The aim of this study was to explore the experience of hearing voices in the general New Zealand adult population. This included mapping the topography of voices and the impact of the experience on participants’ lives, exploring participants’ explanatory models, investigating coping strategies and support structures, and developing a model of the essence of hearing voices. Quantitative and qualitative analyses of questionnaire (n=154) and interview (n=50) data revealed a great diversity of experiences, both within and among participants. Of all topographical variables significantly related to emotional impact (content, form, duration, intrusiveness and control), voice content was the only significant predictor variable, accurately predicting the emotional response of 93.3% of participants. Overall, participants who valued their voice experiences tended to have spiritual beliefs, a more positive emotional reaction and less contact with mental health services. In contrast, participants who experienced mostly unwanted voices tended to have biological and/or psychological understandings of their voice experiences, a more negative emotional reaction to them, and increased contact with mental health services. Participants reported using a vast array of coping strategies, with varying degrees of success. Individualised techniques were reported to be the most effective, followed by setting aside a time to listen to the voices. In terms of help and support, participants called for a model of intervention that accepted their voice experiences as real, took an holistic approach incorporating contextual, cultural and spiritual factors, and worked with voice-hearers, their families and the public to provide information about voice phenomena and normalise the experience. Using a phenomenological approach, a model of the essential structure of hearing voices is proposed, comprising five components: the content of the voices is personally meaningful to the voice-hearer; the voices have a characterised identity; the person has a relationship with their voices; the experience has a significant impact on the voice-hearer’s life; and the experience has a compelling sense of reality. The implications of this research include validating voice-hearers’ perspectives of the experience, informing clinical work with voice-hearers, and informing the development of local and national-level services, such as a New Zealand Hearing Voices Network.

The aim of this study was to explore the experience of hearing voices in the general New Zealand adult population. This included mapping the topography of voices and the impact of the experience on participants’ lives, exploring participants’ explanatory models, investigating coping strategies and support structures, and developing a model of the essence of hearing voices. Quantitative and qualitative analyses of questionnaire (n=154) and interview (n=50) data revealed a great diversity of experiences, both within and among participants. Of all topographical variables significantly related to emotional impact (content, form, duration, intrusiveness and control), voice content was the only significant predictor variable, accurately predicting the emotional response of 93.3% of participants. Overall, participants who valued their voice experiences tended to have spiritual beliefs, a more positive emotional reaction and less contact with mental health services. In contrast, participants who experienced mostly unwanted voices tended to have biological and/or psychological understandings of their voice experiences, a more negative emotional reaction to them, and increased contact with mental health services. Participants reported using a vast array of coping strategies, with varying degrees of success. Individualised techniques were reported to be the most effective, followed by setting aside a time to listen to the voices. In terms of help and support, participants called for a model of intervention that accepted their voice experiences as real, took an holistic approach incorporating contextual, cultural and spiritual factors, and worked with voice-hearers, their families and the public to provide information about voice phenomena and normalise the experience. Using a phenomenological approach, a model of the essential structure of hearing voices is proposed, comprising five components: the content of the voices is personally meaningful to the voice-hearer; the voices have a characterised identity; the person has a relationship with their voices; the experience has a significant impact on the voice-hearer’s life; and the experience has a compelling sense of reality. The implications of this research include validating voice-hearers’ perspectives of the experience, informing clinical work with voice-hearers, and informing the development of local and national-level services, such as a New Zealand Hearing Voices Network.

[Truncated abstract] Auditory hallucinations are some of the most distressing and disabling symptoms of schizophrenia. However very little is known about the exact processes responsible for auditory hallucinations. The aim of this thesis is to provide a new perspective on the nature of the cognitive deficits underlying auditory hallucinations in schizophrenia. As a preliminary study to the investigation of auditory hallucinations in schizophrenia, a factor analysis of a measure of hallucinatory predisposition, the Launay- Slade Hallucination Scale-Revised (Bentall & Slade, 1985), was carried out on data from a large sample of undergraduate students (N = 562). An overlap in characteristics between hallucinatory-like experiences in normal individuals and auditory hallucinations in schizophrenia should draw attention to factors that are important to the hallucinatory experience in general. One of the findings from this study was that intrusiveness is a commonly reported characteristic of hallucinatory-like experiences in normal individuals. Intrusiveness is also one of the defining features of auditory hallucinations in schizophrenia. Since the process of inhibition is essential for suppressing unwanted thoughts, the first set of two studies using patients with schizophrenia (N = 43) investigated the presence of an (intentional) inhibition failure in auditory hallucinations using the Hayling Sentence Completion Test (HSCT; Burgess & Shallice, 1996) and the Inhibition of Currently Irrelevant Memories Task (ICIM; Schnider & Ptak, 1999). It was found that auditory hallucinations were linked to a deficit in intentional inhibition as measured by these tasks. The process of inhibition was further investigated using the Affective Shifting task, but auditory hallucinations were not associated with a deficit on this task. Possible differences in the inhibitory demands of the HSCT, ICIM and Affective Shifting tasks are discussed.

The aim of this study was to explore the experience of hearing voices in the general New Zealand adult population. This included mapping the topography of voices and the impact of the experience on participants’ lives, exploring participants’ explanatory models, investigating coping strategies and support structures, and developing a model of the essence of hearing voices. Quantitative and qualitative analyses of questionnaire (n=154) and interview (n=50) data revealed a great diversity of experiences, both within and among participants. Of all topographical variables significantly related to emotional impact (content, form, duration, intrusiveness and control), voice content was the only significant predictor variable, accurately predicting the emotional response of 93.3% of participants. Overall, participants who valued their voice experiences tended to have spiritual beliefs, a more positive emotional reaction and less contact with mental health services. In contrast, participants who experienced mostly unwanted voices tended to have biological and/or psychological understandings of their voice experiences, a more negative emotional reaction to them, and increased contact with mental health services. Participants reported using a vast array of coping strategies, with varying degrees of success. Individualised techniques were reported to be the most effective, followed by setting aside a time to listen to the voices. In terms of help and support, participants called for a model of intervention that accepted their voice experiences as real, took an holistic approach incorporating contextual, cultural and spiritual factors, and worked with voice-hearers, their families and the public to provide information about voice phenomena and normalise the experience. Using a phenomenological approach, a model of the essential structure of hearing voices is proposed, comprising five components: the content of the voices is personally meaningful to the voice-hearer; the voices have a characterised identity; the person has a relationship with their voices; the experience has a significant impact on the voice-hearer’s life; and the experience has a compelling sense of reality. The implications of this research include validating voice-hearers’ perspectives of the experience, informing clinical work with voice-hearers, and informing the development of local and national-level services, such as a New Zealand Hearing Voices Network.

abstract: ABSTRACT Auditory hallucinations are a characteristic symptom of schizophrenia. Research has documented that the auditory cortex is metabolically activated when this process occurs, and that imbalances in the dopaminergic transmission in the striatum contribute to its physiopathology. Most animal models have focused the effort on pharmacological approaches like non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists to produce activation of the auditory cortex, or dopamine antagonists to alleviate it. I hypothesize that these perceptual phenomena can be explained by an imbalance activation of spiny projecting neurons in the striatal pathways, whereby supersensitive postsynaptic D2-like receptor, signaling in the posterior caudatoputamen generates activation of the auditory cortex. Therefore, I characterized the neuroanatomical component involved in the activation of the auditory cortex. I evaluated the participation of dopamine D2-like receptor using selective dopamine antagonist manipulations and identified the circuits related to the auditory cortex by retrograde trans-synaptic tracing using pseudorabies virus (PRV-152). My results show that dopamine infused in the posterior caudatoputamen dose dependently increases the transcription of the immediate early gene, zif268 in the auditory cortex, predominantly in layers III and IV, but also in cortical columns, suggesting enhanced functional auditory activity. This indicates the participation of the posterior striatum in the modulation of the secondary auditory cortex. I was able to demonstrate also that a coinfusion of a selective dopamine D2-like receptor antagonist, eticlopride and dopamine, attenuate the activation of the auditory cortex. Furthermore, using PRV-152 I delineate the distinctive circuit by axial mapping of the infected neurons. Thus, I found secondary projections from the posterior caudatoputamen that synapse in the thalamus before reaching the auditory cortex. These striatal projections correspond to the same brain region affected by dopamine during auditory cortical activation. My results further characterized a mechanism to generate intrinsic perception of sound that may be responsible for auditory hallucinations. I propose this paradigm may elucidate insight on the biological basis of psychotic behavior. / Dissertation/Thesis / Figure 9C. 3D brain reconstruction after 48 hours of PRV-152 inoculations / Figure 9A. 3D brain reconstruction after 24 h postinoculation / Figure 9B. 3D brain reconstruction after 36 h postinoculation / Doctoral Dissertation Neuroscience 2014

Hearing voices is a well researched experience, found in both schizophrenia and the general population. Previous research investigating the unusual experience has reinforced cognitive psychology concepts such as beliefs, power, core beliefs about the self, intent and identity. It has been suggested that these factors all mediate individual coping with the experience. Coping with voices is a clinically significant area of research pioneered by Romme and Escher and requires careful consideration. Kelly‘s Personal Construct Psychology and the repertory grid technique were used in the study to compare two ways of coping with voices: engaging and resisting coping. The groups were compared on the repertory grid measures of construed distance between the self and the voice, salience of the self and voice, and tightness of the overall construct system. In a sample of 18 voice hearers, the Beliefs about Voices Questionnaire- Revised (BAVQ-R), a measure of psychological distress (OQ45.2) and Kelly‘s repertory grid were administered. The study also used three case examples and content analysis of construct poles applied to the dominant voice and the self as coper to supplement the quantitative analysis with a more in-depth exploration. Resisting coping was found to be associated with a greater construed distance between the self and the voice, a more salient view of the voice, and a tighter construct system. However, neither resisting nor engaging coping was associated with psychological distress. In addition, voice malevolence was associated with distancing oneself from the voice, suggesting that distancing was an adaptive coping strategy used, possibly as a way to preserve selfhood. The study therefore added to the list of mediating factors between the voice hearing experience and the coping strategy adopted. As a result, the repertory grid showed some scope in assessing the three areas of interest. The findings suggest that clinically, voice hearers can best be supported by adopting the appropriate relational approach with the voice (closeness or distance), reducing the salience of the voice and moving through Kelly‘s Creativity and Experience Cycle.

Les hallucinations auditives verbales (HAVs) sont des perceptions langagières en l'absence de stimuli externes appropriés. Elles sont un des symptômes les plus invalidants dans la schizophrénie. Parmi les grands types de modèles explicatifs, deux sont particulièrement intéressants : les modèles à origine perceptive, selon lesquels les voix entendues seraient dues à une imagerie mentale et des représentations auditives trop vives et les modèles à origine productive, selon lesquels la parole intérieure est perturbée de telle sorte que les propres pensées verbales du patient sont attribuées à un agent externe. Pour tester le versant moteur des modèles productifs, une expérience de recueil de traces oro-faciales lors des HAVs à l'aide de l'électromyographie de surface a été conduite auprès de 11 patients schizophrènes. Les résultats montrent une tendance à l'augmentation de l'activité musculaire de l'orbiculaire inférieur lors des HAVs par rapport à une condition de repos. Pour tester le versant cérébral des modèles, une expérience en IRMf de génération de pensée verbale et de perception auditive a été menée auprès de 19 sujets schizophrènes et 24 sujets contrôles et a montré une hyper-activation d'un réseau impliquant le cortex temporal et le cortex cingulaire antérieur. La caractérisation phénoménologique des HAVs vécues par les patients a montré que les HAVs diffèrent de la pensée intérieure typique en ce que les voix entendues peuvent être nombreuses et ne sont pas celle du patient lui-même. Ainsi aucun des deux types de modèles considérés isolément n'est satisfaisant pour expliquer les HAVs. Un modèle intégratif multidimensionnel permettrait de mieux rendre compte de la complexité des HAVs. Il existerait, chez les patients schizophrènes une prédisposition perceptive hyper-active couplée à un système de prédiction défaillant. Les deux dysfonctionnements seraient de plus modulés par des facteurs top-down, de stress et un biais cognitif d'externalisation. / Les hallucinations auditives verbales (HAVs) sont des perceptions langagières en l'absence de stimuli externes appropriés. Elles sont un des symptômes les plus invalidants dans la schizophrénie. Parmi les grands types de modèles explicatifs, deux sont particulièrement intéressants : les modèles à origine perceptive, selon lesquels les voix entendues seraient dues à une imagerie mentale et des représentations auditives trop vives et les modèles à origine productive, selon lesquels la parole intérieure est perturbée de telle sorte que les propres pensées verbales du patient sont attribuées à un agent externe. Pour tester le versant moteur des modèles productifs, une expérience de recueil de traces oro-faciales lors des HAVs à l'aide de l'électromyographie de surface a été conduite auprès de 11 patients schizophrènes. Les résultats montrent une tendance à l'augmentation de l'activité musculaire de l'orbiculaire inférieur lors des HAVs par rapport à une condition de repos. Pour tester le versant cérébral des modèles, une expérience en IRMf de génération de pensée verbale et de perception auditive a été menée auprès de 19 sujets schizophrènes et 24 sujets contrôles et a montré une hyper-activation d'un réseau impliquant le cortex temporal et le cortex cingulaire antérieur. La caractérisation phénoménologique des HAVs vécues par les patients a montré que les HAVs diffèrent de la pensée intérieure typique en ce que les voix entendues peuvent être nombreuses et ne sont pas celle du patient lui-même. Ainsi aucun des deux types de modèles considérés isolément n'est satisfaisant pour expliquer les HAVs. Un modèle intégratif multidimensionnel permettrait de mieux rendre compte de la complexité des HAVs. Il existerait, chez les patients schizophrènes une prédisposition perceptive hyper-active couplée à un système de prédiction défaillant. Les deux dysfonctionnements seraient de plus modulés par des facteurs top-down, de stress et un biais cognitif d'externalisation.

Introdução: Esquizofrenia é um distúrbio psicótico complexo e heterogêneo. Alucinações auditivas verbais ocorrem em 50% a 70% dos pacientes portadores de esquizofrenia, e estão associadas a prejuízo significativo, pior qualidade de vida e funcionamento social. Estudos prévios mostraram que a estimulação magnética transcraniana repetida (EMTr) parece ser capaz de modular a severidade das alucinações auditivas em pacientes com esquizofrenia. Este estudo investigou os efeitos da rTMS de 1Hz aplicada ao córtex temporoparietal esquerdo, comparada a estimulação sham, na psicopatologia geral, severidade das alucinações auditivas, qualidade de vida e funcionalidade. Métodos: Dezessete pacientes apresentando alucinações auditivas verbais pelo menos cinco vezes ao dia forma randomicamente distribuídos para receber EMTr ativa ou sham. Um total de 384 minutos de EMTr a 90% do limiar motor foram administrados ao longo de 20 dias usando um desenho paralelo, duplo-cego e controlado por placebo. Resultados: Houve um efeito positivo nos escores da BPRS no grupo ativo comparado ao grupo sham. Não houve diferenças significativas entre os grupos no final do tratamento nos escores da QLS, AHRS, CGI e FAST. Conclusões: Comparada a estimulação sham, a EMTr do cortex temporoparietal esquerdo mostrou um efeito positivo na psicopatologia geral. Novos estudos com tamanhos de amostra maiores são necessários para investigar efeitos na qualidade de vida e funcionalidade, uma vez que o poder deste estudo foi menor que 50%. Além disso, seu efeito em alucinações auditivas refratárias não é claro, uma vez que os escores de alucinações auditivas globais e individuais não foram diferentes. / Background: Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50% to 70% of patients with schizophrenia, and are associated to significant distress, decreased quality of life and social functioning. Data from previous studies have shown that 1-hertz left temporo-parietal repetitive transcranial magnetic stimulation (rTMS) appears to be able to modulate the severity of auditory hallucinations in patients with schizophrenia. This study aimed to investigate the effects of 1 Hz rTMS of the left temporo-parietal cortex on general psychopathology, severity of auditory hallucinations, quality of life and functionality, compared to sham stimulation. Methods: Seventeen patients experiencing auditory verbal hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 384 minutes of rTMS was administered over 20 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. Results: There was a positive effect on BPRS scores on the active group compared to sham group. There was no significant difference between groups at the end of the treatment on QLS, AHRS, CGI and FAST scores. Conclusions: Compared to sham stimulation, rTMS of the left temporo-parietal cortex showed a positive effect on general psychopathology. Further studies with larger sample sizes are needed to investigate effects on quality of life and functionality, since the power of the study was lower than 50%. Also, its effect on refractory auditory hallucinations is not clear, since global and individual scores of auditory hallucinations were not different.

Introdução: Esquizofrenia é um distúrbio psicótico complexo e heterogêneo. Alucinações auditivas verbais ocorrem em 50% a 70% dos pacientes portadores de esquizofrenia, e estão associadas a prejuízo significativo, pior qualidade de vida e funcionamento social. Estudos prévios mostraram que a estimulação magnética transcraniana repetida (EMTr) parece ser capaz de modular a severidade das alucinações auditivas em pacientes com esquizofrenia. Este estudo investigou os efeitos da rTMS de 1Hz aplicada ao córtex temporoparietal esquerdo, comparada a estimulação sham, na psicopatologia geral, severidade das alucinações auditivas, qualidade de vida e funcionalidade. Métodos: Dezessete pacientes apresentando alucinações auditivas verbais pelo menos cinco vezes ao dia forma randomicamente distribuídos para receber EMTr ativa ou sham. Um total de 384 minutos de EMTr a 90% do limiar motor foram administrados ao longo de 20 dias usando um desenho paralelo, duplo-cego e controlado por placebo. Resultados: Houve um efeito positivo nos escores da BPRS no grupo ativo comparado ao grupo sham. Não houve diferenças significativas entre os grupos no final do tratamento nos escores da QLS, AHRS, CGI e FAST. Conclusões: Comparada a estimulação sham, a EMTr do cortex temporoparietal esquerdo mostrou um efeito positivo na psicopatologia geral. Novos estudos com tamanhos de amostra maiores são necessários para investigar efeitos na qualidade de vida e funcionalidade, uma vez que o poder deste estudo foi menor que 50%. Além disso, seu efeito em alucinações auditivas refratárias não é claro, uma vez que os escores de alucinações auditivas globais e individuais não foram diferentes. / Background: Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50% to 70% of patients with schizophrenia, and are associated to significant distress, decreased quality of life and social functioning. Data from previous studies have shown that 1-hertz left temporo-parietal repetitive transcranial magnetic stimulation (rTMS) appears to be able to modulate the severity of auditory hallucinations in patients with schizophrenia. This study aimed to investigate the effects of 1 Hz rTMS of the left temporo-parietal cortex on general psychopathology, severity of auditory hallucinations, quality of life and functionality, compared to sham stimulation. Methods: Seventeen patients experiencing auditory verbal hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 384 minutes of rTMS was administered over 20 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. Results: There was a positive effect on BPRS scores on the active group compared to sham group. There was no significant difference between groups at the end of the treatment on QLS, AHRS, CGI and FAST scores. Conclusions: Compared to sham stimulation, rTMS of the left temporo-parietal cortex showed a positive effect on general psychopathology. Further studies with larger sample sizes are needed to investigate effects on quality of life and functionality, since the power of the study was lower than 50%. Also, its effect on refractory auditory hallucinations is not clear, since global and individual scores of auditory hallucinations were not different.

Introdução: Esquizofrenia é um distúrbio psicótico complexo e heterogêneo. Alucinações auditivas verbais ocorrem em 50% a 70% dos pacientes portadores de esquizofrenia, e estão associadas a prejuízo significativo, pior qualidade de vida e funcionamento social. Estudos prévios mostraram que a estimulação magnética transcraniana repetida (EMTr) parece ser capaz de modular a severidade das alucinações auditivas em pacientes com esquizofrenia. Este estudo investigou os efeitos da rTMS de 1Hz aplicada ao córtex temporoparietal esquerdo, comparada a estimulação sham, na psicopatologia geral, severidade das alucinações auditivas, qualidade de vida e funcionalidade. Métodos: Dezessete pacientes apresentando alucinações auditivas verbais pelo menos cinco vezes ao dia forma randomicamente distribuídos para receber EMTr ativa ou sham. Um total de 384 minutos de EMTr a 90% do limiar motor foram administrados ao longo de 20 dias usando um desenho paralelo, duplo-cego e controlado por placebo. Resultados: Houve um efeito positivo nos escores da BPRS no grupo ativo comparado ao grupo sham. Não houve diferenças significativas entre os grupos no final do tratamento nos escores da QLS, AHRS, CGI e FAST. Conclusões: Comparada a estimulação sham, a EMTr do cortex temporoparietal esquerdo mostrou um efeito positivo na psicopatologia geral. Novos estudos com tamanhos de amostra maiores são necessários para investigar efeitos na qualidade de vida e funcionalidade, uma vez que o poder deste estudo foi menor que 50%. Além disso, seu efeito em alucinações auditivas refratárias não é claro, uma vez que os escores de alucinações auditivas globais e individuais não foram diferentes. / Background: Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50% to 70% of patients with schizophrenia, and are associated to significant distress, decreased quality of life and social functioning. Data from previous studies have shown that 1-hertz left temporo-parietal repetitive transcranial magnetic stimulation (rTMS) appears to be able to modulate the severity of auditory hallucinations in patients with schizophrenia. This study aimed to investigate the effects of 1 Hz rTMS of the left temporo-parietal cortex on general psychopathology, severity of auditory hallucinations, quality of life and functionality, compared to sham stimulation. Methods: Seventeen patients experiencing auditory verbal hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 384 minutes of rTMS was administered over 20 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. Results: There was a positive effect on BPRS scores on the active group compared to sham group. There was no significant difference between groups at the end of the treatment on QLS, AHRS, CGI and FAST scores. Conclusions: Compared to sham stimulation, rTMS of the left temporo-parietal cortex showed a positive effect on general psychopathology. Further studies with larger sample sizes are needed to investigate effects on quality of life and functionality, since the power of the study was lower than 50%. Also, its effect on refractory auditory hallucinations is not clear, since global and individual scores of auditory hallucinations were not different.