Functional connectivity of the temporo-parietal region in schizophrenia: Effects of rTMS treatment of auditory hallucinations Ans Vercammen a,b, * , Henderikus Knegtering c,d , Edith J. Liemburg a,b , Johannes A. den Boer c , André Aleman a,b a Department of Neuroscience, University Medical Center Groningen, The Netherlands b BCN NeuroImaging Center, University of Groningen, The Netherlands c Department of Psychiatry, University Medical Center Groningen, The Netherlands d Lentis Mental Health Care Center, Groningen, The Netherlands article info Article history: Received 14 September 2009 Received in revised form 26 November 2009 Accepted 22 December 2009 Keywords: Auditory-verbal hallucinations Schizophrenia fMRI Resting state activity rTMS abstract Auditory-verbal hallucinations are a hallmark symptom of schizophrenia. In recent years, repetitive transcranial magnetic stimulation (rTMS) targeting speech perception areas has been advanced as a potential treatment of medication-resistant hallucinations. However, the underlying neural processes remain unclear. This study aimed to assess whether 1 Hz rTMS treatment would affect functional connectivity of the temporo-parietal junction (TPJ). Resting state fMRI scans were obtained from 18 patients with schizo- phrenia. Patients were assessed before and after a 6 day treatment with 1 Hz rTMS to the left TPJ, or pla- cebo treatment with sham rTMS to the same location. We assessed functional connectivity between a priori defined regions-of-interest (ROIs) comprising the putative AVH network and the bilateral TPJ seed regions, targeted with rTMS. Symptom improvement following rTMS treatment was observed in the left rTMS group, whereas no change at occurred in the placebo group. Although no corresponding changes were observed in the func- tional connections previously found to be associated with AVH severity, an increase in connectivity between the left TPJ and the right insula was observed in group receiving rTMS to the left TPJ. The placebo group conversely showed a decrease in connectivity between the left TPJ and left anterior cingulate. We conclude that application of 1 Hz rTMS to the left TPJ region may affect functional connectivity of the targeted region. However, the relationship between these functional changes during the resting state and the rate of clinical improvement needs further clarification. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Auditory-verbal hallucinations (AVH) are a hallmark symptom of schizophrenia (Andreasen and Flaum, 1991). Despite decades of research, the cognitive and neural basis of hallucinations remain unclear (Aleman and Laroi, 2008). Neuroimaging studies have made significant strides however, to unearth structural and func- tional abnormalities associated with AVH in a distributed network of brain regions involved in linguistic processing, attention, mem- ory and emotion, including Broca’s area, insula, the amygdala-hip- pocampal complex and a number of subcortical regions (Allen et al., 2008). Most consistently reported are the speech processing regions of the posterior superior temporal cortex of the language dominant left hemisphere, both in terms of anatomical (Barta et al., 1990; Flaum et al., 1995; Rajarethinam et al., 2000; Levitan et al., 1999; Onitsuka et al., 2004) and functional alterations (Suzu- ki et al., 1993; Dierks et al., 1999; van de Ven et al., 2005). Some studies have reported involvement of right hemispheric language areas as well (Lennox et al., 2000; Shergill et al., 2000; Sommer et al., 2008). In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as an encouraging new treatment for auditory hallucinations. Under the assumption that rTMS may have benefi- cial inhibitory effects on the pathologically overactivated speech processing cortex in voice hearers, Hoffman et al. (1999) published the first report demonstrating a reduction in AVH after 1 Hz rTMS to the posterior superior temporal gyrus (STG). A number of stud- ies have now replicated these preliminary findings (Poulet et al., 2005; Brunelin et al., 2006; Chibbaro et al., 2005; d’Alfonso et al., 2002; Lee et al., 2005; Hoffman et al., 2003, 2005; Sommer et al., 2007; McIntosh et al., 2004; Schonfeldt-Lecuona et al., 2004), and 0022-3956/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jpsychires.2009.12.011 * Corresponding author. Address: BCN NeuroImaging Center, Antonius Deus- inglaan 2, 9713 AW Groningen, The Netherlands. Tel.: +31 (0)50 363 8999; fax: +31 (0)50 363 8875. E-mail address: a.vercammen@med.umcg.nl (A. Vercammen). Journal of Psychiatric Research 44 (2010) 725–731 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires