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Cerebral blood flow alterations specific to auditory verbal hallucinations in schizophrenia

  • Chuanjun Zhuo (a1), Jiajia Zhu (a2), Wen Qin (a2), Hongru Qu (a3), Xiaolei Ma (a3) and Chunshui Yu (a4)...

Auditory verbal hallucinations (AVHs) have been associated with deficits in auditory and speech-related networks. However, the resting-state cerebral blood flow (CBF) alterations specific to AVHs in schizophrenia remain unknown.


To explore AVH-related CBF alterations in individuals with schizophrenia.


In total, 35 individuals with schizophrenia with AVHs, 41 individuals with schizophrenia without AVHs and 50 controls underwent arterial spin labelling magnetic resonance imaging. The CBF differences were voxel-wise compared across the three groups.


We found AVH-specific CBF increase in the right superior temporal gyrus and caudate, and AVH-specific CBF decrease in the bilateral occipital and left parietal cortices. We also observed consistent CBF changes in both schizophrenia subgroups (i.e. those with and without AVHs) including decreased CBF in the bilateral occipital regions, the left lateral prefrontal and insular cortices, and the right anterior cingulate cortex and increased CBF in the bilateral lateral temporal regions and putamen, the left middle cingulate cortex and the right thalamus.


The AVH-specific CBF increases in the auditory and striatal areas and CBF reductions in the visual and parietal areas suggest that there exists a CBF redistribution associated with AVHs.

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Corresponding author
Chunshui Yu, MD, Department of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China. Email:
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These authors contributed equally to this work.

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1 Andreasen, NC, Flaum, M. Schizophrenia: the characteristic symptoms. Schizophr Bull 1991; 17: 2749.
2 David, AS. The cognitive neuropsychiatry of auditory verbal hallucinations: an overview. Cogn Neuropsychiatry 2004; 9: 107–23.
3 Hugdahl, K. Auditory hallucinations: a review of the ERC “VOICE” project. World J Psychiatry 2015; 5: 193209.
4 Gaite, L, Vazquez-Barquero, JL, Borra, C, Ballesteros, J, Schene, A, Welcher, B, et al. Quality of life in patients with schizophrenia in five European countries: the EPSILON study. Acta Psychiatr Scand 2002; 105: 283–92.
5 Shergill, SS, Murray, RM, McGuire, PK. Auditory hallucinations: a review of psychological treatments. Schizophr Res 1998; 32: 137–50.
6 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.
7 Allen, P, Laroi, F, McGuire, PK, Aleman, A. The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neurosci Biobehav Rev 2008; 32: 175–91.
8 Allen, P, Modinos, G, Hubl, D, Shields, G, Cachia, A, Jardri, R, et al. Neuroimaging auditory hallucinations in schizophrenia: from neuroanatomy to neurochemistry and beyond. Schizophr Bull 2012; 38: 695703.
9 Modinos, G, Costafreda, SG, van Tol, MJ, McGuire, PK, Aleman, A, Allen, P. Neuroanatomy of auditory verbal hallucinations in schizophrenia: a quantitative meta-analysis of voxel-based morphometry studies. Cortex 2013; 49: 1046–55.
10 Palaniyappan, L, Balain, V, Radua, J, Liddle, PF. Structural correlates of auditory hallucinations in schizophrenia: a meta-analysis. Schizophr Res 2012; 137: 169–73.
11 Geoffroy, PA, Houenou, J, Duhamel, A, Amad, A, De Weijer, AD, Curcic-Blake, B, et al. The arcuate fasciculus in auditory-verbal hallucinations: a meta-analysis of diffusion-tensor-imaging studies. Schizophr Res 2014; 159: 234–7.
12 Wigand, M, Kubicki, M, Clemm von Hohenberg, C, Leicht, G, Karch, S, Eckbo, R, et al. Auditory verbal hallucinations and the interhemispheric auditory pathway in chronic schizophrenia. World J Biol Psychiatry 2015; 16: 3144.
13 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: 7381.
14 Kuhn, S, Gallinat, J. Quantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia. Schizophr Bull 2012; 38: 779–86.
15 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.
16 Hoffman, RE, Hampson, M. Functional connectivity studies of patients with auditory verbal hallucinations. Front Hum Neurosci 2011; 6: 6.
17 Theberge, J. Perfusion magnetic resonance imaging in psychiatry. Top Magn Reson Imag 2008; 19: 111–30.
18 Kindler, J, Jann, K, Homan, P, Hauf, M, Walther, S, Strik, W, et al. Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia. Schizophr Bull 2015; 41: 163–70.
19 Liu, J, Qiu, M, Constable, RT, Wexler, BE. Does baseline cerebral blood flow affect task-related blood oxygenation level dependent response in schizophrenia? Schizophr Res 2012; 140: 143–8.
20 Pinkham, A, Loughead, J, Ruparel, K, Wu, WC, Overton, E, Gur, R, et al. Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI. Psychiatry Res 2011; 194: 6472.
21 Scheef, L, Manka, C, Daamen, M, Kuhn, KU, Maier, W, Schild, HH, et al. Resting-state perfusion in nonmedicated schizophrenic patients: a continuous arterial spin-labeling 3.0-T MR study. Radiology 2010; 256: 253–60.
22 Walther, S, Federspiel, A, Horn, H, Razavi, N, Wiest, R, Dierks, T, et al. Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia. Psychiatry Res 2011; 192: 117–24.
23 Zhu, J, Zhuo, C, Qin, W, Xu, Y, Xu, L, Liu, X, et al. Altered resting-state cerebral blood flow and its connectivity in schizophrenia. J Psychiatr Res 2015; 63: 2835.
24 Wolf, ND, Gron, G, Sambataro, F, Vasic, N, Frasch, K, Schmid, M, et al. Magnetic resonance perfusion imaging of auditory verbal hallucinations in patients with schizophrenia. Schizophr Res 2012; 134: 285–7.
25 First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM-IV Axis I Disorders – Clinician Version (SCID-CV). American Psychiatric Press, 1997.
26 Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76.
27 Hoffman, RE, Hawkins, KA, Gueorguieva, R, Boutros, NN, Rachid, F, Carroll, K, et al. Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations. Arch Gen Psychiatry 2003; 60: 4956.
28 Andreasen, NC. Methods for assessing positive and negative symptoms. Mod Probl Pharmacopsychiatry 1990; 24: 7388.
29 Gardner, DM, Murphy, AL, O'Donnell, H, Centorrino, F, Baldessarini, RJ. International consensus study of antipsychotic dosing. Am J Psychiatry 2010; 167: 686–93.
30 Moran, LV, Sampath, H, Kochunov, P, Hong, LE. Brain circuits that link schizophrenia to high risk of cigarette smoking. Schizophr Bull 2013; 39: 1373–81.
31 Buxton, RB, Frank, LR, Wong, EC, Siewert, B, Warach, S, Edelman, RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 1998; 40: 383–96.
32 Xu, G, Rowley, HA, Wu, G, Alsop, DC, Shankaranarayanan, A, Dowling, M, et al. Reliability and precision of pseudo-continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O-water PET in elderly subjects at risk for Alzheimer's disease. NMR Biomed 2010; 23: 286–93.
33 Friston, KJ, Ashburner, J, Kiebel, SJ, Nichols, TE, Penny, WD. Statistical Parametric Mapping: The Analysis of Functional Brain Images. Academic Press, 2007.
34 Aslan, S, Lu, H. On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow. Magn Reson Imaging 2010; 28: 928–35.
35 Vercammen, A, Knegtering, H, Bruggeman, R, Westenbroek, HM, Jenner, JA, Slooff, CJ, et al. Effects of bilateral repetitive transcranial magnetic stimulation on treatment resistant auditory-verbal hallucinations in schizophrenia: a randomized controlled trial. Schizophr Res 2009; 114: 172–9.
36 Gur, RC, Gur, RE. Hypofrontality in schizophrenia: RIP. Lancet 1995; 345: 1383–4.
37 Manoliu, A, Riedl, V, Zherdin, A, Muhlau, M, Schwerthoffer, D, Scherr, M, et al. Aberrant dependence of default mode/central executive network interactions on anterior insular salience network activity in schizophrenia. Schizophr Bull 2014; 40: 428–37.
38 Butler, PD, Schechter, I, Zemon, V, Schwartz, SG, Greenstein, VC, Gordon, J, et al. Dysfunction of early-stage visual processing in schizophrenia. Am J Psychiatry 2001; 158: 1126–33.
39 Byne, W, Hazlett, EA, Buchsbaum, MS, Kemether, E. The thalamus and schizophrenia: current status of research. Acta Neuropathologica 2009; 117: 347–68.
40 Onitsuka, T, Shenton, ME, Salisbury, DF, Dickey, CC, Kasai, K, Toner, SK, et al. Middle and inferior temporal gyrus gray matter volume abnormalities in chronic schizophrenia: an MRI study. Am J Psychiatry 2004; 161: 1603–11.
41 Perez-Costas, E, Melendez-Ferro, M, Roberts, RC. Basal ganglia pathology in schizophrenia: dopamine connections and anomalies. J Neurochemistry 2010; 113: 287302.
42 Sommer, IE, de Weijer, AD, Daalman, K, Neggers, SF, Somers, M, Kahn, RS, et al. Can fMRI-guidance improve the efficacy of rTMS treatment for auditory verbal hallucinations? Schizophr Res 2007; 93: 406–8.
43 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.
44 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 Psychiatry 1997; 154: 1676–82.
45 van Swam, C, Federspiel, A, Hubl, D, Wiest, R, Boesch, C, Vermathen, P, et al. Possible dysregulation of cortical plasticity in auditory verbal hallucinations – a cortical thickness study in schizophrenia. J Psychiatr Res 2012; 46: 1015–23.
46 Downar, J, Crawley, AP, Mikulis, DJ, Davis, KD. A multimodal cortical network for the detection of changes in the sensory environment. Nature Neurosci 2000; 3: 277–83.
47 Knecht, S, Drager, B, Deppe, M, Bobe, L, Lohmann, H, Floel, A, et al. Handedness and hemispheric language dominance in healthy humans. Brain 2000; 123: 2512–8.
48 Strauss, E, Wada, J. Lateral preferences and cerebral speech dominance. Cortex 1983; 19: 165–77.
49 Van Lancker, D, Cummings, JL. Expletives: neurolinguistic and neurobehavioral perspectives on swearing. Brain Res Rev 1999; 31: 83104.
50 Copolov, D, Trauer, T, Mackinnon, A. On the non-significance of internal versus external auditory hallucinations. Schizophr Res 2004; 69: 16.
51 Stephane, M, Thuras, P, Nasrallah, H, Georgopoulos, AP. The internal structure of the phenomenology of auditory verbal hallucinations. Schizophr Res 2003; 61: 185–93.
52 Hugdahl, K, Carlsson, G, Uvebrant, P, Lundervold, AJ. Dichotic-listening performance and intracarotid injections of amobarbital in children and adolescents. Preoperative and postoperative comparisons. Arch Neurol 1997; 54: 1494–500.
53 Zaidel, DW. Memory for scenes in stroke patients. Hemisphere processing of semantic organization in pictures. Brain 1986; 109: 547–60.
54 Horga, G, Parellada, E, Lomena, F, Fernandez-Egea, E, Mane, A, Font, M, et al. Differential brain glucose metabolic patterns in antipsychotic-naive first-episode schizophrenia with and without auditory verbal hallucinations. J Psychiatry Neurosci 2011; 36: 312–21.
55 O'Daly, OG, Frangou, S, Chitnis, X, Shergill, SS. Brain structural changes in schizophrenia patients with persistent hallucinations. Psychiatry Res 2007; 156: 1521.
56 Gil Robles, S, Gatignol, P, Capelle, L, Mitchell, MC, Duffau, H. The role of dominant striatum in language: a study using intraoperative electrical stimulations. J Neurol Neurosurg Psychiatry 2005; 76: 940–6.
57 Abutalebi, J, Annoni, JM, Zimine, I, Pegna, AJ, Seghier, ML, Lee-Jahnke, H, et al. Language control and lexical competition in bilinguals: an event-related fMRI study. Cereb Cortex 2008; 18: 1496–505.
58 Crinion, J, Turner, R, Grogan, A, Hanakawa, T, Noppeney, U, Devlin, JT, et al. Language control in the bilingual brain. Science 2006; 312: 1537–40.
59 Humphreys, GF, Lambon Ralph, MA. Fusion and fission of cognitive functions in the human parietal cortex. Cereb Cortex 2015; 25: 3547–60.
60 Mars, RB, Jbabdi, S, Sallet, J, O'Reilly, JX, Croxson, PL, Olivier, E, et al. Diffusion-weighted imaging tractography-based parcellation of the human parietal cortex and comparison with human and macaque resting-state functional connectivity. J Neurosci 2011; 31: 4087–100.
61 Nelson, SM, Cohen, AL, Power, JD, Wig, GS, Miezin, FM, Wheeler, ME, et al. A parcellation scheme for human left lateral parietal cortex. Neuron 2010; 67: 156–70.
62 Shomstein, S. Cognitive functions of the posterior parietal cortex: top-down and bottom-up attentional control. Front Integr Neurosci 2012; 6: 38.
63 Koenigs, M, Barbey, AK, Postle, BR, Grafman, J. Superior parietal cortex is critical for the manipulation of information in working memory. J Neurosci 2009; 29: 14980–6.
64 Walther, S, Strik, W. Motor symptoms and schizophrenia. Neuropsychobiology 2012; 66: 7792.
65 Lee, J, Park, S. Working memory impairments in schizophrenia: a meta-analysis. J Abnorm Psychol 2005; 114: 599611.
66 Neuhaus, AH, Karl, C, Hahn, E, Trempler, NR, Opgen-Rhein, C, Urbanek, C, et al. Dissection of early bottom-up and top-down deficits during visual attention in schizophrenia. Clin Neurophysiol 2011; 122: 90–8.
67 Covington, MA, He, C, Brown, C, Naci, L, McClain, JT, Fjordbak, BS, et al. Schizophrenia and the structure of language: the linguist's view. Schizophr Res 2005; 77: 8598.
68 Loberg, EM, Jorgensen, HA, Kroken, RA, Johnsen, E. Auditory verbal hallucinations reflect stable auditory attention deficits: a prospective study. Cogn Neuropsychiatry 2015; 20: 8194.
69 Papageorgiou, C, Oulis, P, Vasios, C, Kontopantelis, E, Uzunoglu, N, Rabavilas, A, et al. P300 alterations in schizophrenic patients experiencing auditory hallucinations. Eur Neuropsychopharmacol 2004; 14: 227–36.
70 Hoffman, RE, Rapaport, J, Mazure, CM, Quinlan, DM. Selective speech perception alterations in schizophrenic patients reporting hallucinated “voices”. Am J Psychiatry 1999; 156: 393–9.
71 Gisselgard, J, Anda, LG, Bronnick, K, Langeveld, J, Ten Velden Hegelstad, W, Joa, I, et al. Verbal working memory deficits predict levels of auditory hallucination in first-episode psychosis. Schizophr Res 2014; 153: 3841.
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Cerebral blood flow alterations specific to auditory verbal hallucinations in schizophrenia

  • Chuanjun Zhuo (a1), Jiajia Zhu (a2), Wen Qin (a2), Hongru Qu (a3), Xiaolei Ma (a3) and Chunshui Yu (a4)...
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