Introduction: Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim).

Methods: The study included a cohort of 17 consecutive ET patients treated only with left unilateral SRS-T between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (standard deviation 2.7, 0.2-10). Neuroimaging data were collected at baseline (n=17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH) were completed pretherapeutically and 1 year later. We further correlate these scores with baseline connectivity in twenty major large-scale brain networks.

Results: We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus1, bilateral thalamus interconnected with motor cerebellum lobule V2 (ADL) and anterior default-mode network interconnected with Brodmann area 103 (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (p>0.05). The same applied to pretherapeutic tremor scores, after using the same methodology described above.

Conclusions: Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) inter-connectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy (SRS-T).

Patient Care: Based on the present report, one could perform a resting-state fMRI study, with minimal patient compliance, taking 10 minutes time and be able to anticipate the clinical result one year after stereotactic radiosurgical thalamotomy.

Learning Objectives: By the conclusion of the session, participants should be able to: 1- describe the importance of resting-state fMRI in characterizing neurological diseases and not only 2- understand the role of the curent surgical treatments for tremor 3- identify which pretherapeutic brain networks functional connectivity would be able to predict tremor recovery after thalamotomy

References: 1. Louis ED. Essential tremor. The Lancet. Neurology. Feb 2005;4(2):100-110. 2. Benito-Leon J, Louis ED, Romero JP, et al. Altered Functional Connectivity in Essential Tremor: A Resting-State fMRI Study. Medicine. Dec 2015;94(49):e1936. 3. Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB. Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic study. Archives of neurology. Jun 2005;62(6):1004-1007. 4. Deuschl G, Elble R. Essential tremor--neurodegenerative or nondegenerative disease towards a working definition of ET. Movement disorders : official journal of the Movement Disorder Society. Oct 30 2009;24(14):2033-2041. 5. Sharifi S, Nederveen AJ, Booij J, van Rootselaar AF. Neuroimaging essentials in essential tremor: a systematic review. NeuroImage. Clinical. 2014;5:217-231. 6. Hubble JP, Busenbark KL, Wilkinson S, et al. Effects of thalamic deep brain stimulation based on tremor type and diagnosis. Movement disorders : official journal of the Movement Disorder Society. May 1997;12(3):337-341. 7. Louis ED. Treatment of Medically Refractory Essential Tremor. The New England journal of medicine. Aug 25 2016;375(8):792-793. 8. Benabid AL, Pollak P, Gao D, et al. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. Journal of neurosurgery. Feb 1996;84(2):203-214. 9. Witjas T, Carron R, Azulay JP, Regis J. Gammaknife Thamamotomy For Intractable Tremors: Clinical Outcome And Correlations With Neuroimaging Features. Paper presented at: MDS 17th International Congress of Parkinson's Disease and Movement Disorders2013. 10. Lipsman N, Schwartz ML, Huang Y, et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. The Lancet. Neurology. May 2013;12(5):462-468. 11. Horn A, Reich M, Vorwerk J, et al. Connectivity Predicts deep brain stimulation outcome in Parkinson disease. Annals of neurology. Jul 2017;82(1):67-78. 12. Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic resonance in medicine. Oct 1995;34(4):537-541. 13. Kondziolka D, Ong JG, Lee JY, Moore RY, Flickinger JC, Lunsford LD. Gamma Knife thalamotomy for essential tremor. Journal of neurosurgery. Jan 2008;108(1):111-117. 14. Bain PG, Findley LJ, Atchison P, et al. Assessing tremor severity. Journal of neurology, neurosurgery, and psychiatry. Aug 1993;56(8):868-873. 15. Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. Parkinson’s Disease and Movement Disorders: Baltimore: Urban and Schwarzenberg; 1988:225–234. 16. Witjas T, Carron R, Krack P, et al. A prospective single-blind study of Gamma Knife thalamotomy for tremor. Neurology. Nov 03 2015;85(18):1562-1568. 17. Guiot G, Arfel G, Derome P, Kahn A. [Neurophysiologic control procedures for sterotaxic thalamotomy]. Neuro-Chirurgie. May 1968;14(4):553-566. 18. Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE. Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage. Feb 01 2012;59(3):2142-2154. 19. Van Dijk KR, Sabuncu MR, Buckner RL. The influence of head motion on intrinsic functional connectivity MRI. NeuroImage. Jan 02 2012;59(1):431-438. 20. Calhoun VD, Adali T, Pearlson GD, Pekar JJ. A method for making group inferences from functional MRI data using independent component analysis. Human brain mapping. Nov 2001;14(3):140-151. 21. Stone JV. Independent component analysis: an introduction. Trends in cognitive sciences. Feb 01 2002;6(2):59-64. 22. Regis J, Carron R, Park M. Is radiosurgery a neuromodulation therapy? : A 2009 Fabrikant award lecture. Journal of neuro-oncology. Jun 2010;98(2):155-162. 23. Lenfeldt N, Holmlund H, Larsson A, Birgander R, Forsgren L. Frontal white matter injuries predestine gait difficulties in Parkinson's disease. Acta neurologica Scandinavica. Sep 2016;134(3):210-218. 24. Buijink AW, van der Stouwe AM, Broersma M, et al. Motor network disruption in essential tremor: a functional and effective connectivity study. Brain : a journal of neurology. Oct 2015;138(Pt 10):2934-2947. 25. Li X, Zhuang P, Hallett M, Zhang Y, Li J, Li Y. Subthalamic oscillatory activity in parkinsonian patients with off-period dystonia. Acta neurologica Scandinavica. Nov 2016;134(5):327-338. 26. Louis ED, Babij R, Cortes E, Vonsattel JP, Faust PL. The inferior olivary nucleus: a postmortem study of essential tremor cases versus controls. Movement disorders : official journal of the Movement Disorder Society. Jun 2013;28(6):779-786. 27. Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Annals of neurology. Oct 1994;36(4):636-642. 28. Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH. Activation mapping in essential tremor with functional magnetic resonance imaging. Annals of neurology. Jan 1997;41(1):32-40. 29. Hesselmann V, Maarouf M, Hunsche S, et al. Functional MRI for immediate monitoring stereotactic thalamotomy in a patient with essential tremor. European radiology. Oct 2006;16(10):2229-2233. 30. De Zeeuw CI, Simpson JI, Hoogenraad CC, Galjart N, Koekkoek SK, Ruigrok TJ. Microcircuitry and function of the inferior olive. Trends in neurosciences. Sep 1998;21(9):391-400. 31. Marr D. A theory of cerebellar cortex. The Journal of physiology. Jun 1969;202(2):437-470. 32. Welsh JP, Lang EJ, Suglhara I, Llinas R. Dynamic organization of motor control within the olivocerebellar system. Nature. Mar 30 1995;374(6521):453-457. 33. Yarom Y, Cohen D. The olivocerebellar system as a generator of temporal patterns. Annals of the New York Academy of Sciences. Dec 2002;978:122-134. 34. Goldman MS, Ahlskog JE, Kelly PJ. The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor. Journal of neurosurgery. Jun 1992;76(6):924-928. 35. Campbell AM, Glover J, Chiang VL, Gerrard J, Yu JB. Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: a systematic review of the literature. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. Mar 2015;114(3):296-301. 36. Fang W, Chen H, Wang H, et al. Essential tremor is associated with disruption of functional connectivity in the ventral intermediate Nucleus--Motor Cortex--Cerebellum circuit. Human brain mapping. Jan 2016;37(1):165-178. 37. Hua SE, Lenz FA. Posture-related oscillations in human cerebellar thalamus in essential tremor are enabled by voluntary motor circuits. Journal of neurophysiology. Jan 2005;93(1):117-127. 38. Schnitzler A, Munks C, Butz M, Timmermann L, Gross J. Synchronized brain network associated with essential tremor as revealed by magnetoencephalography. Movement disorders : official journal of the Movement Disorder Society. Aug 15 2009;24(11):1629-1635. 39. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage. Jan 15 2009;44(2):489-501. 40. Semendeferi K, Armstrong E, Schleicher A, Zilles K, Van Hoesen GW. Prefrontal cortex in humans and apes: a comparative study of area 10. American journal of physical anthropology. Mar 2001;114(3):224-241. 41. Ramnani N, Owen AM. Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nature reviews. Neuroscience. Mar 2004;5(3):184-194. 42. Gilbert SJ, Frith CD, Burgess PW. Involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent thought. The European journal of neuroscience. Mar 2005;21(5):1423-1431.