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Slow recruitment
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open label active cTBS | Experimental | Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations |
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| active cTBS | Experimental | One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase |
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| Sham cTBS | Sham Comparator | One test session with 40s sham cTBS, 100% MT, over the SMA in the initial double blind cross-over phase with a special sham coil that diverts the magnetic field to be only superficial |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| continuous theta burst stimulation over the SMA | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Amplitude on EEG in speech-listen task | Neurophysiological outcome of the blinded cross-over phase | 5-30 minutes after intervention |
| Change on The Psychotic Symptom Rating Scales (PSYRATS) | Auditory Verbal Hallucination symptom interview, total score | 1 day after completion of open treatment phase |
| Measure | Description | Time Frame |
|---|---|---|
| Finger tapping test | Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance | 5-30 minutes after intervention |
| Double step saccade-task |
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Inclusion Criteria:
Inclusion criteria for the AVH group:
Inclusion criteria for the non-AVH control group
Inclusion criteria for the healthy control group
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Boden, MD | Uppsala University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials | Uppsala | 751 85 | Sweden |
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| ID | Term |
|---|---|
| D006212 | Hallucinations |
| ID | Term |
|---|---|
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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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
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Identical sham coil, masked by an independent person.
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| sham continuous theta burst stimulation over the SMA | Device | 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 |
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Performance (Zimmermann et al Sci Rep, 2018).
| 20-60 minutes after intervention |
| Resting state functional magnetic resonance imaging (rsfMRI) | Resting state SMA connectivity change as measured with fMRI | 1 day after completion of open treatment phase |
| Magnetic resonance spectroscopy (MRS) over the SMA quantifying glutamate and gamma-aminobutyric acid (GABA) and other metabolites | Prefrontal GABA and Glutamate concentration change as measured with a MEGA-PRESS magnetic resonance spectroscopy sequence following intervention. | 1 day after completion of open treatment phase |
| Brief Psychiatric Rating Scale (BPRS) | Total score | 1 day after completion of open treatment phase |
| App recorded ratings of auditory verbal hallucinations (AVH) | 5 times a day randomized time points for app ratings of AVH | From first day of open treatment phase, and through one week after completion of treatment |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |