Abstract
Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.
Highlights
Schizophrenia is a severe and frequent mental disorder usually characterized by negative, positive and disorganization symptoms.Negative symptoms of schizophrenia (NSS) classically include affective flattening or blunting, alogia, asociality, anhedonia and avolition
Effects of intermittent theta burst transcranial magnetic stimulation (iTBS) on negative symptoms Repeated measures analysis of variance (ANOVA) on Scale for the Assessment of Negative Symptoms (SANS) scores revealed a significant interaction between time and group (F(3,60) = 3.32, p = 0.026)
We investigated the clinical and biological effects of iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) on NSS
Summary
Schizophrenia is a severe and frequent mental disorder usually characterized by negative, positive and disorganization symptoms.Negative symptoms of schizophrenia (NSS) classically include affective flattening or blunting, alogia, asociality, anhedonia and avolition. At a structural level, imaging studies have reported that the volume of prefrontal regions, including orbitofrontal, medial and lateral prefrontal cortices, was inversely correlated with NSS severity[5,6]. A white matter volume decrease was observed in prefrontal areas in patients with NSS and was associated with higher levels of NSS7. Studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT) found that NSS were strongly associated with decreased frontal and prefrontal metabolism at rest or during activation[8,9]. More recent studies have suggested that patients with NSS have structural and functional impairments in prefrontal areas and that the connectivity between those areas and the rest of the brain, including striatal regions, is impacted[11]
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