About psychotic-like experiences and auditory verbal hallucinations : Transdiagnostic investigations of neurobiological, cognitive, and emotional aspects of a continuous phenomenon

Hallucinations and delusions are known to be key symptoms of psychotic disorders, such as schizophrenia, and have been studied extensively. However, these experiences also occur in other mental disorders, which suggests a transdiagnostic perspective with shared underlying cognitive mechanisms across various psychological illnesses. In addition, hallucinations and delusions are continuous phenomena that occur not only in patients with mental disorders, but also in healthy individuals in the general population, spanning from childhood to adulthood. To understand the development and maintenance of such psychotic-like experiences (PLEs) in general, and auditory verbal hallucinations (AVHs) specifically, neurobiological, cognitive, and emotional factors need to be taken into consideration. The aim of this thesis is to examine these factors by investigating underlying brain mechanisms of inner speech processes, the impact of emotions, and core schemas about the self and others in different groups of individuals along the continuum from healthy individuals to voice hearers with different underlying disorders. In paper 1, we investigated PLEs in Norway in a sample from the general population, using the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders, with childhood experiences being rather low. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, we revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of paper 1 support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. In paper 2, we investigated neurobiological factors of cognitive inner speech processes by using a neurostimulation method called transcranial direct current stimulation (tDCS) to modulate source monitoring abilities in healthy individuals. We modulated reality monitoring (distinguishing between external and internal sources) and internal source monitoring abilities (distinguishing between two or more internal sources). We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation. Our findings suggest that there are different brain areas involved in reality and internal source monitoring: Internal source monitoring seems to involve Broca’s area. Reality monitoring, however, seems to rely more on the superior temporal gyrus (STG) and the dorsolateral prefrontal cortex (DLPFC) as shown in other studies. In paper 3, we focused on cognitive and emotional aspects of AVHs, namely the impact of emotions and affect on AVH phenomenology in non-clinical and different clinical populations. Depending on the underlying psychopathology, these phenomena show different phenomenological aspects. Our aim was to determine the mediating roles of anxiety and depression in the relationship between positive and negative core schemas about the self and others, and emotional aspects of AVHs for three groups: non clinical voice hearers, affective voice hearers, and non-affective voice hearers. Results showed full mediating effects of anxiety in affective voice hearers in the relationship between negative core schemas and all phenomenological aspects, but not in non-affective voice hearers. Depression was not a mediator in any of the groups. These findings suggest different emotional mechanisms for different groups of voice hearers, depending on the underlying psychopathology of individuals with AVHs. Overall, we conclude that the findings support a continuous and transdiagnostic perspective of PLEs in general, and AVHs specifically. However, more integrative transdiagnostic investigations in different groups of individuals along the continuum are needed as studying AVHs in only one modality or one clinical population is unlikely to bring us closer to understanding how these phenomena develop in the first place.Doktorgradsavhandlin

Transcranial direct current stimulation (tDCS) enhances internal source monitoring abilities in healthy participants

Source monitoring refers to the ability to identify the origin of a memory, for example, whether you remember saying something or thinking about it, and confusions of these sources have been associated with the experience of auditory verbal hallucinations (AVHs). Both AVHs and source confusions are reported to originate from dysfunctional brain activations in the prefrontal cortex (PFC) and the superior temporal gyrus (STG); specifically, it is assumed that a hypoactive PFC and a hyperactive STG gives rise to AVHs and source confusions. We set out to test this assumption by trying to mimic this hypertemporal/hypofrontal model in healthy individuals with transcranial direct current stimulation (tDCS): the inhibitory cathode was placed over the left PFC and the excitatory anode over the left dorsolateral STG. Participants completed a reality monitoring task (distinguishing between external and internal memory sources) and an internal source monitoring task (distinguishing between two or more internal memory sources) in two separate experiments (offline vs. online tDCS). In the offline experiment (n = 34), both source monitoring tasks were completed after tDCS stimulation, and in the online experiment (n = 27) source monitoring tasks were completed while simultaneously being stimulated with tDCS. We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation in both experiments. We speculate, based on combining the present findings with previous studies, that there might be different brain areas involved in reality and internal source monitoring. While internal source monitoring seems to involve speech production areas, specifically Broca’s area, as suggested in the present study, reality monitoring seems to rely more on the STG and DLPFC, as shown in other studies of the field.publishedVersio

A multimodal study of the effects of tDCS on dorsolateral prefrontal and temporo-parietal areas during dichotic listening

The underlying neural mechanisms of transcranial direct current stimulation (tDCS), especially beyond the primary motor cortex, remain unclear. Several studies examined tDCS effects on either functional activity, neurotransmitters or behavior but few investigated those aspects together to reveal how the brain responds to tDCS. The objective is to elucidate the underlying mechanisms of tDCS using a multimodal approach that extends from behavioral to neurotransmitter levels of explanation. Thirty‐two healthy participants performed an auditory dichotic listening task at two visits, one session with sham and one session with real tDCS (2 mA) while simultaneously undergoing functional magnetic resonance imaging (fMRI). The anode and cathode were placed over the left temporo‐parietal cortex (TPC) and dorsolateral prefrontal cortex, respectively. Before and after simultaneous dichotic listening/fMRI/tDCS, combined glutamate and glutamine (Glx) and myo‐inositol levels were assessed in the stimulated areas. While fMRI and dichotic listening showed expected functional activity and behavioral effects, neither method demonstrated differences between real and sham stimulation. Glx only showed a statistical trend towards higher levels after real tDCS in both stimulated brain areas. There were no significant correlations between behavior and Glx. Despite a reasonable sample size, electrical field strength, and replication of behavioral and functional activity results, tDCS had little to no effect on dichotic listening, Glx, and functional activity. The study emphasizes that findings about the underlying neural mechanisms of the primary motor cortex cannot simply be generalized to other brain areas. Particularly, the TPC might be less sensitive to tDCS. Moreover, the study demonstrates the general feasibility of multimodal approaches

Pilot-RCT Finds No Evidence for Modulation of Neuronal Networks of Auditory Hallucinations by Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is used as treatment for auditory verbal hallucinations (AVH). The theory behind the treatment is that tDCS increases activity in prefrontal cognitive control areas, which are assumed to be hypoactive, and simultaneously decreases activity in temporal speech perception areas, which are assumed to be hyperactive during AVH. We tested this hypofrontal/hypertemporal reversal theory by investigating anatomical, neurotransmitter, brain activity, and network connectivity changes over the course of tDCS treatment. Methods: A double-blind, randomized controlled trial was conducted with 21 patients receiving either sham or real tDCS treatment (2 mA) twice daily for 5 days. The anode was placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the left temporo-parietal cortex (TPC). Multimodal neuroimaging as well as clinical and neurocognitive functioning assessment were performed before, immediately after, and three months after treatment. Results: We found a small reduction in AVH severity in the real tDCS group, but no corresponding neuroimaging changes in either DLPFCD or TPC. Limitations: The study has a small sample size. Conclusion: The results suggest that the currently leading theory behind tDCS treatment of AVH may need to be revised, if confirmed by studies with larger N. Tentative findings point to the involvement of Broca’s area as a critical structure for tDCS treatment.publishedVersio

Pilot-RCT Finds No Evidence for Modulation of Neuronal Networks of Auditory Hallucinations by Transcranial Direct Current Stimulation

Background: Transcranial direct current stimulation (tDCS) is used as treatment for auditory verbal hallucinations (AVH). The theory behind the treatment is that tDCS increases activity in prefrontal cognitive control areas, which are assumed to be hypoactive, and simultaneously decreases activity in temporal speech perception areas, which are assumed to be hyperactive during AVH. We tested this hypofrontal/hypertemporal reversal theory by investigating anatomical, neurotransmitter, brain activity, and network connectivity changes over the course of tDCS treatment. Methods: A double-blind, randomized controlled trial was conducted with 21 patients receiving either sham or real tDCS treatment (2 mA) twice daily for 5 days. The anode was placed over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the left temporo-parietal cortex (TPC). Multimodal neuroimaging as well as clinical and neurocognitive functioning assessment were performed before, immediately after, and three months after treatment. Results: We found a small reduction in AVH severity in the real tDCS group, but no corresponding neuroimaging changes in either DLPFCD or TPC. Limitations: The study has a small sample size. Conclusion: The results suggest that the currently leading theory behind tDCS treatment of AVH may need to be revised, if confirmed by studies with larger N. Tentative findings point to the involvement of Broca’s area as a critical structure for tDCS treatment.publishedVersio

About psychotic-like experiences and auditory verbal hallucinations : Transdiagnostic investigations of neurobiological, cognitive, and emotional aspects of a continuous phenomenon

Hallucinations and delusions are known to be key symptoms of psychotic disorders, such as schizophrenia, and have been studied extensively. However, these experiences also occur in other mental disorders, which suggests a transdiagnostic perspective with shared underlying cognitive mechanisms across various psychological illnesses. In addition, hallucinations and delusions are continuous phenomena that occur not only in patients with mental disorders, but also in healthy individuals in the general population, spanning from childhood to adulthood. To understand the development and maintenance of such psychotic-like experiences (PLEs) in general, and auditory verbal hallucinations (AVHs) specifically, neurobiological, cognitive, and emotional factors need to be taken into consideration. The aim of this thesis is to examine these factors by investigating underlying brain mechanisms of inner speech processes, the impact of emotions, and core schemas about the self and others in different groups of individuals along the continuum from healthy individuals to voice hearers with different underlying disorders. In paper 1, we investigated PLEs in Norway in a sample from the general population, using the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders, with childhood experiences being rather low. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, we revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of paper 1 support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. In paper 2, we investigated neurobiological factors of cognitive inner speech processes by using a neurostimulation method called transcranial direct current stimulation (tDCS) to modulate source monitoring abilities in healthy individuals. We modulated reality monitoring (distinguishing between external and internal sources) and internal source monitoring abilities (distinguishing between two or more internal sources). We found that internal source monitoring abilities were significantly enhanced during active online tDCS, while reality monitoring abilities were unaffected by stimulation. Our findings suggest that there are different brain areas involved in reality and internal source monitoring: Internal source monitoring seems to involve Broca’s area. Reality monitoring, however, seems to rely more on the superior temporal gyrus (STG) and the dorsolateral prefrontal cortex (DLPFC) as shown in other studies. In paper 3, we focused on cognitive and emotional aspects of AVHs, namely the impact of emotions and affect on AVH phenomenology in non-clinical and different clinical populations. Depending on the underlying psychopathology, these phenomena show different phenomenological aspects. Our aim was to determine the mediating roles of anxiety and depression in the relationship between positive and negative core schemas about the self and others, and emotional aspects of AVHs for three groups: non clinical voice hearers, affective voice hearers, and non-affective voice hearers. Results showed full mediating effects of anxiety in affective voice hearers in the relationship between negative core schemas and all phenomenological aspects, but not in non-affective voice hearers. Depression was not a mediator in any of the groups. These findings suggest different emotional mechanisms for different groups of voice hearers, depending on the underlying psychopathology of individuals with AVHs. Overall, we conclude that the findings support a continuous and transdiagnostic perspective of PLEs in general, and AVHs specifically. However, more integrative transdiagnostic investigations in different groups of individuals along the continuum are needed as studying AVHs in only one modality or one clinical population is unlikely to bring us closer to understanding how these phenomena develop in the first place

Die Rolle der Angst bei Kontrollüberzeugungen

Die vorliegende Arbeit beschäftigt sich mit den komplexen Verbindungen zwischen Kon-trollüberzeugungen, Depression und der Angst als Emotion. Gegenstand der Untersu-chung war zum einen die Verarbeitung von Angst bei depressiv Erkrankten und zum an-deren der Zusammenhang mit den verschiedenen Ausprägungen der Kontrollüberzeugun-gen. Kontrollüberzeugungen können entweder internal oder external ausgerichtet sein. Dies bedeutet, dass die Kontrolle über wichtige Ereignisse im Leben entweder sich selbst oder anderen Faktoren und/oder Personen zugeschrieben wird. Die insgesamt vierzig UntersuchungsteilnehmerInnen wurden gebeten, sich in angstbe-haftete und neutrale Sätze hineinzuversetzen, die visuell präsentiert wurden. Zusätzlich zur funktionellen Magnetresonanztomographie wurden neuropsychologische Fragebo-genverfahren angewendet. Es fanden sich signifikante Zusammenhänge zwischen den Ausprägungen der Kontroll-überzeugung einerseits mit der Depressionsausprägung und andererseits mit der Angst-ausprägung. Bei der Konstanthaltung der Emotion Angst ließ sich keine Tendenz ausma-chen, dass der Zusammenhang zwischen Depressionsausprägung und Kontrollüberzeu-gung zusätzlich durch die Angstausprägung beeinflusst wird. Neurologisch zeigten sich angstbezogene Hirnaktivierungen im frontal-inferioren und temporal-superioren Bereich des Gehirns. Die neutrale Bedingung aktiviert zusätzlich zu medialen Bereichen im Frontal- und Okzipitallappen auch Regionen des Parietallappens und das limbische System. Die Ergebnisse werden in Bezug auf bisherige Befunde diskutiert.This thesis examined the complex relations between locus of control reinforcement, de-pression and fear as emotion. On the one hand the subject of the study was the neuronal processing of depressed patients. On the other hand the connection and correlation with the different occurrences of locus of control reinforcement were analyzed. The latter are either internal or external. This means an attribution of control about important events in people’s lifes to themselves or to other external factors (e.g. luck or other people). Overall 40 people participated. They were asked to put themselves in fearful or neutral situations. Stimuli were presented visually, while they had an fMRI exploration. Addi-tionally neuropsychological questionnaires had to be completed. There were significant correlations between locus of control reinforcement with both de-pression and fear. When controlling the effect of fear, the significant correlation between locus of control reinforcement and depression disappeared. In the fearful condition fronto-inferior and temporo-superior areas were activated. The neutral condition activated medial areas in the frontal and occipital lobe, and also regions of the parietal and limbic lobe. Findings are discussed in relation to previous results

An online survey on clinical and healthy individuals with auditory verbal hallucinations: Abuse did not lead to more negative voice content.

peer reviewedDespite the clinical and theoretical importance of the negative content in auditory verbal hallucinations (AVHs), little research has been conducted on the topic. A handful of studies suggest that trauma or adverse life events contribute to negative content. The findings are somewhat inconsistent, however, possibly due to methodological limitations. Moreover, only trauma occurring in childhood has been investigated so far. In the present study, we studied the effect of abuse, experienced in either child- or adulthood, and clinical status on negative content of AVHs in four groups of participants that were assessed as part of a large, previously published online survey: Individuals with a psychotic disorder and AVHs (total n = 33), who had experienced abuse (n = 21) or not (n = 12) as well as a group of healthy individuals with AVHs (total n = 53), who had experienced abuse (n = 31) or not (n = 22). We hypothesized that having experienced abuse was associated with a higher degree of negative content. The clinical group collectively reported significantly higher degrees of negative AVHs content compared to the healthy group, but there was no effect of abuse on the degree of negative AVHs content. The presence of AVHs was more common amongst individuals who reported a history of abuse compared to individuals with no history of abuse, both in clinical and healthy participants with AVHs. This implies that at group level, being subjected to traumatic events increases an individual's vulnerability to experiencing AVHs. However, it does not necessarily account for negative content in AVHs