Abstract
Obsessive compulsive disorder (OCD) and major depressive disorder (MDD) are common, often refractory, neuropsychiatric conditions for which new treatment approaches are urgently needed. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel surgical technique permitting incisionless ablative neurosurgery. We examined the safety profile, clinical response, and imaging correlates of MRgFUS bilateral anterior capsulotomy in patients with refractory obsessive compulsive disorder (OCD, Nā=ā6) and major depressive disorder (MDD, nā=ā6). There were no serious adverse events. Nonserious adverse events included headaches and pin-site swelling in 7/12 patients. The response rate was 4/6 and 2/6 in the OCD and MDD cohorts respectively. To delineate the white-matter tracts impacted by capsulotomy, a normative diffusion MRI-based structural connectome was used, revealing tracts terminating primarily in the frontal pole, medial thalamus, striatum, and medial-temporal lobe. Positron emission tomography (PET) analysis (nine subjects) revealed widespread decreases in metabolism bilaterally in the cerebral hemispheres at 6 months post treatment, as well as in the right hippocampus, amygdala, and putamen. A pretreatment seed-to-voxel resting-state functional magnetic resonance imaging (rs-fMRI) analysis (12 subjects) revealed three voxel clusters significantly associated with eventual clinical response. MRgFUS capsulotomy appears to be safe, well tolerated, and according to these initial results, may be an important treatment option for patients with refractory OCD and MDD. MRgFUS capsulotomy results in both targeted and widespread changes in neural activity, and neuroimaging may hold potential for the prediction of outcome.
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References
Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:617ā27.
Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53ā63.
Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep. 2018;8:2861.
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905ā17.
Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment. JAMA 2017;317:1358ā67.
Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014;65:977ā87.
Torres AR, Ramos-Cerqueira AT, Ferrao YA, Fontenelle LF, do Rosario MC, Miguel EC. Suicidality in obsessive-compulsive disorder: prevalence and relation to symptom dimensions and comorbid conditions. J Clin Psychiatry. 2011;72:17ā26.
Pepper J, Zrinzo L, Hariz M. Anterior capsulotomy for obsessive-compulsive disorder: a review of old and new literature. J Neurosurg. 2019:1ā10.
Rasmussen SA, Noren G, Greenberg BD, Marsland R, McLaughlin NC, Malloy PJ, et al. Gamma ventral capsulotomy in intractable obsessive-compulsive disorder. Biol Psychiatry. 2018;84:355ā64.
Ruck C, Karlsson A, Steele JD, Edman G, Meyerson BA, Ericson K, et al. Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients. Arch Gen Psychiatry. 2008;65:914ā21.
Christmas D, Eljamel MS, Butler S, Hazari H, MacVicar R, Steele JD, et al. Long term outcome of thermal anterior capsulotomy for chronic, treatment refractory depression. J Neurol Neurosurg Psychiatry. 2011;82:594ā600.
Subramanian L, Bracht T, Jenkins P, Choppin S, Linden DE, Phillips G, et al. Clinical improvements following bilateral anterior capsulotomy in treatment-resistant depression. Psychol Med. 2017;47:1097ā106.
Pepper J, Hariz M, Zrinzo L. Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature. J Neurosurg. 2015;122:1028ā37.
Lopes AC, Greenberg BD, Canteras MM, Batistuzzo MC, Hoexter MQ, Gentil AF, et al. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71:1066ā76.
Widge AS, Malone DA Jr., Dougherty DD. Closing the loop on deep brain stimulation for treatment-resistant depression. Front Neurosci. 2018;12:175.
Arya S, Filkowski MM, Nanda P, Sheth SA. Deep brain stimulation for obsessive-compulsive disorder. Bull Menninger Clin. 2019;83:84ā96.
Davidson B, Meng Y, Giacobbe P, Hamani C, Lipsman N. Magnetic resonance-guided focused ultrasound for psychiatric disorders. Clin Pharmacol Ther. 2019;106:720ā2.
Krishna V, Sammartino F, Rezai A. A review of the current therapies, challenges, and future directions of transcranial focused ultrasound technology: advances in diagnosis and treatment. JAMA Neurol. 2018;75:246ā54.
Kim M, Kim CH, Jung HH, Kim SJ, Chang JW. Treatment of major depressive disorder via magnetic resonance-guided focused ultrasound surgery. Biol Psychiatry. 2018;83:e17ā8.
Kim SJ, Roh D, Jung HH, Chang WS, Kim CH, Chang JW. A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up. J Psychiatry Neurosci. 2018;43:327ā37.
Ravikumar VK, Parker JJ, Hornbeck TS, Santini VE, Pauly KB, Wintermark M, et al. Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Mov Disord. 2017;32:1165ā73.
Li C, Gajic-Veljanoski O, Schaink AK, Higgins C, Fasano A, Sikich N, et al. Cost-effectiveness of magnetic resonance-guided focused ultrasound for essential tremor. Mov Disord. 2019;34:735ā43.
Mindus P, Rasmussen SA, Lindquist C. Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function. J Neuropsychiatry Clin Neurosci. 1994;6:467ā77.
Talairach JHH, David M. Lobotomie prĆ©frontale limitĆ©e par Ć©lectrocoagulation des fibres thalamo-frontales Ć leur Ć©mergence du bras antĆ©rieur de la capsule interne. Rev Neurol. 1949;83:59.
Su L, Cai Y, Xu Y, Dutt A, Shi S, Bramon E. Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies. BMC Psychiatry. 2014;14:321.
Macpherson T, Hikida T. Role of basal ganglia neurocircuitry in the pathology of psychiatric disorders. Psychiatry Clin Neurosci. 2019;73:289ā301.
Kopell BH, Greenberg BD. Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry. Neurosci Biobehav Rev. 2008;32:408ā22.
Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. https://doi.org/10.1186/1471-244X-14-S1-S1.
Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, et al. The yale-brown obsessive compulsive scale. II. validity. Arch Gen Psychiatry. 1989;46:1012ā6.
Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967;6:278ā96.
Endicott J, Nee J, Harrison W, Blumenthal R. Quality of life enjoyment and satisfaction questionnaire: a new measure. Psychopharmacol Bull. 1993;29:321ā6.
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382ā9.
Beck AT, Steer RA. Internal consistencies of the original and revised Beck Depression Inventory. J Clin Psychol. 1984;40:1365ā7.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168:1266ā77.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429ā35.
Wechsler D. Wechsler test of adult reading: WTAR. San Antonio, TX: the Psychological Corporation; 2001.
Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test-Second Edition (CVLT-II). San Antonio, TX: Psychological Corporation; 2000.
Benedict RHB, Schretlen D, Groninger L, Dobraski M, Shpritz B. Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and validity. Psychological Assess. 1996;8:145ā53.
Fine EM, Delis DC. DelisāKaplan executive functioning system. In: Kreutzer JS, DeLuca J, Caplan B, editors. Encyclopedia of clinical neuropsychology. New York, NY: Springer; 2011. p. 796ā801.
Smith A. Symbol digit modalities test: manual. Los Angeles: Western Psychological Services; 1982.
Stout JC, Ready RE, Grace J, Malloy PF, Paulsen JS. Factor analysis of the frontal systems behavior scale (FrSBe). Assessment. 2003;10:79ā85.
Jung HH, Kim SJ, Roh D, Chang JG, Chang WS, Kweon EJ, et al. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry. 2015;20:1205ā11.
Miguel EC, Lopes AC, McLaughlin NCR, Noren G, Gentil AF, Hamani C, et al. Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder. Mol Psychiatry. 2019;24:218ā40.
Lipsman N, Mainprize TG, Schwartz ML, Hynynen K, Lozano AM. Intracranial applications of magnetic resonance-guided focused ultrasound. Neurotherapeutics. 2014;11:593ā605.
Chang WS, Jung HH, Zadicario E, Rachmilevitch I, Tlusty T, Vitek S, et al. Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull. J Neurosurg. 2016;124:411ā6.
Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54:2033ā44.
Yeh FC, Tseng WY. NTU-90: a high angular resolution brain atlas constructed by q-space diffeomorphic reconstruction. Neuroimage. 2011;58:91ā9.
Desikan RS, Segonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31:968ā80.
Greve DN, Svarer C, Fisher PM, Feng L, Hansen AE, Baare W, et al. Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data. Neuroimage. 2014;92:225ā36.
Greve DN, Salat DH, Bowen SL, Izquierdo-Garcia D, Schultz AP, Catana C, et al. Different partial volume correction methods lead to different conclusions: an (18)F-FDG-PET study of aging. Neuroimage. 2016;132:334ā43.
Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2012;2:125ā41.
Yin D, Zhang C, Lv Q, Chen X, Zeljic K, Gong H, et al. Dissociable frontostriatal connectivity: mechanism and predictor of the clinical efficacy of capsulotomy in obsessive-compulsive disorder. Biol Psychiatry. 2018;84:926ā36.
Ruck C, Edman G, Asberg M, Svanborg P. Long-term changes in self-reported personality following capsulotomy in anxiety patients. Nordic J Psychiatry. 2006;60:486ā91.
Kumar KK, Bhati MT, Ravikumar VK, Ghanouni P, Stein SC, Halpern CH. MR-guided focused ultrasound versus radiofrequency capsulotomy for treatment-refractory obsessive-compulsive disorder: a cost-effectiveness threshold analysis. Front Neurosci. 2019;13:66.
Hurwitz TA, Honey CR, Allen J, Gosselin C, Hewko R, Martzke J, et al. Bilateral anterior capsulotomy for intractable depression. J Neuropsychiatry Clin Neurosci. 2012;24:176ā82.
Zhan S, Liu W, Li D, Pan S, Pan Y, Li Y, et al. Long-term follow-up of bilateral anterior capsulotomy in patients with refractory obsessive-compulsive disorder. Clin Neurol Neurosurg. 2014;119:91ā5.
Liu K, Zhang H, Liu C, Guan Y, Lang L, Cheng Y, et al. Stereotactic treatment of refractory obsessive compulsive disorder by bilateral capsulotomy with 3 years follow-up. J Clin Neurosci. 2008;15:622ā9.
Suetens K, Nuttin B, Gabriels L, Van Laere K. Differences in metabolic network modulation between capsulotomy and deep-brain stimulation for refractory obsessive-compulsive disorder. J Nucl Med. 2014;55:951ā9.
Riestra AR, Aguilar J, Zambito G, Galindo y Villa G, Barrios F, Garcia C, et al. Unilateral right anterior capsulotomy for refractory major depression with comorbid obsessive-compulsive disorder. Neurocase. 2011;17:491ā500.
Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525ā49.
Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR Jr. Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry. 2003;160:522ā32.
Vaghi MM, Vertes PE, Kitzbichler MG, Apergis-Schoute AM, van der Flier FE, Fineberg NA, et al. Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: evidence from resting-state functional connectivity. Biol Psychiatry. 2017;81:708ā17.
Quevedo K, Ng R, Scott H, Kodavaganti S, Smyda G, Diwadkar V, et al. Ventral striatum functional connectivity during rewards and losses and symptomatology in depressed patients. Biol Psychol. 2017;123:62ā73.
Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry. 2004;61:34ā41.
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999;156:675ā82.
Dunlop BW, Mayberg HS. Neuroimaging-based biomarkers for treatment selection in major depressive disorder. Dialogues Clin Neurosci. 2014;16:479ā90.
Wang Q, Tian S, Tang H, Liu X, Yan R, Hua L, et al. Identification of major depressive disorder and prediction of treatment response using functional connectivity between the prefrontal cortices and subgenual anterior cingulate: A real-world study. J Affect Disord. 2019;252:365ā72.
Sun H, Jiang R, Qi S, Narr KL, Wade BS, Upston J, et al. Preliminary prediction of individual response to electroconvulsive therapy using whole-brain functional magnetic resonance imaging data. Neuroimage Clin. 2019:102080.
Boutet A, Gwun D, Gramer R, Ranjan M, Elias GJB, Tilden D, et al. The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound. J Neurosurg. 2019:1ā7.
Hughes A, Huang Y, Schwartz ML, Hynynen K. The reduction in treatment efficiency at high acoustic powers during MR-guided transcranial focused ultrasound thalamotomy for essential tremor. Med Phys. 2018;45:2925ā36.
Funding
This study was funded by the Focused Ultrasound Foundation, the Harquail Centre for Neuromodulation, and philanthropic support toĀ the Sunnybrook Foundation.
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Davidson, B., Hamani, C., Rabin, J.S. et al. Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: clinical and imaging results from two phase I trials. Mol Psychiatry 25, 1946ā1957 (2020). https://doi.org/10.1038/s41380-020-0737-1
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DOI: https://doi.org/10.1038/s41380-020-0737-1
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