Kelly M J Diederen

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (37)212.01 Total impact

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    ABSTRACT: Symptoms that are linked to psychosis are also experienced by individuals who are not in need of care. In the present study, cortical thickness was investigated in these individuals. Fifty individuals with non-clinical auditory verbal hallucinations (most of them also experienced other non-clinical psychotic symptoms), 50 patients with a psychotic disorder and auditory verbal hallucinations, and 50 healthy control subjects underwent structural magnetic resonance imaging. Data were analysed using FreeSurfer. Cortical thickness in the pars orbitalis, paracentral lobule, fusiform gyrus and inferior temporal gyrus was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in control subjects. The patients also showed thinning in widespread additional areas compared to the two other groups, whereas both hallucinating groups showed similar levels of thinning in the insula. Ranking the levels of cortical thickness per brain region across groups revealed that for 88% of brain regions, cortical thickness was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in controls. These findings show that individuals with non-clinical psychotic symptoms show a similar but less pronounced pattern of cortical thinning as patients with a psychotic disorder, which is suggestive of a similar, but milder underlying pathophysiology in this group compared to the psychosis group.
    Brain 06/2014; · 10.23 Impact Factor
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    ABSTRACT: Symptoms that are linked to psychosis are also experienced by individuals who are not in need of care. In the present study, cortical thickness was investigated in these individuals. Fifty individuals with non-clinical auditory verbal hallucinations (most of them also experienced other non-clinical psychotic symptoms), 50 patients with a psychotic disorder and auditory verbal hallucinations, and 50 healthy control subjects underwent structural magnetic resonance imaging. Data were analysed using FreeSurfer. Cortical thickness in the pars orbitalis, paracentral lobule, fusiform gyrus and inferior temporal gyrus was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in control subjects. The patients also showed thinning in widespread additional areas compared to the two other groups, whereas both hallucinating groups showed similar levels of thinning in the insula. Ranking the levels of cortical thickness per brain region across groups revealed that for 88% of brain regions, cortical thickness was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in controls. These findings show that individuals with non-clinical psychotic symptoms show a similar but less pronounced pattern of cortical thinning as patients with a psychotic disorder, which is suggestive of a similar, but milder underlying pathophysiology in this group compared to the psychosis group.
    Brain 06/2014; 137. DOI:10.1093/brain/awu167 · 10.23 Impact Factor
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    ABSTRACT: Background: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia and can severely disrupt behavior and decrease quality of life. Identification of areas with high functional connectivity (so-called hub regions) that are associated with the predisposition to hallucinate may provide potential targets for neuromodulation in the treatment of AVH. Methods: Resting-state fMRI scans during which no hallucinations had occurred were acquired from 29 nonpsychotic individuals with AVH and 29 matched controls. These nonpsychotic individuals with AVH provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. Hub regions were identified by assessing weighted connectivity strength and betweenness centrality across groups using a permutation analysis. Results: Nonpsychotic individuals with AVH exhibited increased functioning as hub regions in the temporal cortices and the posterior cingulate/precuneus, which is an important area in the default mode network (DMN), compared to the nonhallucinating controls. In addition, the right inferior temporal gyrus, left paracentral lobule and right amygdala were less important as a hub region in the AVH group. Conclusions: These results suggest that the predisposition to hallucinate may be related to aberrant functioning of the DMN and the auditory cortices. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2014; 35(4). DOI:10.1002/hbm.22264 · 6.92 Impact Factor
  • European Psychiatry 01/2014; 29:1. DOI:10.1016/S0924-9338(14)78339-7 · 3.21 Impact Factor
  • Kirstin Daalman, Kelly M. Diederen
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    ABSTRACT: Although auditory verbal hallucinations (AVH) are a cardinal symptom of schizophrenia, they are frequently described on a continuum, ranging from patients diagnosed with a psychotic disorder to non-clinical populations. A key difference between these groups, however, is the absence of additional symptomatology as well as medication use in the group of non-clinical individuals, thus providing an excellent opportunity to study voices in relative isolation. However, this relies on the rather challenging assumption that AVH in clinical and non-clinical individuals can be considered the same phenomenon resulting from a common neurobiological substrate. Studies comparing voices between these groups might provide support for or against this assumption. Furthermore, increasing knowledge about AVH in non-clinical individuals might help eliminate ideas that AVH are always related to a need for care and could hence help to put voices in a more positive light. The aim of this review was therefore to review and summarize studies on AVH in non-clinical individuals with a main focus on the comparison between non-clinical individuals with AVH and individuals diagnosed with a psychotic disorder. Both groups displayed similar brain activation during the experience of AVH, showed aberrant brain connectivity and an increased rate of childhood traumas.
    Psychosis 10/2013; 5(3):236-246. DOI:10.1080/17522439.2013.796402
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    Schizophrenia Research 07/2013; DOI:10.1016/j.schres.2013.07.021 · 4.43 Impact Factor
  • Klinische Neurophysiologie 03/2013; 44(01). DOI:10.1055/s-0033-1337208 · 0.33 Impact Factor
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    ABSTRACT: INTRODUCTION: Verbal auditory hallucinations (VAHs) are experienced as spoken voices which seem to originate in the extracorporeal environment or inside the head. Animal and human research has identified a 'where' pathway for sound processing comprising the planum temporale, the middle frontal gyrus and the inferior parietal lobule. We hypothesize that increased activity of that 'where' pathway mediates the exteriorization of VAHs. METHODS: The fMRI scans of 52 right-handed psychotic patients experiencing frequent VAHs were compared with the reported location of hallucinations, as rated with the aid of the PSYRATS-AHRS. For each subject, a unique VAH activation model was created based on the VAH timings, and subsequently convolved with a gamma function to model the hemodynamic response. In order to examine the neurofunctional equivalents of perceived VAH location, second-level group effects of subjects experiencing either internal (n=24) or external (n=28) VAHs were contrasted within planum temporale, middle frontal gyrus, and inferior parietal lobule regions of interest (ROIs). RESULTS: Three ROIs were tested for increased activity in relation with the exteriorization of VAHs. The analysis revealed a left-sided medial planum temporale and a right-sided middle frontal gyrus cluster of increased activity. No significant activity was found in the inferior parietal lobule. CONCLUSIONS: Our study indicates that internal and external VAHs are mediated by a fronto-temporal pattern of neuronal activity while the exteriorization of VAHs stems from additional brain activity in the auditory 'where' pathway, comprising the planum temporale and prefrontal regions.
    Schizophrenia Research 03/2013; 146(1-3). DOI:10.1016/j.schres.2013.02.004 · 4.43 Impact Factor
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    ABSTRACT: Previous studies investigated fMRI-guided repetitive Transcranial Magnetic Stimulation (rTMS) as an alternative treatment for auditory verbal hallucinations (AVH). This tailor-made treatment focuses at directing the rTMS coil to the location where hallucinatory activation is maximal, as identified with fMRI scans of individual patients. For the effective use of such treatment it is important to determine whether brain activation during AVH can be reliably detected using fMRI. Thirty-three psychotic patients indicated the presence of AVH during two subsequent scans. Reproducibility was measured by calculating 1) the distance between local maxima of significantly activated clusters and 2) percentage overlap of activation patterns over the two scans. These measurements were obtained both in single subjects and on group-level in five regions of interest (ROIs). ROIs consisted of the areas that were most frequently activated during AVH. Scans were considered reproducible if the distance between local maxima was smaller than 2cm, as rTMS-treatment may target an area of approximately 2-4cm. The median distance between local maxima was smaller than 2cm for all ROIs on single-subject level, as well as on group-level. In addition, on single-subject level median percentage overlap varied between 14 and 38% for the different ROIs. On group-level, this was substantially higher with percentages overlap varying between 34 and 98%. Based on these results, AVH-scans may be considered sufficiently reproducible to be suitable for fMRI-guided rTMS treatment.
    Schizophrenia Research 02/2013; 146(1-3). DOI:10.1016/j.schres.2013.01.025 · 4.43 Impact Factor
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    ABSTRACT: Auditory verbal hallucinations (AVH) are a hallmark of psychotic experience. Various mechanisms including misattribution of inner speech and imbalance between bottom-up and top-down factors in auditory perception potentially due to aberrant connectivity between frontal and temporo-parietal areas have been suggested to underlie AVH. Experimental evidence for disturbed connectivity of networks sustaining auditory-verbal processing is, however, sparse. We compared functional resting-state connectivity in 49 psychotic patients with frequent AVH and 49 matched controls. The analysis was seeded from the left middle temporal gyrus (MTG), thalamus, angular gyrus (AG) and inferior frontal gyrus (IFG) as these regions are implicated in extracting meaning from impoverished speech-like sounds. Aberrant connectivity was found for all seeds. Decreased connectivity was observed between the left MTG and its right homotope, between the left AG and the surrounding inferior parietal cortex (IPC) and the left inferior temporal gyrus, between the left thalamus and the right cerebellum, as well as between the left IFG and left IPC, and dorsolateral and ventrolateral prefrontal cortex (DLPFC/VLPFC). Increased connectivity was observed between the left IFG and the supplementary motor area (SMA) and the left insula and between the left thalamus and the left fusiform gyrus/hippocampus. The predisposition to experience AVH might result from decoupling between the speech production system (IFG, insula and SMA) and the self-monitoring system (DLPFC, VLPFC, IPC) leading to misattribution of inner speech. Furthermore, decreased connectivity between nodes involved in speech processing (AG, MTG) and other regions implicated in auditory processing might reflect aberrant top-down influences in AVH.
    Brain Structure and Function 02/2013; DOI:10.1007/s00429-013-0519-5 · 7.84 Impact Factor
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    ABSTRACT: INTRODUCTION: Neuroimaging studies investigating auditory verbal hallucinations (AVH) have revealed involvement of several cortical structures. These findings may however be biased by brain activity related to stimulus detection and motor processes associated with the task to indicate the presence of AVH. Disentangling brain activation specifically related to AVH and to additional cognitive processes may help focus on the true neuronal substrates of AVH and strengthen the development of new focal treatment strategies. METHODS: Brain activation during AVH as indicated by button press was compared to brain activation during auditory stimulus detection indicated by button press. We performed two neuroimaging meta-analyses, assessing 10 AVH and 11 auditory stimulus detection studies. A random-effects activation likelihood estimation was performed using GingerALE to assess commonalities and differences across AVH and stimulus detection studies. RESULTS: Activity in the claustrum, pulvinar area, medial geniculum body, pyramis, culmen, putamen, insula, and parahippocampal, medial frontal, precentral, postcentral, superior temporal and right inferior frontal gyri was found to be specifically related to AVH. The pars opercularis of the left inferior frontal gyrus and the left transverse temporal gyrus were activated to a similar extent during AVH and auditory stimulus detection. DISCUSSION: Development of new focal treatment strategies for AVH may focus on the areas uniquely activated in the AVH analysis. The pars opercularis and the transverse temporal gyrus may not be directly involved in the experience of AVH itself, but rather in auditory stimulus detection.
    Schizophrenia Research 01/2013; DOI:10.1016/j.schres.2013.01.004 · 4.43 Impact Factor
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    ABSTRACT: BACKGROUND: 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. Method 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. RESULTS: 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. CONCLUSIONS: Aberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.
    Psychological Medicine 11/2012; 43(8):1-12. DOI:10.1017/S0033291712002541 · 5.43 Impact Factor
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    ABSTRACT: Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG). While these findings helped to understand the neural underpinnings of hearing voices, they provide little information about possible brain mechanisms that predispose a person to experience AVH, i.e. the traits to hallucinate. In this study, we compared resting state connectivity between 49 psychotic patients with chronic AVH and 49 matched controls using the rIFG and the lSTG as seed regions, to identify functional brain systems underlying the predisposition to hallucinate. The right parahippocampal gyrus showed increased connectivity with the rIFG in patients as compared to controls. Reduced connectivity with the rIFG in patients was found for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG in patients was identified in the left frontal operculum as well as the parietal opercular area. Connectivity between the lSTG and the left hippocampus was also reduced in patients and showed a negative correlation with the severity of hallucinations. Concluding, we found aberrant connectivity between the seed regions and medial temporal lobe structures which have a prominent role in memory retrieval. Moreover, we found decreased connectivity between language-related areas, indicating aberrant integration in this system potentially including corollary discharge mechanisms.
    PLoS ONE 09/2012; 7(9):e43516. DOI:10.1371/journal.pone.0043516 · 3.53 Impact Factor
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    ABSTRACT: Background Auditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology. Methods Twelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism. Results AVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus. Conclusions These results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself.
    PLoS ONE 07/2012; 7(7-7). DOI:10.1371/journal.pone.0041149 · 3.53 Impact Factor
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    Kelly Maria Johanna Diederen, Remko van Lutterveld, Iris E C Sommer
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    ABSTRACT: Auditory verbal hallucinations (AVH) or "voices" are a characteristic symptom of schizophrenia, but can also be observed in healthy individuals in the general population. As these non-psychotic individuals experience AVH in the absence of other psychiatric symptoms and medication-use they provide an excellent model to study AVH in isolation. Indeed a number of studies used this approach and investigated brain structure and function in non-psychotic individuals with AVH. These studies showed that increased sensitivity of auditory areas to auditory stimulation and aberrant connectivity of language production and perception areas is associated with AVH. This is in concordance with investigations that observed prominent activation of these areas during the state of AVH. Moreover, while effortful attention appears not to be related to AVH, individuals prone to hallucinate seem to have an enhanced attention bias to auditory stimuli which may stem from aberrant activation of the anterior cingulated regions. Furthermore, it was observed that decreased cerebral dominance for language and dopamine dysfunction, which are consistently found in schizophrenia, are most likely not specifically related to AVH as these abnormalities were absent in healthy voice hearers. Finally, specific aspects of AVH such as voluntary control may be related to the timing of the supplementary motor area and language areas in the experience of AVH.
    Frontiers in Human Neuroscience 05/2012; 6:111. DOI:10.3389/fnhum.2012.00111 · 2.90 Impact Factor
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    ABSTRACT: BACKGROUND: Hallucinations have consistently been associated with traumatic experiences during childhood. This association appears strongest between physical and sexual abuse and auditory verbal hallucinations (AVH). It remains unclear whether traumatic experiences mainly colour the content of AVH or whether childhood trauma triggers the vulnerability to experience hallucinations in general. In order to investigate the association between hallucinations, childhood trauma and the emotional content of hallucinations, experienced trauma and phenomenology of AVH were investigated in non-psychotic individuals and in patients with a psychotic disorder who hear voices.MethodA total of 127 non-psychotic individuals with frequent AVH, 124 healthy controls and 100 psychotic patients with AVH were assessed for childhood trauma. Prevalence of childhood trauma was compared between groups and the relation between characteristics of voices, especially emotional valence of content, and childhood trauma was investigated. RESULTS: Both non-psychotic individuals with AVH and patients with a psychotic disorder and AVH experienced more sexual and emotional abuse compared with the healthy controls. No difference in the prevalence of traumatic experiences could be observed between the two groups experiencing AVH. In addition, no type of childhood trauma could distinguish between positive or negative emotional valence of the voices and associated distress. No correlations were found between sexual abuse and emotional abuse and other AVH characteristics. CONCLUSIONS: These results suggest that sexual and emotional trauma during childhood render a person more vulnerable to experience AVH in general, which can be either positive voices without associated distress or negative voices as part of a psychotic disorder.
    Psychological Medicine 04/2012; 42(12):1-10. DOI:10.1017/S0033291712000761 · 5.43 Impact Factor
  • Schizophrenia Research 04/2012; 136:S293. DOI:10.1016/S0920-9964(12)70868-X · 4.43 Impact Factor
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    ABSTRACT: Auditory verbal hallucinations (AVH) in patients with borderline personality disorder (BPD) are frequently claimed to be brief, less severe and qualitatively different from those in schizophrenia, hence the term 'pseudohallucinations'. AVH in BPD may be more similar to those experienced by healthy individuals, who experience AVH in a lower frequency and with a more positive content than AVH in schizophrenia. In this study the phenomenology of AVH in BPD patients was compared to that in schizophrenia and to AVH experienced by non-patients. In a cross-sectional setting, the phenomenological characteristics of AVH in 38 BPD patients were compared to those in 51 patients with schizophrenia/schizoaffective disorder and to AVH of 66 non-patients, using the Psychotic Symptom Rating Scales (PSYRATS). BPD patients experienced AVH for a mean duration of 18 years, with a mean frequency of at least daily lasting several minutes or more. The ensuing distress was high. No differences in the phenomenological characteristics of AVH were revealed among patients diagnosed with BPD and those with schizophrenia/schizoaffective disorder, except for 'disruption of life', which was higher in the latter group. Compared to non-patients experiencing AVH, BPD patients had higher scores on almost all items. AVH in BPD patients are phenomenologically similar to those in schizophrenia, and different from those in healthy individuals. As AVH in patients with BPD fulfil the criteria of hallucinations proper, we prefer the term AVH over 'pseudohallucinations', so as to prevent trivialization and to promote adequate diagnosis and treatment.
    Psychological Medicine 02/2012; 42(9):1873-8. DOI:10.1017/S0033291712000165 · 5.43 Impact Factor
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    ABSTRACT: Background:The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations.Methods:We compared dopamine synthesis capacity (using 6-[(18)F]fluoro-L-DOPA [[(18)F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls.Results:There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group.Conclusions:Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.
    Schizophrenia Bulletin 01/2012; DOI:10.1093/schbul/sbr195 · 8.61 Impact Factor
  • I. Sommer, K. M. J. Diederen, S. W. Neggers, R. S. Kahn
    European Neuropsychopharmacology 09/2011; 21. DOI:10.1016/S0924-977X(11)70277-2 · 5.40 Impact Factor

Publication Stats

600 Citations
212.01 Total Impact Points

Institutions

  • 2010–2014
    • University Medical Center Utrecht
      • Department of Psychiatry
      Utrecht, Utrecht, Netherlands
    • National Scientific and Technical Research Council
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2013
    • University of Cambridge
      • Department of Physiology, Development and Neuroscience
      Cambridge, England, United Kingdom
  • 2011
    • Parnassia Bavo Groep
      's-Gravenhage, South Holland, Netherlands