rTMS Tuukka RaijMD PhD title of docent in psychiatry Helsinki and Uusimaa Hospital Districttuukkaraijhusfi Disclosures Research funding from the Finnish State ID: 1000608
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1. Overview of fMRI targeted rTMSTuukka Raij/MD, PhD, title of docent in psychiatryHelsinki and Uusimaa Hospital District/tuukka.raij@hus.fi
2. DisclosuresResearch funding from the Finnish State research funding, the Academy of Finland, the Finnish Cultural Foundation
3. MotivationrTMS is recommended in major quidelines for treatment of medication-resistant depressionMinimal side effects (Wang et al J Affective Disorders 2022)Can be relatively accurately targeted to a brain region of interestHowever, only about 1/5 may achieve remission (Berlim et al Psychol Med 2014; Sehatzadeh et al J Psych Neurosci 2019)
4. Suboptimal targeting may contribute to suboptimal efficacyTMS-induced action potentials may be restricted to few cm2 of the cortex (Nudo et al J Neurosci 1996; Romero et al Nat Communications 2019)Functional targets may differ centimeters between individuals within DLPFC (Fox et al Neuroimage 2013; Weigand et al Biol Psych 2018; Cash et al iol Psych 2019 and JAMA Psych 2020)
5. Functional magnetic resonance imagingMost common functional imaging method in brain researchHundreds of fast images with MR-signal that reflects blood oxygenation levelTells about neuronal activitySpatial resolution few mm
6. Functional connectivity Fox et al reported 2012 that targets functionally negatively connected to the sugenual anterior cingulate cortex (sgACC) associate with good outcome (Biol psychiatry)
7. Replicated two times at individual levelCash et al Biol Psychiatry 2018Weigand et al Biol Psychiatry 2019The stronger (negative) connectivity between sgACC and TMS-target, the larger response to treatment
8. Distance of TMS target from the individual sgACC negative connectivity maximum also correlates with the treatment response (Cash ym JAMA Psychiatry 2020)
9. Is fmri reliable enough for clinical use?fmri-signal from sgACC is prone to artifacts and is noisy (Ning et al Brain stimul 2019)Resulting connectivity maps are poorly repeatableReproducibility can be enhanced by reducing resolution of images (smoothing or clustering; Ning et al 2019; Cash et al HBM 2021) or selecting multiple regions instead of sgACC only to compute connectivity (Fox et al 2013)fmri session 1 = bluefmri session 2 = green
10. Increasing knowledge about depression-related networks can be used to construct connectivity networks instead of sgACC onlyWilliams. Lancet Psy 2016
11. Helsinki network connectivity modelImproved repeatability about 5-fold compared to sgACC connectivity (Raij et al to be submitted)29 depression patientsfmri session 1 = bluefmri session 2 = green
12. Correlated with severity of depression symptoms before TMS and with decrease of symptoms during TMS (Raij et al to be submitted)
13. Targets still differed about 2 cm between individuals
14. Hitting targetsIndividual head models can be used to match the individual TMS-induced electrical activity with target With help of neuronavigation devicesStenroos and Koponen Neuroimage 2019
15. Clinical trials with fMRI connectivity targeting
16. sgACC-connectivity targeting in Stanford Neuromodulation TreatmentRandomized comparison against sham-stimulation suggested good efficacy N = 29, selected sample, large number of treatment sessions (50 in one wk), no comparison against targeting as usualPhillips et al Am J Psychiatry 2021
17. Helsinki network model targetingPilot findings promisingOpen and blind in small samplesLarger randomized studies ongoingNMNMUsual TMS
18. BRIGhTMIND study255 patients randomized in UK to receive TMS as usual or TMS targeted based on fmri connectivity of right insula.Data collection ended in Jan 2022https://institutemh.org.uk/research/projects-and-studies/current-studies/brightmind
19. ConclusionsTMS can be targeted to individual functional networksAdvances in imaging methods may produce clinically useful targets in the near futureUtility of such targeting depends on cost-benefit
20. Thank You!In collaboration with Erkki Isometsä, Emma Komulainen, personnel of Helsinki neuromodulation units (HUS and University of Helsinki), Matti Stenroos, Siina Pamilo (Aalto University), Baran Aydogan (University of Eastern Finland), Tommi Raij (Harvard University)
21. Finnish prime minister Kalevi Sorsa 1975