Safety And Efficacy Of Magnetic Resonance Imaging-Based And Robot-Assisted Accelerated Transcranial Magnetic Stimulation On Suicidal Ideation In Major Depressive Disorder

BackgroundMajor depressive disorder(MDD)is a mental illness with high prevalence,and mortality.More than half of the patients have significant suicidal ideation,which is a heavy burden to patients as well as society.Therefore,MDD with suicidal ideation(MDD-SI)is recognized as a global public issue,calling for more effective interventions.The brain network mechanism of MDD-SI is not clear,and there is a lack of rapid,effective,convenient and safety interventions.Repetitive transcranial magnetic stimulation(r TMS)is an emerging neuromodulation technique that has been recommended by multiple guidelines for the treatment of MDD.Accelerated TMS,such as Stanford neuromodulation therapy(SNT),shows great potential to shorten treatment time and improve treatment efficacy.However,the efficacy of SNT on MDD-SI is not yet clear.The optimal stimulating parameters of accelerated protocol still need to be explored.And the mechanism of accelerated remains to be clarified.ObjectiveStudy 1: The current study aimed to clarify the safety and efficacy of TMS robot-assisted SNT in the treatment of MDD-SI.Study 2: To investigate the possible mechanism of SNT based on functional magnetic resonance imaging.MethodsStudy 1: We conducted a small sample and open label exploratory study and recruited 32 patients with MDD-SI to receive SNT(10 sessions of 1800-pulse i TBS per day with 50-min interval for 5 consecutive days).The stimulation intensity was set at 90% of the resting motor threshold(rMT).Based on individual f MRI data,the stimulating target was located at the region of left DLPFC most anti-correlated with sgACC.The stimulation was delivered by TMS neuro-navigated robot.The severity of suicidal ideation and depressive symptoms were assessed by Beck scale for suicide ideation-Chinese version(BSI-CV)and 17-item Hamilton depression scale(HAMD-17)/Montgomery-Asberg depression rating scale(MADRS)respectively at baseline,post 5-day treatment,2-week and 4-week after treatments.The Perceived Deficit Questionnaire for Depression(PDQ-D),Digit Span Test(DST)and Digit Symbol Substitution Test(DSST)were used to assess cognitive function at baseline and post 5-day treatment.Study 2: f MRI data were collected from patients with MDD-SI in study 1 before and after treatments and 25 healthy controls.We compared resting functional connectivity between MDD-SI and HC,pre-and post-treatment.ResultsStudy 1: Repeated measures ANOVA showed a significant reduction in BSI-CV scores at each time points after treatments.After 5-day treatment,the score of BSI-CV decreased significantly,the mean score decreased by 11.50(95%CI: 8.88-14.12),with a response and remission rates of 65.63% and 56.25%.The mean score of HAMD-17 decreased by 18.53(95%CI:15.72-21.34),with a response and remission rates of 81.25% and 53.13%.The response and remission rates were 90.63% and 56.25%,96.88% and 81.25% at 2-week and4-week after treatments,respectively.There were no serious adverse events during the study period.The most common adverse effects in treatments were headache and tingling at the site of stimulating.The scores of DST(t =-6.155,P<0.001)and DSST(t =-6.550,P<0.001)were significantly higher than baseline and PDQ scores were significantly lower than baseline(t = 6.054,P<0.001).Study 2: Compared with healthy controls,the functional connectivity between visual network(VN)and default mode network(DMN),frontal-parietal network(FPN)in MDDSI decreased most significantly.The functional connectivity between sensorimotor network(SMN)and FPN /affective network(AN),FPN and AN also decreased significantly.The activity of the middle temporal gyrus of MDD-SI was abnormally activated compared with HC.After treatment,the activity of occipital gyrus decreased significantly in BSIresponders.ConclusionStudy 1: TMS robot-assisted SNT,delivered to left DLPFC most anti-correlated with sgACC,can rapidly alleviate suicidal ideation and depressive symptoms.And SNT was safe and tolerable,with no cognitive and serious side effects.Study 2: Patients with MDD-SI showed a decreased functional connectivity among multiple brain networks.The integration of the sensory circuit(e.g.VN)and the cognitive decision-making circuit(e.g.DMN and FPN)may be an important neurobiological basis for suicidal ideation.SNT may play a role in rapidly relieving suicidal ideation through modulating the function of the visual cortex remotely.