Cognitive Flexibility and Response to TMS Therapy

Transcranial Magnetic Stimulation (TMS) therapy is an approved and effective treatment option for treatment-resistant obsessive-compulsive disorder. The present study aims to investigate the relationship between cognitive flexibility and TMS treatment. The main question it aims to answer is:

Does cognitive flexibility predict the TMS treatment response rate? Patients will undergo neuropsychological tests to evaluate cognitive flexibility before the TMS application. A clinical scale to assess the severity of obsessive-compulsive symptoms will be administered using psychometric scales both before and after the TMS procedure.

TMS treatment will be applied five days a week for four weeks.

This prospective cohort study aims to investigate the relationship between transcranial magnetic stimulation (TMS) and cognitive flexibility in patients with treatment-resistant obsessive-compulsive disorder (OCD). Treatment-resistant OCD represents a subset of OCD in which patients do not adequately respond to conventional treatments such as cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). Emerging evidence suggests that TMS, a noninvasive brain stimulation technique, can effectively alleviate symptoms in treatment-resistant OCD. However, its relationship with cognitive flexibility remains poorly understood.

This study seeks to fill this knowledge gap by assessing cognitive flexibility before TMS treatment to identify patients cognitively suitable for this intervention and understand how they respond to TMS. Another important factor to be investigated is whether there are differences between TMS responders and non-responders.

The study will enroll 30 patients diagnosed with treatment-resistant obsessive-compulsive disorder (OCD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Participants will undergo a TMS treatment treatment using the MagVenture™ X100™ device. The treatment protocol will include 20 sessions over four weeks, delivering a total of 24.000 pulses.

The stimulation will target the supplementary motor area (SMA), a region associated with OCD symptom regulation, with parameters optimized to achieve therapeutic effects while minimizing adverse side effects. Motor threshold measurements will be conducted prior to the initiation of treatment and adjusted weekly to ensure consistent treatment intensity.

A control group of 60 healthy participants will undergo a single neuropsychological evaluation for baseline comparison but will not receive TMS treatment or follow-up.

Comprehensive neuropsychological and clinical psychometric assessments will be conducted for all patients prior to the TMS treatment. After completing the 20 sessions of TMS treatment, patients will undergo clinical psychometric evaluations again.

The neuropsychological assessments will include the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Verbal Fluency (VF) test. Psychiatric assessments will utilize the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Patient Health Questionnaire (PHQ-9), and Clinical Global Impression-Improvement (CGI-I) scale to evaluate changes in the severity of OCD symptoms.

The primary objective is to determine whether cognitive flexibility in OCD patients plays a role in predicting the response to TMS treatment. Secondary objectives include identifying any differences in cognitive flexibility test results between TMS responders and non-responders.

The primary outcomes will focus on whether cognitive flexibility-defined as the ability to adapt and cope with stress-affects the outcome of TMS treatment. This is particularly important for identifying patients who are likely to benefit from this time-intensive and prolonged treatment. Knowing in advance which patients are unlikely to respond to TMS treatment could help guide them toward alternative therapies, benefiting both patients and physicians.

Additionally, although TMS is highly effective for OCD treatment, literature suggests that up to half of patients do not respond. Understanding whether these non-responders are cognitively inflexible could help identify specific cognitive subtypes of OCD patients. This knowledge would be invaluable for tailoring treatments and improving outcomes for this challenging subset of patients.

Eligibility Criteria:
Inclusion Criteria:

* According to the DSM-5 TR, those diagnosed with Obsessive-Compulsive Disorder (OCD),
* Failure to respond to at least two different antidepressants and anti-obsessive agents at effective doses and durations,
* The condition cannot be better explained by a metabolic or organic disorder,
* No contraindications to treatment were identified based on the risk assessment scale applied before TMS.

Exclusion Criteria:

* Detection of a contraindication for treatment based on the pre-TMS risk assessment form,
* Detection of an epileptic focus in the pre-TMS electroencephalography findings,
* Diagnosis of a psychotic disorder or bipolar mood disorder,
* Active suicidal thoughts and high risk for suicide,
* The participant to be included in the study has a history of alcohol, substance, or stimulant abuse or addiction (excluding cases where they have not used these substances in the last 12 months or have no history of alcohol misuse), based on a semi-structured clinical interview.