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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
46
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.
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
Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials
Uppsala, Sweden
Amplitude on EEG in speech-listen task
Neurophysiological outcome of the blinded cross-over phase
Time frame: 5-30 minutes after intervention
Change on The Psychotic Symptom Rating Scales (PSYRATS)
Auditory Verbal Hallucination symptom interview, total score
Time frame: 1 day after completion of open treatment phase
Finger tapping test
Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
Time frame: 5-30 minutes after intervention
Double step saccade-task
Performance (Zimmermann et al Sci Rep, 2018).
Time frame: 20-60 minutes after intervention
Resting state functional magnetic resonance imaging (rsfMRI)
Resting state SMA connectivity change as measured with fMRI
Time frame: 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.
Time frame: 1 day after completion of open treatment phase
Brief Psychiatric Rating Scale (BPRS)
Total score
Time frame: 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
Time frame: From first day of open treatment phase, and through one week after completion of treatment
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