Skip to main content

Aberrant resting-state connectivity in non-psychotic individuals with auditory hallucinations

  • K. M. J. Diederen (a1), S. F. W. Neggers (a1), A. D. de Weijer (a1), R. van Lutterveld (a1), K. Daalman (a1), S. B. Eickhoff (a2) (a3) (a4), M. Clos (a2), R. S. Kahn (a1) and I. E. C. Sommer (a1)...

Although auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH.


Resting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR.


In comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group.


Aberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.

Corresponding author
*Address for correspondence: K. M. J. Diederen, Ph.D., Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Place, Cambridge CB2 3DY, UK. (Email:
Hide All
Aleman A, Laroi F (2008). Hallucinations: The Science of Idiosyncratic Perception. American Psychological Association: Washington, DC.
Allen P, Amaro E, Fu CH, Williams SC, Brammer MJ, Johns LC, McGuire PK (2007). Neural correlates of the misattribution of speech in schizophrenia. British Journal of Psychiatry 190, 162169.
Allen P, Laroi F, McGuire PK, Aleman A (2008). The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neuroscience and Biobehavioral Reviews 32, 175191.
Andreasen NC, Flaum M, Arndt S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615623.
Ashburner J, Friston KJ (2005). Unified segmentation. NeuroImage 26, 839851.
Birn RM, Diamond JB, Smith MA, Bandettini PA (2006). Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. NeuroImage 31, 15361548.
Chang C, Glover GH (2009). Effects of model-based physiological noise correction on default mode network anti-correlations and correlations. NeuroImage 47, 14481459.
Cole DM, Smith SM, Beckmann CF (2010). Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Frontiers in Systems Neuroscience 4, 8.
Copolov DL, Seal ML, Maruff P, Ulusoy R, Wong MT, Tochon-Danguy HJ, Egan GF (2003). Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study. Psychiatry Research 122, 139152.
Daalman K, Boks MP, Diederen KM, de Weijer AD, Blom JD, Kahn RS, Sommer IE (2011). The same or different? A phenomenological comparison of auditory verbal hallucinations in healthy and psychotic individuals. Journal of Clinical Psychiatry 72, 320325.
Dagli MS, Ingeholm JE, Haxby JV (1999). Localization of cardiac-induced signal change in fMRI. NeuroImage 9, 407415.
de Weijer AD, Mandl RC, Diederen KM, Neggers SF, Kahn RS, Hulshoff Pol HE, Sommer IE (2011 a). Microstructural alterations of the arcuate fasciculus in schizophrenia patients with frequent auditory verbal hallucinations. Schizophrenia Research 130, 6877.
de Weijer AD, Neggers SF, Diederen KM, Mandl RC, Kahn RS, Hulshoff Pol HE, Sommer IE (2011 b). Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals. Human Brain Mapping. Published online: 23 November 2011. doi:10.1002/hbm.21463.
Diederen KM, Daalman K, de Weijer AD, Neggers SF, van Gastel W, Blom JD, Kahn RS, Sommer IE (2011). Auditory hallucinations elicit similar brain activation in psychotic and nonpsychotic individuals. Schizophrenia Bulletin 38, 10741082.
Diederen KM, De Weijer AD, Daalman K, Blom JD, Neggers SF, Kahn RS, Sommer IE (2010 a). Decreased language lateralization is characteristic of psychosis, not auditory hallucinations. Brain 133, 37343744.
Diederen KM, Neggers SF, Daalman K, Blom JD, Goekoop R, Kahn RS, Sommer IE (2010 b). Deactivation of the parahippocampal gyrus preceding auditory hallucinations in schizophrenia. American Journal of Psychiatry 167, 427435.
Diederen KM, van Lutterveld R, Sommer IE (2012). Neuroimaging of voice hearing in non-psychotic individuals: a mini review. Frontiers in Human Neuroscience 6, 111.
Eichenbaum H (2000). A cortical-hippocampal system for declarative memory. Nature Reviews. Neuroscience 1, 4150.
Eichenbaum H, Schoenbaum G, Young B, Bunsey M (1996). Functional organization of the hippocampal memory system. Proceedings of the National Academy of Sciences USA 93, 1350013507.
Eichenbaum H, Yonelinas AP, Ranganath C (2007). The medial temporal lobe and recognition memory. Annual Reviews of Neuroscience 30, 123152.
Endicott J, Spitzer RL, Fleiss JL, Cohen J (1976). The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766771.
Ford JM, Roach BJ, Faustman WO, Mathalon DH (2007). Synch before you speak: auditory hallucinations in schizophrenia. American Journal of Psychiatry 164, 458466.
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences USA 102, 96739678.
Frith CD, Friston KJ, Herold S, Silbersweig D, Fletcher P, Cahill C, Dolan RJ, Frackowiak RS, Liddle PF (1995). Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task. British Journal of Psychiatry 167, 343349.
Gavrilescu M, Rossell S, Stuart GW, Shea TL, Innes-Brown H, Henshall K, McKay C, Sergejew AA, Copolov D, Egan GF (2010). Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study. Psychological Medicine 40, 11491158.
Glover GH, Lee AT (1995). Motion artifacts in fMRI: comparison of 2DFT with PR and spiral scan methods. Magnetic Resonance in Medicine 33, 624635.
Glover GH, Li TQ, Ress D (2000). Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magnetic Resonance in Medicine 44, 162167.
Greicius MD, Krasnow B, Reiss AL, Menon V (2003). Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences USA 100, 253258.
Heinks-Maldonado TH, Mathalon DH, Houde JF, Gray M, Faustman WO, Ford JM (2007). Relationship of imprecise corollary discharge in schizophrenia to auditory hallucinations. Archives in General Psychiatry 64, 286296.
Hoffman RE, Anderson AW, Varanko M, Gore JC, Hampson M. (2008). Time course of regional brain activation associated with onset of auditory/verbal hallucinations. British Journal of Psychiatry 193, 424425.
Hoffman RE, Fernandez T, Pittman B, Hampson M (2010). Elevated functional connectivity along a corticostriatal loop and the mechanism of auditory/verbal hallucinations in patients with schizophrenia. Biological Psychiatry 69, 407414.
Hoffman RE, Pittman B, Constable RT, Bhagwagar Z, Hampson M (2011). Time course of regional brain activity accompanying auditory verbal hallucinations in schizophrenia. British Journal of Psychiatry 198, 277283.
Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, Sharma T (1999). Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proceedings of the National Academy of Sciences USA 96, 1343213437.
Jardri R, Pouchet A, Pins D, Thomas P (2010). Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. American Journal of Psychiatry 168, 7381.
Johnson JD, Rugg MD (2007). Recollection and the reinstatement of encoding-related cortical activity. Cerebral Cortex 17, 25072515.
Kuhn S, Gallinat J (2010). Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia. Schizophrenia Bulletin 38, 779786.
Liemburg EJ, Vercammen A, Ter Horst GJ, Curcic-Blake B, Knegtering H, Aleman A (2012). Abnormal connectivity between attentional, language and auditory networks in schizophrenia. Schizophrenia Research 135, 1522.
Lund TE, Madsen KH, Sidaros K, Luo W-L, Nichols TE (2006). Non-white noise in fMRI: does modelling have an impact? NeuroImage 29, 5466.
McGuire PK, Frith CD (1996). Disordered functional connectivity in schizophrenia. Psychological Medicine 26, 663667.
Murphy K, Birn RM, Handwerker DA, Jones TB, Bandettini PA (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? NeuroImage 44, 893905.
Neggers SF, Hermans EJ, Ramsey NF (2008). Enhanced sensitivity with fast three-dimensional blood-oxygen-level-dependent functional MRI: comparison of SENSE-PRESTO and 2D-EPI at 3 T. Nuclear Magnetic Resonance in Biomedicine 21, 663676.
Noll DC, Schneider W (1994). Theory, simulation, and compensation of physiological motion artifacts in functional MRI. Image Processing, 1994. Proceedings. ICIP-94, IEEE International Conference 3, 4044.
Ojemann GA (1991). Cortical organization of language. Journal of Neuroscience 11, 22812287.
Raine A (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17, 555564.
Rotarska-Jagiela A, van de Ven V, Oertel-Knochel V, Uhlhaas PJ, Vogeley K, Linden DE (2010). Resting-state functional network correlates of psychotic symptoms in schizophrenia. Schizophrenia Research 117, 2130.
Shergill SS, Kanaan RA, Chitnis XA, O'Daly O, Jones DK, Frangou S, Williams SC, Howard RJ, Barker GJ, Murray RM, McGuire P (2007). A diffusion tensor imaging study of fasciculi in schizophrenia. American Journal of Psychiatry 164, 467473.
Shergill SS, Murray RM, McGuire PK (1998). Auditory hallucinations: a review of psychological treatments. Schizophrenia Research 32, 137150.
Silbersweig DA, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua SE, Schnorr L, Jones T, Frackowiak RSJ (1995). A functional neuroanatomy of hallucinations in schizophrenia. Nature 378, 176179.
Sommer IE, Clos M, Meijering AL, Diederen KMJ, Eickhoff SB (2012). Resting state functional connectivity in patients with chronic hallucinations. PLoS ONE 7, e43516.
Sommer IE, Daalman K, Rietkerk T, Diederen KM, Bakker S, Wijkstra J, Boks MP (2008 a). Healthy individuals with auditory verbal hallucinations; who are they? Psychiatric assessments of a selected sample of 103 subjects. Schizophrenia Bulletin 36, 633641.
Sommer IE, Diederen KM, Blom JD, Willems A, Kushan L, Slotema K, Boks MP, Daalman K, Hoek HW, Neggers SF, Kahn RS (2008 b). Auditory verbal hallucinations predominantly activate the right inferior frontal area. Brain 131, 31693177.
Spence SA, Liddle PF, Stefan MD, Hellewell JS, Sharma T, Friston KJ, Hirsch SR, Frith CD, Murray RM, Deakin JF, Grasby PM (2000). Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised. British Journal of Psychiatry 176, 5260.
Spitzer RL, Williams JB, Gibbon M, First MB (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624629.
Tien AY (1991). Distributions of hallucinations in the population. Social Psychiatry and Psychiatric Epidemiology 26, 287292.
van Buuren M, Gladwin TE, Zandbelt BB, van den Heuvel M, Ramsey NF, Kahn RS, Vink M (2009). Cardiorespiratory effects on default-mode network activity as measured with fMRI. Human Brain Mapping 30, 30313042.
Van Hoesen GW (1982). The parahippocampal gyrus: new observations regarding its cortical connections in the monkey. Trends in Neurosciences 5, 345350.
van Lutterveld R, Oranje B, Kemner C, Abramovic L, Willems AE, Boks MP, Glenthoj BY, Kahn RS, Sommer IE (2010). Increased psychophysiological parameters of attention in non-psychotic individuals with auditory verbal hallucinations. Schizophrenia Research 121, 153159.
van Marle HJF, Hermans EJ, Qin S, Fernández G (2010). Enhanced resting-state connectivity of amygdala in the immediate aftermath of acute psychological stress. NeuroImage 53, 348354.
Vercammen A, Knegtering H, den Boer JA, Liemburg EJ, Aleman A (2010). Auditory hallucinations in schizophrenia are associated with reduced functional connectivity of the temporo-parietal area. Biological Psychiatry 67, 912918.
Wheeler ME, Petersen SE, Buckner RL (2000). Memory's echo: vivid remembering reactivates sensory-specific cortex. Proceedings of the National Academy of Sciences USA 97, 1112511129.
Williams JB, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, Howes MJ, Kane J, Pope Jr. HG, Rounsaville B, Wittchen HU (1992). The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Archives of General Psychiatry 49, 630636.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 7
Total number of PDF views: 42 *
Loading metrics...

Abstract views

Total abstract views: 350 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st November 2017. This data will be updated every 24 hours.