Neuro-VR: 幻聴に対するニューロフィードバックによる仮想現実ベースの治療の強化 (Neuro-VR)

Participants in the experimental group undergo 8 sessions of a manualized virtual reality-based intervention added real-time EEG neurofeedback aiming to enhance the control and sense of power in relation to the dominant hallucinated voice. Together with the therapist, the participants create a digital representation (avatar) in virtual reality corresponding to the visual perception and sound of the voice. During therapy, the participants will be encouraged to engage in a dialogue with the avatar. While immersed in virtual reality, EEG recordings will be conducted by electrodes connected to a cap on the participants' head. Processed EEG-data will provide real-time information on the participants' brain activity associated with the emotional distress when confronted with the avatar and will be visible both to the participant and therapist. The feedback will be used to continuously adjust the intervention to the brain activity and aims to help the participant practice emotion regulation.

Virtual Reality-based intervention augmented with real-time EEG-based neurofeedback targeting auditory hallucinations in schizophrenia

Participants in the control group will be offered 8 sessions of a manualized virtual reality - based therapy that follows the same principles as described in the experimental arm. Together with the therapist, the participants create a digital representation (avatar) in virtual reality that corresponds to their visual perception of and sounds like their hallucinated voice. Thoughout the therapy sessions, the participants will be encouraged to engage in a dialogue with the 'avatar', voiced by the therapist who will alternate between talking as the 'avatar' and as a supportive therapist. The therapy aims at enhancing the participants' control and feeling of power in relation to the dominant hallucinated voice. Furthermore, the therapy focuses on regulating the emotional distress associated with the hallucinated voice.

Virtual Reality-based intervention targeting auditory hallucinations in schizophrenia

Percentage of target sample (30 participants) recruited after 12 months from study start.

Percentage of included participants in the experimental group who retent to treatment at cessation of therapy (8 sessions).

Percentage of participants in the experimental group reporting a satisfaction rating of more than 7 on a Likert scale ranging from 1-10 with higher scoring indicating a higher level of satisfaction with therapy.

SAPS is an interviewer-administered instrument with 34 items measuring positive symptoms in schizophrenia. Each item is rated on a 6-point scale ranging from None (0) to Severe (5) with higher scoring reflecting greater severity of positive symptoms.

PSYRATS-AH is an interviewer-administered instrument with 11 items assessing characteristics of hallucinations: frequency; duration; location; loudness; beliefs about origin of voices; amount of negative content of voices; degree of negative content; amount of distress; intensity of distress; disruption and control.

Each item is rated on a 5-point scale (0-4) with higher scores reflecting greater severity of auditory hallucinations.

Additionally, an optional item measuring Number of Voices will be included.

The VAAS is a self-report scale assessing level of acceptance of and action in relation to the hallucinated voices rated on a 5-point Likert scale ranging from 'Strongly Disagree' (1) to 'Strongly Agree' (5) with higher scores reflecting higher levels of acceptance and action in relation to the hallucinated voices.

The BAVQ-R is a self-report questionnaire assessing beliefs about hallucinated voices. Each item is rated on a 4-point scale ranging from Disagree (0), Unsure (1), Slightly agree (2), Strongly agree (3) with higher scores indicating greater endorsement of a belief.

The VPDS is a self-report questionnaire with seven items rated on a 5-point scale (1-5) with a total score ranging from 7-35. Higher scores indicate that the voice is perceived to have greater power compared to the respondent.

At therapy sessions 1 and 8, the participants will be asked to complete the questionnaire focusing on the hallucinated voice they choose to focus on during therapy.

The Assertive Responding to Voices (Approve - Voices) questionnaire comprises 15 items assessing different ways to respond to the hallucinated voices.

Scores range from 0-10 with higher scores indicating higher degree of the specific responding to voices.

At therapy sessions 1 and 8, the participants will be asked to complete the questionnaire focusing on the hallucinated voice they choose to focus on during therapy.

The PSP is an interviewer administered instrument assessing different domains of social and daily functioning: job/education, social relations, personal hygiene and aggressive behaviour.

A total score ranges from 1-100 with higher scores indicating a higher degree of functioning.

The SFS is a self-report instrument assessing social functioning among individuals with schizophrenia.

The instrument comprises seven domains: Social engagement/withdrawal, Interpersonal behaviour, Prosocial activities, Recreation, Independence-competence, Independence-performance and Employment/occupation.

The minimum raw score is 0 and maximum raw score is 223 with higher scoring indicating a higher level of functioning.

The BNSS is a an interviewer-administered instrument comprising 13 items and five domains of negative symptoms: anhedonia, asociality, avolition, blunted effect and alogia.

Each item is rated on a 7-point scale (0-6) with higher scores reflecting a higher level of negative symptoms.

The SNS is a self-report questionnaire with 20 items rated on 3-point scale ranging from Strongly agree (2) to Strongly disagree (0). A total score ranges from 0 to 40 with higher scoring reflecting a higher degree of self-evaluated negative symptoms.

The ERQ is a self-report questionnaire with 10 items that measure the extent to which the respondent regulates and manages emotions using two different strategies: cognitive reappraisal and expressive suppression.

Each item is rated on a 7-point scale ranging from Completely disagree (1) to Completely agree (7).

The two subscales are scored separately with higher scores reflecting greater use of the specific strategy.

The DERS-16 is a self-report questionnaire with 16 items assessing different dimensions of emotion regulation difficulties: Nonacceptance of negative emotions, Inability to engage in goal-directed behaviors when distressed, Difficulties controlling impulsive behaviors when distressed, Limited access to emotion regulation strategies perceived as effective and Lack of emotional clarity.

Each item is rated on a 5-point Likert-scale ranging from Almost never (1) to Almost always (5). A total score is calculated by summing the scores of the different subscales ranging from 16 to 80 with higher scores reflecting greater levels of emotion dysregulation.

The BCSS is a self-report questionnaire with 24 items assessing four dimensions of schemata concerning self and others: Negative-self, Positive-self, Negative-others and Positive-others.

Each item is rated on a 5-point scale ranging from No (0) to Believe it totally (4) with higher scores indicating greater endorsement of a schema.

The CSQ is a self-report questionnaire with 8 items measuring client satisfaction with the intervention.

Each item is scored on a 4-point scale ranging from 1-4 with higher scores reflecting greater satisfaction with intervention.

The SSQ is a self-report questionnaire with 16 items measuring different symptoms of simulator sickness. Each item is rated on a 4-point scale ranging from None (0) to Severe (3) with higher scores indicating a higher level of symptoms.

The CDSS is an interviewer-administered instrument comprising 9 items assessing level of depression among individuals with schizophrenia. Each item is rated on a 4-point scale ranging from Absent (0) to Severe (3) with higher scores indicating a higher level of depressive symptoms.

The SIDAS is a self-report questionnaire with 5 items measuring different aspects of suicidal thoughts: frequency, controllability, closeness to attempt, level of distress associated with the thoughts and impact on daily functioning.

Each item is rated on a 11-point scale ranging from 0-10 with higher scores reflecting greater severity of suicidal thoughts.

The CTQ is a retrospective, self-report questionnaire with 28 items measuring traumatic experiences in childhood.

Each item is rated on a 5-point Likert scale ranging from Never (1) to Very often (5) with higher scores reflecting greater severity of childhood trauma.

The WHO-5 is a self-report questionnaire with 5 items measuring subjective psychological well-being. Each item is scored on a 6-point scale ranging At no time (0) to All of the time (5).

A total raw score is ranging from 0 to 25. To calculate the final score, the total raw score is multiplied by 4 with higher scores reflecting higher levels of well-being.

The PSQI is a self-report questionnaire measuring sleep quality and disturbances over a 1-month time.

The questionnaire consists of a combination of Likert- type and open-ended questions with higher scores indicating higher level of sleep disturbances.

The GSE is a self-report questionnaire with 10 items meausering percevied self-efficacy. Each item is rated on a 4-point scale ranging from Not at all true (1) to Exactly true (4) with higher scores reflecting greater self-efficacy.

Total score ranges from 10 to 40.

The BIS is a self-report questionnaire with 8 items measuring insight in mental illness. Each item is rated on a 3-point scale ranging from Agree, Disagree to Unsure.

A total score is calculated by summing the scores of three subscales (Awareness of symptoms, Awareness of illness and Need for treatment) and ranges from 0-12 with higher scores reflecting greater insight into illness.

The RTQ is a self-report questionnaire with 6 items measuring positive attitude and preparedness to enter therapy.

Each item is rated on a 5-point Likert scale ranging from Strongly disagree (0) to Strongly agree (4).

Items 2, 3 and 6 are reversed scored. A higher score reflects greater readiness for therapy.

P50 suppression is a measure of sensory gating that can be assessed by measuring electroencephalographic (EEG) responses to repeated pairs of auditory clicks The participants will be instructed to count auditory clicks, either in pairs or individually, while keeping the eyes closed.

The paradigm will last for a total of 21 minutes, divided into 3 intervals of 7 minutes each.

The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli. The participants will watch a movie on a screen while hearing some pure tones. The participants will be instructed to try to ignore the tones and not react on them, sitting as still as possible.

This paradigm lasts 12 minutes.

ASSRs are evoked brain responses to repeated auditory stimulus. A sequence of tones is repeatedly presented to the participants. The participants are instructed to keep their gaze fixed on a cross displayed on a screen in front of them while they sit as still as possible.

This paradigm lasts 6 minutes.

A Selective Attention (SA) paradigm will measure the ability to focus on relevant information, while filtering out distracting information.

The participants will be presented to standard auditory stimuli, followed by a deviant stimulus with a higher frequency across both ears. The participants will be instructed to press a button if they hear a deviant stimulus on a specific ear.

EEG recordings at resting state will measure spontaneous neural activity. The participants will be instructed to sit as still as possible while keeping their eyes open and fixed on a cross displayed on a screen in front of them. The participants will be instructed to not think of anything in specific.

This paradigm will last 5 minutes.

Qualitative semi-structured interviews with participants and therapists will be conducted to investigate their experiences with the experimental intervention.