Mapping symptom-general and symptom-specific targets for transcranial magnetic stimulation in schizophrenia: an electric-field modeling meta-analysis

Article Article scientifique Article Mapping symptom-general and symptom-specific targets for transcranial magnetic stimulation in schizophrenia: an electric-field modeling meta-analysis eng 2025-09-22 author Sinanaj Lorina 428022 Département de psychiatrie (PSYAT) author Pallis Konstantinos 959287 author Fazel Dehkordi Anahita 900344 author Huguelet Philippe 32349 Département de psychiatrie (PSYAT) author Kaiser Stefan 0000-0002-3013-2034 868946 Département de psychiatrie (PSYAT) author Bègue Indrit http://orcid.org/0000-0001-5350-4454 715639 Département de psychiatrie (PSYAT) 10.1038/s41380-025-03238-z 40983650 1359-4184 https://www.nature.com/articles/s41380-025-03238-z Negative, positive, and cognitive symptoms of schizophrenia relate to disruptions in partially distinct brain circuits. Although promising, transcranial magnetic stimulation (TMS) strategies across and within symptom domains remain to be established due to TMS protocol heterogeneity. For this, we combined standard meta-analysis with electric field (E-field) modeling to identify stimulation sites where E-field strength was associated most significantly with clinical improvement. Standard meta-analysis of randomized, sham-controlled studies in 4283 patients demonstrated the benefit of TMS across symptom domains, regardless of target or protocol. TMS significantly improved negative and cognitive symptoms with high-frequency stimulation applied to the left prefrontal cortex, whereas positive symptoms improved with low-frequency TMS applied to the left temporoparietal cortex. In-depth examination of these results with E-field modeling identified stimulation of the left dorsomedial prefrontal cortex (L-DMPFC), left orbitofrontal cortex (L-OFC), and left cerebellar crus II and right lobule IX to be significantly associated with improvement across all symptom domains. Greater overlap of studies’ stimulation targets with L-DMPFC and L-OFC related to improved outcomes. For negative symptoms, E-field distribution in L-DMPFC and L-OFC related most significantly to clinical improvement. Greater proximity to L-DMPFC stimulation site indicated better outcomes, with trend-level significance for L-OFC. In the cognitive domain, E-field distribution in the left dorsolateral prefrontal cortex was related to clinical improvement. Finally, the strongest E-field association with clinical improvement was found in the right cerebellar lobules VIIIA, VIIIB, and IX for positive symptoms. These results support symptom-general and symptom-specific TMS approaches for distinct therapeutic goals towards personalized neuromodulation in schizophrenia. Dewey 616.89 60 Département de psychiatrie 225 false 1236 Psychopathologie clinique et expérimentale 987 1431 Neuroimagerie et psychiatrie translationnelle 1058 416 Psychiatrie communautaire 688 https://github.com/lorinas/metaModeling Molecular psychiatry 33652eee-8b1c-475f-a9d0-4bd8c3fe2509 Article (Published version) Public Article_scientifique_from_crossref.pdf 3608376 application/pdf CC BY-4.0 01588c27b9501977ec1658e00ed7b73a95ff768a2dd949bdab8f970ae1d1c1e0 d5e26f16-131a-4136-865e-a3e2c1c98f31 Supplemental data Public 41380_2025_3238_MOESM1_ESM.docx 2640302 application/vnd.openxmlformats-officedocument.wordprocessingml.document dc03b95f28fd93d2c415986b20e98edac534bf64d8964506f49c59fbdd46385b 1aa7e999-7a85-4b0c-8791-7ff068b46b29 Supplemental data Public 41380_2025_3238_MOESM2_ESM.xlsx 18899 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 3b874c24801c88a435e4518634fd128daf0b20572a827ac84c2accdd87a6c2c6 1b5fe1c3-0865-419e-920d-8b7497e9ba96 Supplemental data Public 41380_2025_3238_MOESM3_ESM.xlsx 37256 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet a9ede80e3ee90ad130791421084971a9de161d6e3bf973a59051edac0c2d306b bcfb77b1-36f2-4ab6-8179-7e7c57f0cd00 Supplemental data Public 41380_2025_3238_MOESM4_ESM.xlsx 17469 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet f17f867f8805a2fd906e0577bedf4ba8890bb748b1eb3319cae58a7ef43f58f6 openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Mapping symptom-general and symptom-specific targets for transcranial magnetic stimulation in schizophrenia: an electric-field modeling meta-analysis	Molecular psychiatry			2025	66	48

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Fazel Dehkordi, Anahita