Differences in Metabolic Network Modulation Between Capsulotomy and Deep-Brain Stimulation for Refractory Obsessive-Compulsive Disorder
Open accessAbstract
UNLABELLED: Around 7%-10% of patients with obsessive-compulsive disorder (OCD) are refractory to first-line treatment. Neurosurgical approaches are available such as capsulotomy or deep-brain stimulation (DBS). There is strong evidence for central involvement of the corticostriatopallidothalamocortical (CSPTC) circuit in OCD, but the exact mechanism through which these interventions lead to clinical improvement and potential differences in network modulation are not fully understood. METHODS: In total, 13 capsulotomy patients (aged 29-59 y, 10 men and 3 women) and 16 DBS patients (aged 25-56 y, 6 men and 10 women) were prospectively included. (18)F-FDG PET was performed before and after capsulotomy and before and after DBS in both stimulation-on and stimulation-off conditions. Presurgical scans were compared with scans of healthy volunteers using SPM8 and global scaling, and metabolic changes after DBS were compared with changes after capsulotomy. Correlations with clinical improvements were investigated using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: Both groups had similar pretreatment clinical morbidity as assessed by Y-BOCS and the Hamilton Depression Rating Scale. Preoperative superior frontal and supplementary motor cortex hypometabolism was common to both patient groups, and the subgenual anterior cingulate, occipital cortex (cuneus), and posterior cerebellum were relatively hypermetabolic. Postoperative metabolic decreases were common to both interventions in the anterior cingulate and the prefrontal and orbitofrontal cortices. Compared with DBS, capsulotomy resulted in more intense metabolic changes, with additional significant decreases in the mediodorsal thalamus, caudate nucleus, and cerebellum as well as increases in the precuneus and the fusiform and lingual gyrus. The stimulation-off condition of DBS patients showed no significant differences from the preoperative state. Improvement in Y-BOCS scores correlated with metabolic changes in the occipital cortex. Baseline metabolism in the subgenual anterior cingulate and superior temporal cortices were related to postoperative improvement of depressive symptoms. CONCLUSION: Capsulotomy and DBS lead to similar clinical improvement and similar metabolic network changes in the CSPTC circuit, with a prominent role for the subgenual anterior cingulate and other core structures of the CSPTC. However, metabolic changes are more pronounced and extended in capsulotomy than in DBS. Furthermore, cortical regions outside the CSPTC may also play an important role in OCD symptomatology.
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Chronic stimulation in the ALIC/BST area induced metabolic decreases in the anterior cingulate cortex and in the prefrontal and orbitofrontal cortices, i.e. changes in components of the cortico-striato-thalamo-cortical loops.
“Chronic stimulation in the ALIC/BST area induced changes in components of the corticostriato-thalamo-cortical loops, that is, metabolic decreases in the anterior cingulate cortex (which was elevated preoperatively as compared with healthy subjects) and in the prefrontal and orbitofrontal cortices.”
From Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder (2016) · cites this paper as [38]
In these patients the anterior cingulate cortex was elevated preoperatively as compared with healthy subjects.
“metabolic decreases in the anterior cingulate cortex (which was elevated preoperatively as compared with healthy subjects)”
From Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder (2016) · cites this paper as [38]
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Ma, J., Wang, C., Huang, P. C., Wang, X., Shi, L.-J., Li, H., Sang, D., Kou, S., Li, Z., Zhao, H., et al. (2021) · Brain and Behavior · doi:10.1002/brb3.2059 · Cited by 11 · see citing works
“Also, capsulotomy and deepbrain stimulation lead to similar clinical improvement and increase metabolism in fusiform and lingual gyrus (Suetens et al., 2014).”
BackgroundServaes, S., Glorie, D., Verhaeghe, J. A. J., Wyffels, L., Stroobants, S. G., & Staelens, S. G. (2016) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2016.10.003 · Cited by 11 · see citing works
“Although involvement of these regions in the manifestation of OCD is beyond doubt, reports of hyperactivity have not been consistent throughout studies (Agarwal et al., 2013; Suetens et al., 2014), making interpretation and treatment evaluation difficult.”
Neuroablative Intervention for Refractory Obsessive-Compulsive Disorder
Chang, J. G., Kim, S. J., & Kim, C. (2023) · Psychiatry Investigation · doi:10.30773/pi.2023.0214 · Cited by 10 · see citing works
Allam, A. K., Giridharan, N., Hasen, M., Banks, G. P., Reyes, G., Dang, H., Kabotyanski, K. E., Hertz, A. G., Heilbronner, S. R., Provenza, N. R., et al. (2024) · Journal of Neurosurgery Case Lessons · doi:10.3171/case24289 · Cited by 8 · see citing works
“30 However, DBS regulates cortical tracts in a more complex manner through both orthodromic and antidromic stimulation.”
Abdulbaki, A., Masri, J. E., Ghazi, M., Kahl, K. G., Mocking, R. J. T., Salameh, P., Schuurman, R., Nuttin, B., & Krauss, J. K. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116651 · Cited by 7 · see citing works
Self-citationThirty Years of Global Deep Brain Stimulation: “Plus ça change, plus c’est la même chose”?
Hariz, M., Cif, L., & Blomstedt, P. (2023) · Stereotactic and Functional Neurosurgery · doi:10.1159/000533430 · Cited by 5 · see citing works
“These imaging modalities have been applied in surgery for movement disorders [58 – 61] and for psychiatric illnesses [62, 63].”
BackgroundMethodNuclear medicine of the cerebellum
Vella, A., & Mascalchi, M. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63956-1.00015-1 · Cited by 7 · see citing works
New Directions for Surgical Ablation Treatment of Obsessive Compulsive Disorder
Etherington, L. V., Matthews, K., & Akram, H. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_207 · Cited by 6 · see citing works
Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning
Lv, Q., Zeljic, K., Zhao, S., Zhang, J., Zhang, J., & Wang, Z. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01057-2 · Cited by 5 · see citing works
“Furthermore, bilateral capsulotomy has been reported to alter metabolic activity in the dorsal ACC, OFC, IFG, medial dorsal thalamus, caudate, and cerebellum [79, 80].”
BackgroundAcevedo, N., Castle, D. J., & Rossell, S. L. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2306875 · Cited by 5 · see citing works
Fanty, L., Yu, J., Chen, N., Fletcher, D. B., Hey, G. E., Okun, M. S., & Wong, J. K. (2023) · Expert Review of Medical Devices · doi:10.1080/17434440.2023.2252732 · Cited by 5 · see citing works
“Reduction of OCB and concurrent depression were found to be comparable to those of anterior capsulotomies [62].”
ResultNeurocircuits commonly involved in psychiatric disorders and their stimulation and lesion therapies
Heilbronner, S. R., Safadi, Z., & Haber, S. N. (2015) · doi:10.1002/9781118801086.ch3 · Cited by 5 · see citing works
Xue, T., Qiu, Y., Li, X., Xie, M., Wang, W., Chen, Z., Xie, H., Bai, Y., Yang, A., Meng, F., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-025-03438-7 · Cited by 3 · see citing works
Chaves, L. P., Souza, Á. R., da Silva, L. J., Crivellaro, L. D. L., & da Silva, M. F. (2021) · Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery · doi:10.1055/s-0041-1731013 · Cited by 3 · see citing works
Renaissance for anterior capsulotomy for obsessive–compulsive disorder?
Hariz, M. I. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2021-328121 · Cited by 2 · see citing works
Deep Brain Stimulation: The Perspective of Brain Connectivity
Kim, H. Y. (2016) · InTech eBooks · doi:10.5772/62829
PET and SPECT Imaging of Non-pharmacological Interventions for Psychiatric Disorders
Doma, A. (2014) · Springer eBooks · doi:10.1007/978-3-642-40384-2_35
Neuromodulation for Psychiatric Disorders
Hescham, S., Tönge, M., Jahanshahi, A., & Temel, Y. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-800454-8.00014-8
Neurosurgery for Obsessive-Compulsive Disorder: Indications and Procedures
Lopes, A. C. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108164313.022
Kahn, D. A. (2018) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000302
Obsessive Compulsive Disorder: Neurobiology and Treatment
Hoffman, K. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00161-4
PET and SPECT Imaging of Non-pharmacological Interventions for Psychiatric Disorders
Doma, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-57231-0_34
Minnerop, M. (2023) · Springer eBooks · doi:10.1007/978-3-031-15070-8_51
Davidson, B. P., Clappison, A., Mithani, K., Bocca, L. F., Giacobbe, P., Nestor, S. M., Meng, Y., Ottoy, J., Rabin, J. S., Burke, M., et al. (2026) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2026.01.011
Boone, L., Shafie, M., Naeem, A., Yang, D., Germann, J., Bai, Y., Goubran, M., Hamani, C., Lipsman, N., Tang, V. M., et al. (2026) · NeuroImage Clinical · doi:10.1016/j.nicl.2026.103976
Deep Brain Stimulation for Psychiatric Disorders: A Systematic Review of Molecular Imaging with PET
Patil, S., Gerlach, A. D. M., Jeevika, F., Patel, R. K. P., Christner, E., Gujral, J., Gandhi, O. H., Writer, M., Wang, N. M., Kopylova, A., et al. (2026) · World Neurosurgery · doi:10.1016/j.wneu.2026.124933
Neural basis of successful DBS for OCD after failed capsulotomyPreprint
Ryan, M. A., Jammal, R. E., Soubra, S. S., Paulo, D. F., Bentley, J. H., Hamre, T. A., Giridharan, N., Suzuki, H., Arroyave, N. V., Storch, E. A., et al. (2026) · medRxiv · doi:10.64898/2026.06.08.26355178
Neurobiology-informed treatment approaches for obsessive–compulsive disorder
Kawtharani, S., Shouman, W. A., Issa, D. A., Nitturi, V., Giridharan, N., Paulo, D. L., Merk, T., Provenza, N. R., Storch, E. A., Goodman, W. K., et al. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27446-6.00007-8
- Authors
- Suetens, K., Nuttin, B., Gabriëls, L., & Van Laere, K.
- Affiliations
- KU Leuven (BE)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2014-04-10
- Volume
- 55
- Issue
- 6
- Pages
- 951-959
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2125285320
- Cited by
- 64
- References
- 40
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 2 · 2021: 12 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 3 · 2016: 2 · 2015: 8 · 2014: 1
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- refractory obsessive-compulsive disorder, capsulotomy, deep brain stimulation, brain metabolism, FDG-PET, superior frontal cortex, supplementary motor area, occipital cortex, mediodorsal thalamus, caudate nucleus, cerebellum, depressive symptoms
- MeSH terms
- Adult, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Postoperative Period, Treatment Failure, Neurosurgical Procedures, Deep Brain Stimulation, Positron-Emission Tomography, Metabolic Networks and Pathways
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