Imagery-Focused Therapy for Visual Hallucinations: A Case Series.

INTRODUCTION: Visual hallucinations (VH) are more common than previously thought and are linked to higher levels of distress and disability in people with a psychotic illness. Despite this, scant attention has been given to VHs in the clinical literature, and the few therapy case series of cognitive behavioural therapy (CBT) published to date have not demonstrated reliable change. In other areas of clinical research, problematic mental imagery has been found to be more strongly related to negative affect in psychological disorders than negative linguistic thinking, and imagery focused techniques have commonly been found to improve the outcomes in CBT trials. Given VHs have many similarities with visual mental imagery and many of the distressing beliefs associated with VHs targeted in CBT are maintained by accompanying mental imagery (i.e., imaging a hallucinated figure attacking them), it seems plausible that an imagery-focused approach to treating VHs may be most effective. METHODS: The current study is a multiple baseline case series (N = 11) of a 10-session imagery-focused therapy for VH in a transdiagnostic sample. RESULTS: The study had good attendance and feedback, no adverse events and only one [seemly unrelated] drop-out, suggesting good feasibility, safety and acceptability. The majority of clients reported reduction on both full-scale measures (administered at 3 baselines, midtherapy, posttherapy and 3-month follow-up) and weekly measures of VH severity and distress, ranging from medium to large effect sizes. CONCLUSIONS: The case series suggests that an imagery-focused approach to treating VHs may be beneficial, with a recommendation for more rigorous clinical trials to follow.

Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): Findings from an exploratory randomised controlled trial.

Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n = 40) or TAU alone (n = 42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment.

Immersive virtual reality in the treatment of auditory hallucinations: A PRISMA scoping review.

BACKGROUND: A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging. OBJECTIVE: The aim of this scoping review is to provide an overview of clinical trials utilizing VR in the treatment of AH and to document knowledge gaps in the literature. METHODS: PubMed, Cochrane Library, and Embase were searched for studies reporting on the use of VR to target AH. RESULTS: 16 papers were included in this PRISMA scoping review (ScR). In most studies VR therapy (VRT) was employed to ameliorate treatment resistant AVH in schizophrenia spectrum disorders. Only two studies included patients with a diagnosis of affective disorders. The VRT was carried out with the use of an avatar to represent the patient's most dominant voice. DISCUSSION: The research field employing VR to treat AH is promising but still in its infancy. Results from larger randomized clinical trials are needed to establish substantial evidence of therapy effectiveness. Additionally, the knowledge base would benefit from more profound qualitative data exploring views of patients and therapists.

Functional and structural effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations in schizophrenia: A systematic review.

BACKGROUND: Auditory verbal hallucinations (AVH) are a disabling symptom for people with schizophrenia (SCZ), and do not always respond to antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for medication-refractory AVH, though the underlying neural mechanisms by which rTMS produces these effects remain unclear. This systematic review evaluated the structural and functional impact of rTMS for AVH in SCZ, and its association with clinical outcomes. METHODS: A systematic search was conducted in Medline, PsychINFO, and PubMed using terms for four key concepts: AVH, SCZ, rTMS, neuroimaging. Using PRISMA guidelines, 18 studies were identified that collected neuroimaging data of an rTMS intervention for AVH in SCZ. Risk of bias assessments was conducted. RESULTS: Low frequency (<5 Hz) rTMS targeting left hemispheric language processing regions may normalize brain abnormalities in AVH patients at structural, functional, electrophysiological, and topological levels, with concurrent symptom improvement. Amelioration of aberrant neural activity in frontotemporal networks associated with speech and auditory processing was commonly observed, as well as in cerebellar and emotion regulation regions. Neuroimaging analyses identified neural substrates with direct correlations to post-rTMS AVH severity, propounding their use as therapeutic targets. DISCUSSION: Combined rTMS-neuroimaging highlights the multidimensional alterations of rTMS on brain activity and structure in treatment-resistant AVH, which may be used to develop more efficacious therapies. Larger randomized, sham-controlled studies are needed. Future studies should explore alternate stimulation targets, investigate the neural effects of high-frequency rTMS and evaluate long-term neuroimaging outcomes.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

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.

Intersections of phenomenology, voice beliefs and distress in bipolar disorder: a comparison with schizophrenia.

BACKGROUND: Auditory verbal hallucinations (AVH), or voice-hearing, can be a prominent symptom during fluctuating mood states in bipolar disorder (BD). AIMS: The current study aimed to: (i) compare AVH-related distress in BD relative to schizophrenia (SCZ), (ii) examine correlations between phenomenology and voice beliefs across each group, and (iii) explore how voice beliefs may uniquely contribute to distress in BD and SCZ. METHOD: Participants were recruited from two international sites in Australia (BD=31; SCZ=50) and the UK (BD=17). Basic demographic-clinical information was collected, and mood symptoms were assessed. To document AVH characteristics, a 4-factor model of the Psychotic Symptoms Rating Scale and the Beliefs about Voices Questionnaire-Revised were used. Statistical analyses consisted of group-wise comparisons, Pearson's correlations and multiple hierarchical regressions. RESULTS: It was found that AVH-related distress was not significantly higher in BD than SCZ, but those with BD made significantly more internal attributions for their voices. In the BD group, AVH-related distress was significantly positively correlated with malevolence, omnipotence and resistance, However, only resistance, alongside mania and depressive symptoms, significantly contributed to AVH-related distress in BD. DISCUSSION: Our findings have several clinical implications, including identification of voice resistance as a potential therapeutic target to prioritise in BD. Factoring in the influence of mood symptoms on AVH-related distress as well as adopting more acceptance-oriented therapies may also be of benefit.

A pilot trial examining the effects of veteran voices and visions, an adaptation of hearing voices groups for a large public health system in the United States.

BACKGROUND: The Hearing Voices Approach, a community-based peer-led support group model, is generating interest as a novel way to engage with psychosis. Hearing Voices (HV) groups are run by peers, 'experts-by-experience', and emphasize group ownership and community-building rather than adherence to a therapist-led, predetermined structure. Diverse beliefs about experiences are respected and viewed as potentially meaningful. Groups work within each individual's explanatory framework to reframe understandings. AIMS: This paper describes the effects of participation in Veteran Voices and Visions (VVV) groups, an adaptation of the HV approach, co-led by clinicians and Veteran peer support specialists, adapted for Veterans who have experienced psychosis and receive care at the VA, a large public health system in the United States. METHOD: This mixed methods pilot study has a convergent parallel design, integrating quantitative and qualitative data from participants in pre-intervention and post-intervention assessments. RESULTS: Over 16 weeks, quantitative analysis showed a statistically significant reduction in distress, due to auditory hallucinations, as measured by the Psychotic Symptom Rating Scales (PSYRATS). The Beliefs about Voices Questionnaire- Revised (BAVQ-R) results showed a reduction in malevolence and omnipotence and an increase in benevolence related to auditory hallucinations, but no change in resistance. Engagement showed a trend-level reduction. Qualitative data from midpoint (Week 8) and endpoint (Week 16) interviews revealed several perceived benefits from groups: 1) normalization and camaraderie, 2) increased hope and confidence, 3) self-understanding and reframing of experiences, and 4) building relationships outside of groups. Overall, VVV groups reduced distress due to voices, negative beliefs about voices, and perceived power of voices. CONCLUSIONS: Study findings contribute to a growing body of literature indicating HV groups support those who have experienced psychosis by reducing social isolation and fostering community, which may facilitate social integration. Overall, our findings highlight the potential benefits of adapting HV groups to health systems.

Rich-club reorganization of white matter structural network in schizophrenia patients with auditory verbal hallucinations following 1 Hz rTMS treatment.

The human brain comprises a large-scale structural network of regions and interregional pathways, including a selectively defined set of highly central and interconnected hub regions, often referred to as the "rich club", which may play a pivotal role in the integrative processes of the brain. A quintessential symptom of schizophrenia, auditory verbal hallucinations (AVH) have shown a decrease in severity following low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the underlying mechanism of rTMS in treating AVH remains elusive. This study investigated the effect of low-frequency rTMS on the rich-club organization within the brain in patients diagnosed with schizophrenia who experience AVH using diffusion tensor imaging data. Through by constructing structural connectivity networks, we identified several critical rich hub nodes, which constituted a rich-club subnetwork, predominantly located in the prefrontal cortices. Notably, our findings revealed enhanced connection strength and density within the rich-club subnetwork following rTMS treatment. Furthermore, we found that the decreased connectivity within the subnetwork components, including the rich-club subnetwork, was notably enhanced in patients following rTMS treatment. In particular, the increased connectivity strength of the right median superior frontal gyrus, which functions as a critical local bridge, with the right postcentral gyrus exhibited a significant correlation with improvements in both positive symptoms and AVH. These findings provide valuable insights into the role of rTMS in inducing reorganizational changes within the rich-club structural network in schizophrenia and shed light on potential mechanisms through which rTMS may alleviate AVH.

[Pilot study of Experience Focused Counselling by nurses with people who hear voices: Evaluation of the implementation of the study protocol]. / Pilotstudie zu Erfahrungsfokussierter Beratung durch Pflegende bei Menschen, die Stimmen hören.

Pilot study of Experience Focused Counselling by nurses with people who hear voices: Evaluation of the implementation of the study protocol Abstract: Background: Hearing voices and the treatment and support of people who hear voices and are distressed by the experience are defined differently in psychiatry. In contrast to the medical approach to define and treat voices as symptoms of a disease, the EFC counselling approach developed with voice-hearers focuses on non-pathologizing acceptance and a constructive relationship to voices. Mental health nurses with their focus on everyday life are predestined for the dissemination and application of alternative therapeutic approaches in practice. Aim: The aim was to evaluate the study protocol as part of a pilot study regarding its suitability for a larger trial. Method: The multi centre pilot study had a single-blind randomised controlled design. The intervention consisted of EFC counselling by nurses with people who hear voices. The control group received Treatment As Usual (TAU). The suitability of the study design was evaluated in terms of recruitment, burden on study participants, suitability of assessment tools, the application of EFC counselling and the use of study nurses. Results: As planned 21 participants could be included in the study within fifteen months across the two study sites. Overall, the participants rated the study as not very burdensome and the intervention as helpful. The application of EFC by the nurses as well as the use of study nurses was assessed as good and suitable respectively. Discussion: The evaluation of the study protocol shows that with minor adjustments it is suitable for conducting a larger study.

The Experience of Hearing Voices: Challenges and Coping Mechanisms.

Auditory hallucinations or hearing voices are often associated with schizophrenia and other psychotic disorders. However, several voice-hearers do not have any mental health issues or diagnoses. The study presented in this paper aimed to explore how voice-hearers understand and react to their concerns by reflecting on and exploring their experiences and interpretations of these experiences. The participants were nine individuals - three females, four males and two others, all experiencing auditory hallucinations for at least five years, residing either at their home or at one of the Hostels run by Richmond Foundation (Malta). A qualitative approach following the principles of Interpretative Phenomenological Analysis was used. In-depth interviews were conducted to explore how the participants perceive their voices, what coping strategies are used, and how their experiences affect their lives. Four super-ordinate themes related to the participants' perceptions and their interpretation of the experience of hearing voices were identified: 'A tough experience', 'Methods used to cope with voices', 'Factors linked to recovery' and 'Relationships'. Furthermore, the study elicited the voice-hearers' recommendations (both for other voice-hearers and mental health professionals).

Pulvinar quantitative susceptibility mapping predicts visual hallucinations post-deep brain stimulation in Parkinson's disease.

PURPOSE: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS. METHODS: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively. RESULTS: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037). CONCLUSIONS: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment.

Alterations in brain connectivity patterns in schizophrenia patients with auditory verbal hallucinations during low frequency repetitive transcranial magnetic stimulation.

OBJECTIVE: Auditory verbal hallucinations (AVH) are a characteristic symptom of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to alleviate the severity of AVH, its exact neurophysiological mechanisms remain unclear. This study aimed to elucidate the alterations in brain connectivity patterns in schizophrenia patients with AVH after low frequency rTMS. Furthermore, the relationship between these alterations and clinical outcomes was examined, thereby identifying potential biomarkers for rTMS treatment efficacy. METHODS: A total of 30 schizophrenia patients with AVH and 33 healthy controls were recruited. The patients received 1 Hz rTMS applied to the left temporoparietal junction region over 15 days. Resting-state functional magnetic resonance imaging scans were conducted for all participants. Subsequently, degree centrality (DC) and seed-based functional connectivity (FC) analyses were employed to identify specific alterations in brain connectivity patterns after rTMS treatment. RESULTS: At baseline, patients exhibited divergent DC patterns in the frontal, occipital, and limbic lobes compared to healthy controls. In addition, prior to treatment, patients demonstrated altered FC from the superior frontal gyrus seeds that linked to the frontal, temporal, and somatosensory regions. Following rTMS treatment, these abnormalities were notably reversed, correlating with improved clinical outcomes. CONCLUSIONS: These findings demonstrate that schizophrenia patients with AVH exhibited atypical interactions within the frontal and temporal lobes. These alterations might be crucial biomarkers for predicting the efficacy of low frequency rTMS.

When therapists talk to voices: Perspectives from service-users who experience auditory hallucinations.

PURPOSE: The purpose of the study was to investigate service-users' experiences of a therapist engaging with their voices (auditory hallucinations) using psychological formulation and direct dialogue. METHOD: A nested qualitative study was conducted within a randomised controlled trial of a novel intervention for supporting voice hearers with a diagnosis of psychosis (Talking With Voices: TwV). Of 24 participants allocated to therapy, 13 (54%) consented to a semi-structured, in-depth interview which was audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS: Participants described their experiences of using the intervention to improve the relationship between themselves and their voice(s). The findings are organised within three themes and associated subthemes: (1) A desire for suitable help (Motivation to reduce voice-related distress, Limitation of other treatment options); (2) Engaging with voices (Challenges, Support and safety, Exploration and revelation); and (3) Contemplating the future (The aftermath of adversity, Living well with voices, Resources for moving forward). CONCLUSION: Despite the emotional challenges of the work, many participants experienced tangible gains in the ways they related to their voices post-intervention. For those who responded well, the development of safety strategies, including a strong therapeutic alliance, could facilitate a basis for developing new insights about the origin/nature of the voices which could then be applied in constructive ways. Further research is needed to understand which client characteristics indicate suitability for TwV as opposed to relational therapies that require less direct engagement with voices and/or the psychosocial conflicts with which they may be associated.

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.

Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial.

INTRODUCTION: Individuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment is a brief symptom targeted intervention that draws on psychological explanations to help account for unusual experiences. Practitioners use formulation and behavioural experiments to support individuals to make sense of their experiences and enhance coping strategies. The primary objective of this feasibility trial is to resolve key uncertainties before a definitive trial and inform parameters of a future fully powered trial. METHODS AND ANALYSIS: 88 participants aged 14-35 accepted into ARMS services, experiencing hallucinations/unusual sensory experiences which are considered by the patient to be a key target problem will be recruited from UK National Health Service (NHS) sites and randomised using 1:1 allocation (stratified by site, gender, and age) to either 6-8 sessions of MUSE or time-matched treatment as usual. Participants and therapists will be unblinded, research assessors are blinded. Blinded assessment will occur at baseline, 12 weeks and 20 weeks postrandomisation. Data will be reported in line with Consolidated Standards of Reporting Trials. Primary trial outcomes are feasibility outcomes, primary participant outcomes are functioning and hallucinations. Additional analysis will investigate potential psychological mechanisms and secondary mental well-being outcomes. Trial progression criteria follows signal of efficacy and uses an analytical framework with a traffic-light system to determine viability of a future trial. Subsequent analysis of the NHS England Mental Health Services Data Set 3 years postrandomisation will assess long-term transition to psychosis. ETHICS AND DISSEMINATION: This trial has received Research Ethics Committee approval (Newcastle North Tyneside 1 REC; 23/NE/0032). Participants provide written informed consent; young people provide assent with parental consent. Dissemination will be to ARMS Services, participants, public and patient forums, peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ISRCTN58558617.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brain perfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.