Bull 2012;38:724-33.
9. Waters F, Blom JD, Jardri R, Hugdahl K, Sommer IEC. Auditory hallucinations, not necessarily a hallmark of psychotic disorder. Psychol Med 2017:1-8.
10. Jones SR. Do we need multiple models of auditory verbal hallucinations? Examining the phenomenological fit of cognitive and neurological models. Schizophr Bull 2010;36:566-75.
11. Kompus K, Westerhausen R, Hugdahl K. The “paradoxical” engagement of the primary auditory cortex in patients with auditory verbal hallucinations: a metaanalysis of functional neuroimaging studies. Neuropsychologia 2011;49:3361-9.
12. van den Noort M, Specht K, Rimol LM, Ersland L, Hugdahl K. A new verbal reports fMRI dichotic listening paradigm for studies of hemispheric asymmetry. Neuroimage 2008;40:902-11.
13. Jardri R, Pouchet A, Pins D, Thomas P. Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. Am J Psychiatr 2011;168:73-81.
14. Sommer IE, Diederen KM, Blom JD, Willems A, Kushan L, Slotema K. et al. Auditory verbal hallucinations predominantly activate the right inferior frontal area. Brain 2008;131:3169-77.
15. Kühn S, Gallinat J. Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia. Schizophr Bull 2010;38:779-86.
16. Alonso-Solís A, Vives-Gilabert Y, Grasa E, Portella MJ, Rabella M, Sauras RB, et al. Resting-state functional connectivity alterations in the default network of schizophrenia patients with persistent auditory verbal hallucinations. Schizophr Res 2015;161:261-8.
17. Dierks T, Linden DEJ, Jandl M, Formisano E, Goebel R, Lanfermann H, et al. Activation of Heschl's gyrus during auditory hallucinations. Neuron 1999;22:615-21.
18. Ford JM, Dierks T, Fisher DJ, Herrmann CS, Hubl D, Kindler J, et al. Neurophysiological studies of auditory verbal hallucinations. Schizophr Bull 2012;38:715-23.
19. Jardri R, Hugdahl K, Hughes M, Brunelin J, Waters F, Alderson-Day B, et al. Are hallucinations due to an imbalance between excitatory and inhibitory influences on the brain? Schizophr Bull 2016;42:1124-34.
20. Chang X, Collin G, Xi Y, Cui L, Scholtens LH, Sommer IE, et al. Restingstate functional connectivity in medication-naïve schizophrenia patients with and without auditory verbal hallucinations: A preliminary report. Schizophr Bull 2017;188:75-81.
21. Ćurčić-Blake B, Ford JM, Hubl D, Orlov ND, Sommer IE, Waters F, et al. Interaction of language, auditory and memory brain networks in auditory verbal hallucinations. Progr Neurobiol 2017;148:1-20.
22. Bohlken MM, Hugdahl K, Sommer IE. Auditory verbal hallucinations: neuroimaging and treatment, Psychol Med 2017;47:199-208.
23. Woodruff PW, Wright IC, Bullmore ET, Brammer M, Howard RJ, Williams SC, et al. Auditory hallucinations and the temporal cortical response to speech in schizophrenia: A functional magnetic resonance imaging study. Am J Psychiatr 1997;154:1676-82.
24. Hubl D, Koening T, Strik WK, Garcia LM, Dierks T. Competition for neuronal resources: how hallucinations make themselves heard. Br J Psychiatr 2008;190:57-62.
25. Moseley P, Fernyhough C, Ellison A. The role of the superior temporal lobe in auditory false perceptions: a transcranial direct current stimulation study. Neuropsychologia 2014;62:202-8.
26. Falkenberg LE, Westerhausen R, Hugdahl K. Arcuate fasciculus size is associated with auditory hallucinations. Poster presented at SIRS Conference Firenze Italy; 2016.
27. Catani M, Craig MC, Forkel SJ, Kanaan R, Picchion M, Toulopoulou T, et al. Altered integrity of perisylvian language pathways in schizophrenia: Relationship to auditory hallucinations. Biol Psychiatr 2011;70:1143-50.
28. Hugdahl K, Løberg EM, Falkenberg LE, Johnsen E, Kompus K, Kroken R, et al. Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: Evidence from dichotic listening. Schizophr Res 2012;140:59-64.
29. Hugdahl K. Dichotic listening studies of brain asymmetry. Encycl Neurosci 2009;3:517-22.
30. Hugdahl K. Fifty years of dichotic listening research - Still going and going and. Brain Cogn 2011;76:211-3.
31. Hugdahl K, Andersson L. The "forced-attention paradigm" in dichotic listening to CV-syllables: A comparison between adults and children. Cortex 1986;22:417-32.
32. Hugdahl K, Westerhausen R, Alho K, Medvedev S, Laine M, Hämäläinen H. Attention and cognitive control: Unfolding the dichotic listening story. Scand J Psychol 2009;50:11-22.
33. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261-76.
34. Luhrmann TM, Padmavati R, Tharoor H, Osei A. Differences in voicehearing experiences of people with Psychosis in the U.S.A, India and Ghana: interview-based study. Br J Psychiatry 2015;206:41-4.
35. Javitt DC, Shelley AM, Silipo G, Lieberman JA Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern Arch Gen Psychiatr 2000;57:1131-7.
36. Zhang ZJ, Hao GF, Shi JB, Mou XD, Yao ZJ, Chen N. Investigation of the neural substrates of voice recognition in Chinese schizophrenic patients with auditory verbal hallucinations: an event-related functional MRI study. Acta Psychiatr Scand 2008;118:272-80.
37. Waters FA, Badcock JC. Memory for speech and voice identity in schizophrenia. J Nerv Ment Dis 2009;197:887-91.
38. Chhabra S, Badcock JC, Maybery MT, Leung D. Voice identity discrimination and hallucination-proneness in healthy young adults: a further challenge to the continuum model of psychosis? Cogn Neuropsychiatr 2014;19:305-18.
39. Alba-Ferrara L, Weis S, Damjanovic L, Rowett M, Hausmann M. Voice identity recognition failure in patients with schizophrenia. J Nerv Ment Dis 2012;200:784-90.
40. McLachlan NM, Phillips DS, Rossell SL, Wilson SJ. Auditory processing and hallucinations in schizophrenia. Schizophr Res 2013;150:380-5.
41. Hugdahl K, Craven AR, Nygård M, Løberg EM, Berle JØ, Johnsen E, et al. Glutamate as a mediating transmitter for auditory hallucinations in schizophrenia: a (1)H MRS study. Schizophr Res 2015;161: 252-60.
42. Ćurčić-Blake B, Bais L, Sibeijn-Kuiper A, Pijneborg HM, Knegtering H, Liemburg E, et al. Glutamate in dorsolateral prefrontal cortex and auditory verbal hallucinations in patients with schizophrenia: A 1H-MRS study. Prog Neuropsychopharmacol Biol Psychiatry 2017;78:132-9.
43. Chadwick P, Birchwood M. The omnipotence of voices II: The Beliefs About Voices Questionnaire (BAVQ). Br J Psychiatr 1995;166:773-6.
44. Chadwick P, Birchwood M. The omnipotence of voices. A cognitive approach to auditory hallucinations. Br J Psychiatr 1994;164:190-201.
45. Hugdahl K. "Hearing voices": auditory hallucinations as failure of top-down control of bottom-up perceptual processes. Scand J Psychol 2009;50:553-60.
46. LeDoux JE, Sakaguchi A, Iwata J, Reis DJ. Auditory emotional memories: establishment by projections from the medial geniculate nucleus to the posterior neostriatum and/or dorsal amygdala. Ann N Y Acad Sci 1985;444:463-4.
47. Bless JJ, Larøi F, Kompus K, Kråkvik, B, Vedul-Kjelsås E, Kalhovde AM, et al. (submitted). Does the occurrence of a triggering event at first onset influence characteristics of auditory hallucinations?