Auditory Hallucination
Conditions
Brief summary
Auditory verbal hallucinations (AVH) are prevalent among patients with psychiatric disorders. Not only being highly stressful and functionally impairing, AVH often persist despite treatment. Recent attempts to treat AVH with add-on repetitive transcranial magnetic stimulation (rTMS) when targeting the temporoparietal junction (TPJ), a language node in the brain, has gained limited success. The aim of this investigation is to reduce AVH with rTMS using continous theta-burst stimulation over a novel target, the supplementary motor area (SMA), in participants with frequent AVH, while also assessing potential neurophysiological mechanisms underlying the symptom.
Interventions
DEVICEcontinuous theta burst stimulation over the SMA
Each cTBS session consists of bursts of three pulses delivered with a rate of 50 Hz, with bursts repeated at a rate of 5 Hz for a total duration of 40 seconds, summing up to 600 pulses, 100% of motor threshold (MT) and applied over bilateral SMA. The target is located in the anterior-posterior direction over the transition between pre-SMA and SMA proper, (cortical point where a vertical line will pass through the anterior commissure). The center of a figure-of-eight coil will be placed over the target, guided with neuronavigation equipment that utilizes the anatomical brain image from the pre-cTBS scanning session.
DEVICEsham continuous theta burst stimulation over the SMA
The same stimulation parameters but a concealed sham coil will be used with only superficial magnetic stimulation to mimic the sensation of the active stimulation
Sponsors
Uppsala University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Identical sham coil, masked by an independent person.
Intervention model description
First phase is a cross-over with two randomized blinded sessions with either verum cTBS or sham with wash-out, for each participant, and a second open feasibility treatment phase with 5 sessions/day over four days for participants with distressing auditory verbal hallucinations
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for the AVH group: * Reported AVH with a minimum frequency of at least daily occurrence, with onset more than one month ago * Stable psychopharmacological treatment past month Inclusion criteria for the non-AVH control group * Reporting no occurrences of AVH for the past year * Stable psychopharmacological treatment past month Inclusion criteria for the healthy control group * No life-time occurrence of AVH * No history of psychiatric disorders as assessed with a Mini-International Neuropsychiatric Interview (M.I.N.I.)
Exclusion criteria
* Ferromagnetic or electromagnetic implants that may pose a risk during magnetic resonance imaging (MRI) and/or cTBS * A history of epilepsy * Pregnancy * Current substance use disorder or a history of alcohol use disorder as assessed with Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), urine samples with test for illicit drugs and Phosphatidylethanol (PEth) * Daily benzodiazepine use * Factors that make the participant unlikely to be able to complete the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change on The Psychotic Symptom Rating Scales (PSYRATS) | 1 day after completion of open treatment phase | Auditory Verbal Hallucination symptom interview, total score |
| Amplitude on EEG in speech-listen task | 5-30 minutes after intervention | Neurophysiological outcome of the blinded cross-over phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Finger tapping test | 5-30 minutes after intervention | Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance |
| Double step saccade-task | 20-60 minutes after intervention | Performance (Zimmermann et al Sci Rep, 2018). |
| Resting state functional magnetic resonance imaging (rsfMRI) | 1 day after completion of open treatment phase | Resting state SMA connectivity change as measured with fMRI |
| Magnetic resonance spectroscopy (MRS) over the SMA quantifying glutamate and gamma-aminobutyric acid (GABA) and other metabolites | 1 day after completion of open treatment phase | Prefrontal GABA and Glutamate concentration change as measured with a MEGA-PRESS magnetic resonance spectroscopy sequence following intervention. |
| Brief Psychiatric Rating Scale (BPRS) | 1 day after completion of open treatment phase | Total score |
| App recorded ratings of auditory verbal hallucinations (AVH) | From first day of open treatment phase, and through one week after completion of treatment | 5 times a day randomized time points for app ratings of AVH |
Countries
Sweden
Outcome results
None listed