T79. INTERMITTENT THETA BURST STIMULATION OF CEREBELLAR VERMIS IN SCHIZOPHRENIA: IMPACT ON NEGATIVE SYMPTOMS AND BRAIN CONNECTIVITY

Abstract

Background: Negative symptoms and cognitive deficits are a substantial cause of disability in schizophrenia, and are often resistant to conventional methods of treatment necessitating newer therapies. Theta Burst Stimulation or TBS, a novel form of Transcranial Magnetic Stimulation (TMS) has more potent and long‐lasting effects than conventional rTMS (repetitive TMS). TBS when delivered to novel brain targets (e.g., the cerebellar vermis) has shown promising results in open‐label trials. Methods: A double blind randomised controlled trial (Trial Registration. No‐REF/2016/09/012196) was conducted where we randomized 60 schizophrenia patients with persistent negative symptoms, to receive intermittent TBS (iTBS; n=30) or sham TBS (n=30). In iTBS a burst of three pulses is administered at 50 Hz, repeated at a frequency of 5 Hz and delivered in 2 s trains followed by an 8 s interval. They received 600‐pulses of neuronavigation‐ guided cerebellar vermis TBS (area VIIB) twice daily, four hours apart for five days, with an intensity of 80% of active motor threshold. Patients underwent assessments of positive and negative symptoms, depression, extrapyramidal symptoms and cognition at baseline, sixth‐day and six‐weeks after the intervention. Resting state functional magnetic resonance imaging was performed at baseline and on the sixth‐day after intervention. Results: Mixed‐models repeated measures analysis showed significant time effect for negative symptoms (Scale for Assessment of Negative Symptoms total score; F= 37.433, P<0.001), i.e. improvement in both the arms, but no significant group∗time interaction (F=0.630, p=0.536). There was no significant difference in change in cognitive functions between the two groups. Two patients belonging to the iTBS arm showed symptoms of hypomania/ mania during the intervention, which subsided subsequently. Seed Based Analysis (FMRIB Software Library) demonstrated increased connectivity between the cerebellar vermis area VIIB and the right superior and middle frontal gyri and frontal pole after the course of iTBS (798 voxels, p cluster‐ FWE = 0.016). There was no significant change in resting state functional connectivity in the sham group. Discussion: Both, active and sham cerebellar‐iTBS improved negative symptoms in this sample; however, the active treatment resulted in significant increase in functional connectivity between the cerebellum and the right prefrontal cortex ‐ an important circuit underlying negative symptoms of schizophrenia. Future trials may examine modified stimulation and delivery settings like number of sessions, number of pulses per session, intensity of stimulation etc to generate improvement beyond the observed placebo response.