Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Anomalies of imagination and development of psychosis: A phenomenological account.

In 20th century psychiatry, various disturbances of imagination were discussed in the context of schizophrenia. Today, these notions have almost completely vanished from mainstream psychopathology. However, recent work has suggested that specific phenomena within this area have a relevance for differential diagnosis and early detection of psychosis. This paper first provides an overview of 20th century psychopathological literature, as well as more recent neurocognitive studies, addressing disturbances of imagination and their role for symptom formation in schizophrenia. It then discusses recent empirical investigations of subjective anomalies of imagination in schizophrenia-spectrum disorders and suggests a clinical-phenomenological account of their role in the development of psychotic symptoms. Empirically and conceptually, these subjective anomalies are linked with disturbances of basic self. Patients' descriptions of the development of their anomalous experiences and symptoms indicate that increased spatial (object-like) articulation and instability of the first-personal manifestation of imaginative experience can be involved in the emergence of delusions and hallucinatory phenomena. Finally, a potential link between subjective anomalies of imagination and the neurocognitive construct of source monitoring deficits is discussed.

Characteristics of Recurrent Visions of the Nonphysical World Among Cognitively Unimpaired Elders of the Ojibwe Tribal Nation.

Importance: Visual hallucinations are a core feature of dementia with Lewy bodies and primary psychiatric disease, yet identification of a hallucination vs normal spiritual experience depends on cultural context. Almost no information exists in the medical literature regarding normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation. Objective: To assess the characteristics of a normal spiritual experience in an Ojibwe Tribal Nation. Design, Setting, and Participants: This prospective, cross-sectional study was conducted between August 1, 2021, and August 31, 2022, among an Ojibwe Tribal Nation in northern Minnesota. Participants were evaluated at their tribal nation clinic. Cognitively unimpaired tribal Elders who were enrolled members of the tribal nation and aged 55 years or older were invited to participate via fliers, radio advertisements, and health fair presentations. Thirty-seven tribal Elders volunteered. Main Outcomes and Measures: Each participant was asked whether they experienced hallucinations or visions of people, animals, or objects that are not part of the physical world. This was an a priori formulated question and part of a comprehensive neurocognitive evaluation consisting of history and physical examination (including cognitive screening with a subspecialty-trained behavioral neurologist); blood tests for metabolic, nutritional, and thyroid conditions; and noncontrast magnetic resonance imaging brain scan. Four patients were excluded from the present analysis due to having mild cognitive impairment or dementia. Results: Thirty-three cognitively unimpaired tribal Elders (mean [SD] age, 66.0 [7.5] years; 22 women [67%]) were included. Sixteen (48%) answered affirmatively, reporting recurrent visions of the nonphysical world. Generally, these visions were well formed, benevolent in nature, and transient; started in preadolescence; involved spirits or ancestors; and were congruent with cultural and spiritual beliefs of the Ojibwe people. No patients had accompanying dream enactment behavior, dysautonomia, parkinsonism, sleep transition-related hallucinations, or moderate to severe depression to suggest a prodrome of an α-synucleinopathy, hypnopompic or hypnagogic hallucinations, or psychosis. Conclusions and Relevance: Although based on only 1 Ojibwe Tribal Nation, this study suggests that formed visions of the nonphysical world are common among cognitively healthy Ojibwe individuals and can represent normal spiritual experiences. Clinicians would benefit from careful consideration of cultural or spiritual context to avoid misdiagnosis of neuropsychiatric disease.

Voice hearers' explanations of trauma-related voices and processes of change throughout imagery rescripting: A qualitative exploration.

OBJECTIVES: Post-traumatic stress is common among people who hear voices (auditory verbal hallucinations), many of whom hear trauma-related voices, whereby voice content is related to past trauma. Preliminary evidence suggests that imagery rescripting (ImRs) may more effectively reduce post-traumatic stress and voices compared to treatments that are based on existing models of PTSD or positive symptoms. No known studies have explored the potential maintaining factors of trauma-related voices in relation to ImRs. We aimed to uncover insights into the factors that maintain trauma-related voices and how ImRs may influence such factors by exploring voice hearers' explanations of voices and experiences of change throughout ImRs. DESIGN: Thematic analytical methodology was used due to the study's critical epistemological framework. METHODS: Semi-structured interviews explored relationships between trauma and voices, and experiences of change and stability throughout ImRs in a transdiagnostic sample (N = 10) who underwent 10-18 weekly ImRs sessions. Thematic analysis was used to develop themes. RESULTS: Two themes captured explanations of voices, which suggested voices may have counterproductive protective functions. Three themes captured psychological experiences during ImRs, which reflected concepts such as freedom to experience emotions, and experiences of justice, closure and grieving. Three themes described the outcomes of ImRs, reflecting concepts such as increased confidence, coping, perceived safety and voices becoming less powerful. CONCLUSIONS: Trauma-related voices may have underlying protective functions and ImRs may support emotional expression, adaptive trauma re-appraisals and improve self-worth and coping self-efficacy. These change processes may have clinical implications in ImRs and other treatments for trauma-affected voice hearers.

Does disorganised attachment lead to auditory hallucinations via dissociation? An experimental study with an analogue sample.

OBJECTIVES: Auditory hallucinations (such as hearing voices) are common in clinical and non-clinical populations. Many people who hear voices also report early adversity and have an insecure attachment style. Current cognitive models suggest that dissociation mediates an association between disorganised attachment and auditory hallucinations, but this has not been tested experimentally. DESIGN: We recruited a non-clinical analogue sample highly predisposed to auditory hallucinations and utilised an experimental design to examine the impact of disorganised attachment imagery on hallucinatory experiences, and whether dissociation mediates an expected association. METHODS: Participants completed self-report measures of state auditory hallucinations and dissociation before and after random allocation to secure or disorganised attachment conditions. RESULTS: Attachment imagery did not affect auditory hallucinations. Both secure and disorganised attachment conditions increased state dissociation. Secure attachment imagery reduced paranoia, but state dissociation did not mediate this effect. An exploratory analysis found that trait dissociation fully accounted for the association between trait-disorganised attachment and hallucinatory experience while controlling for paranoia. CONCLUSIONS: Secure attachment imagery reduces paranoia but not auditory hallucinations and the impact on paranoia is not mediated by dissociation. Secure attachment imagery may be useful in reducing fears and distress associated with voices, rather than the frequency or severity of hallucinations. Disorganised attachment may increase hallucinatory experiences for people vulnerable to dissociation. Trait dissociation should be assessed in clinical settings and addressed where indicated as a means of targeting vulnerability to distressing voices.

Pavlovian conditioning-induced hallucinations reduce MMN amplitudes for duration but not frequency deviants.

The mismatch negativity (MMN) is an evoked potential that indexes auditory regularity violations. Since the 90's, a reduced amplitude of this brain activity in patients with schizophrenia has been consistently reported. Recently, this alteration has been related to the presence of auditory hallucinations (AHs) rather than the schizophrenia diagnostic per se. However, making this attribution is rather problematic due to the high heterogeneity of symptoms in schizophrenia. In an attempt to isolate the AHs influence on the MMN amplitude from other cofounding variables, we artificially induced AHs in a non-clinical population by Pavlovian conditioning. Before and after conditioning, volunteers (N = 31) participated in an oddball paradigm that elicited an MMN. Two different types of deviants were presented: a frequency and a duration deviant, as the MMN alteration seems to be especially present in schizophrenia with the latter type of deviant. Hence, this pre-post design allowed us to compare whether experiencing conditioning-induced AHs exert any influence on MMN amplitudes. Our results show that duration-deviant related MMN reductions significantly correlate with the number of AHs experienced. Moreover, we found a significant correlation between AHs proneness (measured with the Launay-Slade Hallucination Extended Scale) and the number of AHs experienced during the paradigm. In sum, our study shows that AHs can be conditioned and exert similar effects on MMN modulation in healthy participants as has been reported for patients with schizophrenia. Thus, conditioning paradigms offer the possibility to study the association between hallucinations and MMN reductions without the confounding variables present in schizophrenia patients.

Brain mapping of auditory hallucinations and illusions induced by direct intracortical electrical stimulation.

BACKGROUND: The exact architecture of the human auditory cortex remains a subject of debate, with discrepancies between functional and microstructural studies. In a hierarchical framework for sensory perception, simple sound perception is expected to take place in the primary auditory cortex, while the processing of complex, or more integrated perceptions is proposed to rely on associative and higher-order cortices. OBJECTIVES: We hypothesize that auditory symptoms induced by direct electrical stimulation (DES) offer a window into the architecture of the brain networks involved in auditory hallucinations and illusions. The intracranial recordings of these evoked perceptions of varying levels of integration provide the evidence to discuss the theoretical model. METHODS: We analyzed SEEG recordings from 50 epileptic patients presenting auditory symptoms induced by DES. First, using the Juelich cytoarchitectonic parcellation, we quantified which regions induced auditory symptoms when stimulated (ROI approach). Then, for each evoked auditory symptom type (illusion or hallucination), we mapped the cortical networks showing concurrent high-frequency activity modulation (HFA approach). RESULTS: Although on average, illusions were found more laterally and hallucinations more posteromedially in the temporal lobe, both perceptions were elicited in all levels of the sensory hierarchy, with mixed responses found in the overlap. The spatial range was larger for illusions, both in the ROI and HFA approaches. The limbic system was specific to the hallucinations network, and the inferior parietal lobule was specific to the illusions network. DISCUSSION: Our results confirm a network-based organization underlying conscious sound perception, for both simple and complex components. While symptom localization is interesting from an epilepsy semiology perspective, the hallucination-specific modulation of the limbic system is particularly relevant to tinnitus and schizophrenia.

Alterations in the volume of thalamic nuclei in patients with schizophrenia and persistent auditory hallucinations.

The thalamus is a subcortical structure formed by different nuclei that relay information to the neocortex. Several reports have already described alterations of this structure in patients of schizophrenia that experience auditory hallucinations. However, to date no study has addressed whether the volumes of specific thalamic nuclei are altered in chronic patients experiencing persistent auditory hallucinations. We have processed structural MRI images using Freesurfer, and have segmented them into 25 nuclei using the probabilistic atlas developed by Iglesias and collaborators (Iglesias et al., 2018). To homogenize the sample, we have matched patients of schizophrenia, with and without persistent auditory hallucinations, with control subjects, considering sex, age and their estimated intracranial volume. This rendered a group number of 41 patients experiencing persistent auditory hallucinations, 35 patients without auditory hallucinations, and 55 healthy controls. In addition, we have also correlated the volume of the altered thalamic nuclei with the total score of the PSYRATS, a clinical scale used to evaluate the positive symptoms of this disorder. We have found alterations in the volume of 8 thalamic nuclei in both cohorts of patients with schizophrenia: The medial and lateral geniculate nuclei, the anterior, inferior, and lateral pulvinar nuclei, the lateral complex and the lateral and medial mediodorsal nuclei. We have also found some significant correlations between the volume of these nuclei in patients experiencing auditory hallucinations, and the total score of the PSYRATS scale. Altogether our results indicate that volumetric alterations of thalamic nuclei involved in audition may be related to persistent auditory hallucinations in chronic schizophrenia patients, whereas alterations in nuclei related to association cortices are evident in all patients. Future studies should explore whether the structural alterations are cause or consequence of these positive symptoms and whether they are already present in first episodes of psychosis.

Aberrant attentional modulation of the auditory steady state response (ASSR) is related to auditory hallucination severity in the first-episode schizophrenia-spectrum.

The 40-Hz auditory steady state response (ASSR) is reduced early in schizophrenia, with differences evident even at the first episode of schizophrenia-spectrum psychosis (FESz). Although robust, there is high variability in effect size across studies, possibly due to differences in experimental control of attention and heterogeneity of symptom profiles across studies, both of which may affect the ASSR. We investigated the relationships among ASSR deficits, attention-mediated sensory gain, and auditory hallucinations in 25 FESz (15 male; 23.3 ± 4.5 years) and 32 matched healthy comparison subjects (HC, 22 male; 24.7 ± 5.8 years). ASSR was measured to 40-Hz click trains at three intensities (75, 80, and 85 dB) while participants attended or ignored stimuli. ASSR evoked power and inter-trial phase coherence (ITPC) were measured using the Morlet wavelet transform. FESz did not show overall ASSR power reduction (p > 0.1), but power was significantly increased with attention in HC (p < 0.01), but not in FESz (p > 0.1). Likewise, FESz did not evince overall ASSR ITPC reduction (p > 0.1), and ITPC was significantly increased with attention in HC (p < 0.01), but not in FESz (p > 0.09). Attention-related change in ASSR correlated with auditory hallucination severity for power (r = -0.49, p < 0.05) and ITPC (r = -0.58, p < 0.01). FESz with auditory hallucinations may have pathologically increased basal excitability of auditory cortex and consequent reduced ability to further increase auditory cortex sensory gain with focused attention. These findings indicate hallucination-related pathophysiology early in schizophrenia and may guide novel intervention strategies aimed to modulate basal activity levels.

Limbic thalamus atrophy is associated with visual hallucinations in Lewy body disorders.

Recent models of hallucinations in Lewy body disorders implicate dysfunction in 'higher order' thalamic regions involved in perceptual integration and cognitive processing. However, the degree of pathology and degeneration in these regions has not been assessed. We sought to assess atrophy, neuronal size, and neuronal numbers in the Mediodorsal (MDn) and Anterior Principal (APn) nuclei of the thalamus across Lewy body disorders comparing between patients with and without hallucinations. Postmortem tissue was acquired from 24 patients with Lewy body disease and 10 age-matched controls and analyzed using standard stereological and quantitative neuropathological techniques. Atrophy in MDn was significantly greater in patients with well-formed visual hallucinations and did not correlate significantly with neuronal size or number. Atrophy in APn was seen across all Lewy body disorders but was not significantly associated with hallucinations. α-synuclein immunoreactivity was found to be low in both the APn and MDn across all groups. These results suggest that MDn atrophy may be a marker of hallucinations and plays a role in their pathophysiology.

The effects of voice content on stress reactivity: A simulation paradigm of auditory verbal hallucinations.

OBJECTIVES: Psychosis is associated with increased subjective and altered endocrine and autonomic nervous system stress-reactivity. Psychosis patients often experience auditory verbal hallucinations, with negative voice content being particularly associated with distress. The present study developed a voice-simulation paradigm and investigated the effect of simulated voices with neutral and negative content on psychophysiological stress-reactivity, and the effect of mindful voice-appraisals on stress-reactivity. METHOD: Eighty-four healthy participants completed the Montreal Imaging Stress Task with simultaneous presentation of one of three randomly allocated auditory stimuli conditions: negative voices, neutral voices or non-voice ambient sounds. Subjective stress-levels and mindful voice-appraisals were assessed using questionnaire measures, and cortisol and α-amylase levels were measured using saliva samples. RESULTS: ANOVA revealed a significant effect of condition on subjective stress-levels (p = .002), but not cortisol (p = .63) or α-amylase (p = .73). Post-hoc analyses showed that negative voices increased subjective stress-levels relative to neutral voices (p = .002) and ambient sounds (p = .01), which did not differ from each other (p = .41). Mindful voice-appraisals were associated with less distress across conditions (p = .003), although negative voices were also associated with less mindful appraisals (p < .001). CONCLUSIONS: Negative voice content, rather than voices or auditory stimuli per se, is linked to greater subjective but not physiological stress-reactivity. Mindful appraisals may partially moderate this effect. These findings highlight the importance of voice content for the impact of voice-hearing, and highlight the potential value of mindfulness training to treat voice distress in psychosis.

Peduncular hallucinosis after a thalamic stroke.

Peduncular hallucinosis is a rare form of hallucinations consisting of vivid and nonthreatening colourful visual hallucinations. It was first described by French neurologist Jean Lhermitte in 1922. It sometimes includes distorted images of animals and people. Peduncular hallucinosis has been described after vascular and infective lesions of the mesencephalon and thalamus.We present a case of peduncular hallucinosis after a right thalamic infarction. This is a case of a 75-year-old Caucasian man with a previous medical history of hypertension and hyperlipidaemia who presented as a transfer from an outside hospital with transient left facial palsy, upper and lower extremity weakness. His symptoms resolved on arrival. CTA head and neck revealed focal filling defect in the basilar artery and a right posterior cerebral artery (PCA) occlusion at its origin. MRI brain without contrast revealed a right thalamic infarct. The patient had vivid hallucinations including his wife sleeping on his hospital bed, seeing his favourite book on the table while he had left it at home, seeing his dogs and a TV show on his room television while it was off. He was easily redirectable, and the hallucinations resolved over 2 days without pharmacological intervention. In cases of thalamic, midbrain or peduncular infarctions, physicians should be cognizant of the possibility of peduncular hallucinosis and inquire about hallucinations. New onset hallucinations in a patient with no prior psychiatric history presenting with concerns for stroke should prompt physicians to strongly consider peduncular hallucinosis.

Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances.

Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.

Understanding the mental health burden of COVID-19 in the United Kingdom.

This article outlines the mental health burden of COVID-19 in the United Kingdom population, and presents preliminary evidence of less common psychiatric issues, such as paranoia and hallucinations, to which vulnerable groups in the U.K. population may be more vulnerable. It is argued that cognitive-behavioral therapy, with components of mindfulness, should be part of the therapeutic response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Thalamic pulvinar metabolism, sleep disturbances, and hallucinations in dementia with Lewy bodies: Positron emission tomography and actigraphy study.

OBJECTIVES: Although sleep disturbances are prevalent among patients with dementia with Lewy bodies (DLB), their neural substrates remain unclear. We aimed to clarify the neural substrates of sleep disturbances in patients with DLB. METHODS: We evaluated sleep disturbances, neuropsychiatric symptoms, and brain glucose metabolism in 22 patients with probable DLB using actigraphy, the Neuropsychiatric Inventory (NPI), and 18 F-fluorodeoxyglucose (FDG) positron emission tomography, respectively. Total sleep time (TST) and average activity count per minute (AAC) during sleep were calculated for seven consecutive days via actigraphy. We investigated associations between FDG uptake and the actigraphy parameters using Statistical Parametric Mapping version 12b. Spearman's rank correlation coefficients were used to investigate associations among TST, AAC, and clinical symptoms. The level of statistical significance was set at P < .05. P values were adjusted using the Benjamini-Hochberg method for multiple comparisons. This study was registered with ClinicalTrials.gov (NCT00776347). RESULTS: TST exhibited a significant positive association with FDG uptake in the bilateral orbitofrontal cortex and left thalamus, while AAC exhibited a significant negative association with FDG uptake in the left thalamus and the left parieto-occipital region. FDG uptake in the left pulvinar was associated with both TST and AAC. In addition, TST exhibited a significant negative association with the NPI hallucinations score (r = -0.66, P = .001), while AAC exhibited significant positive associations with the NPI delusions (r = 0.70, P < .001) and hallucinations (r = 0.63, P = .002) scores. CONCLUSIONS: TST and bodily activity during sleep are associated with dysfunction of the left pulvinar and the severity of hallucinations in patients with DLB.

Paediatric migraine with visual hallucination auras appearing in the form of a human body.

The most common type of migraine aura is multifaceted visual aura, such as scintillating scotoma or geometrical patterns, visual hallucinations in which a physical body is extremely rare. We report a paediatric case of migraine in which visual hallucinations appeared as auras in the form of a human body. The patient was an 11-year-old girl suffering from migraine with curious visual aura. The auras were atypical visual hallucinations that were sometimes accompanied by auditory hallucinations. Approximately 5-20 min before the headache, the patient would see a middle-aged man wearing sunglasses in her field of vision. Acetaminophen (10 mg/kg) and Japanese herbal medicine administered when necessary effectively treated the headaches. Finally, the patient was no longer complaining of her hallucination auras. Although the pathophysiology of migraines accompanied by auras is unclear, it appears that cerebral blood flow and cortical spreading depression are involved in auras.

Visual hallucinations, thalamocortical physiology and Lewy body disease: A review.

One of the core diagnostic criteria for Dementia with Lewy Bodies (DLB) is the presence of visual hallucinations. The presence of hallucinations, along with fluctuations in the level of arousal and sleep disturbance, point to potential pathological mechanisms at the level of the thalamus. However, the potential role of thalamic dysfunction in DLB, particularly as it relates to the presence of formed visual hallucinations is not known. Here, we review the literature on the pathophysiology of DLB with respect to modern theories of thalamocortical function and attempt to derive an understanding of how such hallucinations arise. Based on the available literature, we propose that combined thalamic-thalamic reticular nucleus and thalamocortical pathology may explain the phenomenology of visual hallucinations in DLB. In particular, diminished α7 cholinergic activity in the thalamic reticular nucleus may critically disinhibit thalamocortical activity. Further, concentrated pathological changes within the posterior regions of the thalamus may explain the predilection for the hallucinations to be visual in nature.

Neurofeedback of core language network nodes modulates connectivity with the default-mode network: A double-blind fMRI neurofeedback study on auditory verbal hallucinations.

BACKGROUND: The experience of auditory verbal hallucinations in schizophrenia is associated with changes in brain network function. In particular, studies indicate altered functional coupling between nodes of the language and default mode networks. Neurofeedback based on real-time functional magnetic resonance imaging (rtfMRI) can be used to modulate such aberrant network connectivity. METHODS: We investigated resting-state connectivity changes after neurofeedback (NF) in 21 patients with schizophrenia and 35 healthy individuals. All participants underwent two days of neurofeedback training of important nodes of the left-hemispheric language network including the inferior frontal gyrus (IFG) and posterior superior temporal gyrus (pSTG). In a double-blind randomized cross-over design, participants learned to down- and up-regulate their brain activation in the designated target regions based on NF. Prior to and after each training day, a resting state measurement took place. RESULTS: Coupling between nodes of the language and the default mode network (DMN) selectively increased after down-as compared to up-regulation NF. Network analyses revealed more pronounced increases in functional connectivity between nodes of the language network and the DMN in patients compared to healthy individuals. In particular, down-regulation NF led to increased coupling between nodes of the language network and bilateral inferior parietal lobe (IPL) as well as posterior cingulate cortex (PCC)/precuneus in patients. Up-regulation strengthened connectivity with the medial prefrontal cortex (mPFC). Improved well-being four weeks after the training predicted increased functional coupling between the left IFG and left IPL. CONCLUSION: Modulatory effects emerged as increased internetwork communication, indicating that down-regulation NF selectively enhances coupling between language and DM network nodes in patients with AVH. RtfMRI NF may thus be used to modulate brain network function that is relevant to the phenomenology of AVH. Specific effects of self-regulation on symptom improvement have to be explored in therapeutic interventions.