Personalized Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: Impact of Cognitive Flexibility on Treatment Outcomes

Abstract

This systematic review evaluates the current evidence on the relationship between cognitive flexibility and transcranial magnetic stimulation (TMS) efficacy in Obsessive-compulsive disorder (OCD). Specifically, the potential of cognitive flexibility to serve as a neuropsychological marker capable of predicting treatment response and the potential of personalized TMS protocols developed on this basis to enhance therapeutic efficacy were investigated.A comprehensive search of PubMed, Scopus, and Google Scholar was conducted to identify clinical trials and observational studies examining both cognitive flexibility and response to TMS. Studies utilizing standardized neuropsychological measures such as the Wisconsin Card Sorting Test, Trail Making Test, and Verbal Fluency tasks were included. Results suggest that cognitive flexibility may play a moderating role in treatment outcomes, with about half of the reviewed studies reporting a positive association between higher cognitive flexibility and improved TMS response. Nevertheless, discrepancies across studies—particularly in assessment tools and stimulation protocols—limit the ability to draw firm conclusions. In conclusion, cognitive flexibility appears to be a potentially important factor in enhancing the effectiveness of TMS for OCD.

Keywords

• Obsessive-compulsive disorder
• transcranial magnetic stimulation
• cognitive flexibility
• neuromodulation
• executive function
• personalized treatment.

Obsesif-Kompulsif Bozuklukta Kişiselleştirilmiş Transkraniyal Manyetik Uyarım: Bilişsel Esnekliğin Tedavi Sonuçlarına Etkisi

Öz

Bu sistematik derleme, Obsesif-kompulsif bozukluk (OKB) hastalarında bilişsel esneklik ile ranskraniyal manyetik stimülasyon (TMS) tedavisinin etkinliği arasındaki ilişkiyi incelemektedir. Özellikle bilişsel esnekliğin, tedavi yanıtını öngörebilecek bir nöropsikolojik belirteç olup olamayacağı ve bu temelde geliştirilecek kişiselleştirilmiş TMS protokollerinin terapötik etkinliği artırma potansiyeli araştırılmıştır. PubMed, Scopus ve Google Scholar veri tabanlarında yapılan sistematik tarama ile, OKB’de bilişsel esneklik ve TMS tedavi yanıtını değerlendiren klinik deneyler ve gözlemsel çalışmalar belirlenmiştir. Wisconsin Kart Eşleme Testi, İz Sürme Testi ve Sözel Akıcılık Testi gibi standart nöropsikolojik araçları kullanan çalışmalar incelemeye alınmıştır. Bulgular, incelenen çalışmaların yaklaşık yarısında yüksek bilişsel esneklik düzeylerinin daha iyi TMS yanıtı ile pozitif yönde ilişkili olduğunu göstermektedir. Ancak bazı çalışmalarda bu ilişki doğrulanamamış; bu farklılıklar, kullanılan bilişsel değerlendirme yöntemleri ve TMS protokollerindeki metodolojik çeşitlilikle açıklanabilir. Sonuç olarak, bilişsel esneklik TMS uygulamalarının OKB tedavisinde optimize edilmesinde önemli bir faktör olabilir; ancak bu ilişkinin altında yatan mekanizmalar henüz tam olarak aydınlatılamamıştır.

Anahtar Kelimeler

• *Obsesif-Kompulsif Bozukluk
• Transkraniyal Magnetik Stimülasyon
• Bilişsel Esneklik
• Nöromodülasyon
• Yürütücü İşlev
• Kişiselleştirilmiş Tedavi*

References

1. Abramovitch A, McCormack B, Brunner D, Johnson M, Wofford N (2019) The impact of symptom severity on cognitive function in obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev, 67:36-44.
2. Acevedo N, Bosanac P, Pikoos T, Rossell S, Castle D (2021) Therapeutic neurostimulation in obsessive-compulsive and related disorders: a systematic review. Brain Sci, 11:94-98.
3. Ahmari SE, Rauch SL (2022) The prefrontal cortex and obsessive compulsive disorder. Neuropsychopharmacology, 47:211-224.
4. Ansari EM, Talesh JA, Niyasar AR, Rostami R, Khosrowabadi R (2025) Altered brain network stability in obsessive compulsive disorder following repetitive transcranial magnetic stimulation intervention: insights from structural balance theory. Psychiatry Res Neuroimaging, 346:1119-11127.
5. Baldi S, Schuhmann T, Goossens L, Schruers KRJ (2024) Individualized, connectome-based, non-invasive stimulation of obsessive compulsive disorder deep-brain targets: a proof-of-concept. Neuroimage, 288:1205-1227.
6. Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H et al. (2019) Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: a prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry, 176:931-938.
7. Cintoli S, Favilli L, Morganti R, Siciliano G, Ceravolo R, Tognoni G 2024) Verbal fluency patterns associated with the amnestic conversion from mild cognitive impairment to dementia. Sci Rep,14:20-29.
8. Çelik S, Oğuz M, Konur U, Köktürk F, Atasoy N (2021) Comparison of computerized and manual versions of the wisconsin card sorting test on schizophrenia and healthy samples. Psychol Assess, 33:562-567.

9. Dehghani AF, Kazemi R, Hallajian AH, Sima S, Boutimaz S, Hedayati S et al. (2024) Koushamoghadam S, Safarifard R, Salehinejad MA. Meta-analysis of repetitive transcranial magnetic stimulation efficacy for obsessive compulsive disorder treatment. J Clin Med, 13:53-58.
10. Garip B (2024) Cognitive flexibility and response to TMS therapy (CogFlexTMS). ClinicalTrials.gov identifier: NCT06769243. Updated 10.01.2025. https://clinicaltrials.gov/study/NCT06769243 (Accessed 20.03.2025).
11. Grassi G, Moradei C, Cecchelli C (2023) Will transcranial magnetic stimulation improve the treatment of obsessive-compulsive disorder? a systematic review and meta-analysis of current targets and clinical evidence. Life, 13:1494.
12. Gruner P, Pittenger C (2016) Cognitive inflexibility in obsessive-compulsive disorder. Neuroscience, 345:243-255.
13. Jalal B, Chamberlain SR, Sahakian BJ (2023) Obsessive-compulsive disorder: etiology, neuropathology, and cognitive dysfunction. Brain Behav,13:e3000.
14. Lange F, Seer C, Kopp B (2017) Cognitive flexibility in neurological disorders: cognitive components and event-related potentials. Neurosci Biobehav Rev, 83:496-507.
15. Laskov O, Klírová M (2021) Effects of deep transcranial magnetic stimulation on cognition. Neurosci Lett, 755:135906.
16. Manarte L, Andrade AR, do Rosário L, Sampaio D, Figueira ML, Morgado P et al. (2021a) Executive functions and insight in obsessive compulsive disorder: a comparative study. BMC Psychiatry, 21:216.
17. Manarte L, Andrade AR, do Rosário L, Sampaio D, Figueira ML, Langley C et al. (2021b) Poor insight in obsessive compulsive disorder: associations with empathic concern and emotion recognition. Psychiatry Res, 304:114-129.
18. Miles S, Howlett CA, Berryman C, Nedeljkovic M, Moseley GL, Phillipou A (2021) Considerations for using the wisconsin card sorting test to assess cognitive flexibility. Behav Res Methods, 53:2083-2091.
19. Neu P, Gooren T, Niebuhr U, Schlattmann P (2019) Cognitive impairment in schizophrenia and depression: a comparison of stability and course. Appl Neuropsychol Adult, 26:215-228.
20. Park I, Ha M, Kim T, Lho SK, Moon SY, Kim M et al. (2023) Cortical gyrification differences between early- and late-onset obsessive-compulsive disorder: neurobiological evidence for neurodevelopmentally distinct subtypes. Psychol Med, 53:5976-5985.
21. Pellegrini L, Clarke A, Fineberg NA, Laws KR (2024) The inflexible mind: a critical factor in understanding and addressing covid-19 vaccine hesitancy. J Psychiatr Res, 179:360-365.
22. Rosa-Alcázar Á, Olivares-Olivares PJ, Martínez-Esparza IC, Parada-Navas JL, Rosa-Alcázar AI, Olivares-Rodríguez J (2020) Cognitive flexibility and response inhibition in patients with obsessive-compulsive disorder and generalized anxiety disorder. Int J Clin Health Psychol, 20:20-28.
23. Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmöller J et al. (2021) Safety and recommendations for transcranial magnetic stimulation use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol, 132:269-306.
24. Sachse EM, Widge AS (2025) Neurostimulation to improve cognitive flexibility. Curr Opin Behav Sci, 62:101484.
25. Schwert C, Stohrer M, Aschenbrenner S, Weisbrod M, Schröder A (2019) Biased neurocognitive self-perception in depression - what is the reason for the discrepancy? J Affect Disord, 243:193.
26. Shayganfard M, Jahangard L, Nazaribadie M, Haghighi M, Ahmadpanah M, Sadeghi Bahmani D et al. (2016) Repetitive transcranial magnetic stimulation improved symptoms of obsessive-compulsive disorders but not executive functions: results from a randomized clinical trial with crossover design and sham condition. Neuropsychobiology. 74:115-124.
27. Şahin H, Köşger F, Eşsizoğlu A, Aksaray G (2018) The relationship between obsessive belief level and cognitive flexibility in patients with obsessive compulsive disorder. Noro Psikiyatr Ars, 55:376-379.
28. Tomiyama H, Nakao T, Murayama K, Nemoto K, Ikari K, Yamada S etal. (2019) Dysfunction between dorsal caudate and salience network associated with impaired cognitive flexibility in obsessive-compulsive disorder: a resting-state functional magnetic resonance imaging study. Neuroimage Clin, 24:102004.
29. Vaghi MM, Vértes PE, Kitzbichler MG, Apergis-Schoute AM, van der Flier FE, Fineberg NA et al. (2017) Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: evidence from resting-state functional connectivity. Biol Psychiatry, 81:708-717.
30. Xu J, Huang T, Dana A (2023) Deep brain stimulation of the subthalamic nucleus to improve symptoms and cognitive functions in patients with refractory obsessive-compulsive disorder: a longitudinal study. Neurol Sci. 44:2385-2392.
31. Yun JY, Jang JH, Jung WH, Shin NY, Kim SN, Hwang JY et al. (2017) Executive dysfunction in obsessive-compulsive disorder and anterior cingulate-based resting state functional connectivity. Psychiatry Investig, 14:333-343