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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:


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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.


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)...


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