The objective of this study is to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on the symptoms and cognitive function of patients with schizophrenia.
Research Article
The objective of this study is to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on the symptoms and cognitive function of patients with schizophrenia.
Cognitive impairment is a core symptom of schizophrenia, severely affecting patients’ prognosis and quality of life. Repetitive transcranial magnetic stimulation (rTMS) and occupational therapy (OT) show potential efficacy alone, while their combined effects on cognitive function remain to be explored. A retrospective analysis was conducted on 131 hospitalized schizophrenia patients from September 2024 to June 2025. Based on the treatment regimens documented in their medical records, patients were divided into two groups: cohort A (n=67), who received only regular drug treatment and psychological rehabilitation; and cohort B (n=64), who received additional rTMS combined with OT. The Positive and Negative Symptom Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (rBANS) scores were collected at baseline, week 4, and week 8. Independent t-tests, chi-square tests, repeated-measures analysis of variance, and linear regression were used to compare differences in symptoms and cognitive function between cohorts and across time points, to assess symptom and cognitive function improvement. There was no significant difference in general data, initial scores of PANSS and rBANS between the two cohorts (P > 0.05). After 4 weeks and 8 weeks of treatment, the total scores of PANSS in both cohorts were significantly decreased (P < 0.05), and the total scores of rBANS were significantly increased (P < 0.05) compared with week 0/4, where cohort B had a larger change than cohort A (P < 0.05). Moreover, after 8 weeks of treatment, there were significant differences in all subscale scores of PANSS and rBANS between cohort B and cohort A (P < 0.05). In summary, rTMS combined with OT is able to improve the symptoms and cognitive function in schizophrenia patients. Moreover, the effect of an 8-week intervention is greater than that of a 4-week intervention.
Schizophrenia is a set of severe mental disorders with unknown causes, characterized by abnormal functions in cognition, thinking and emotion, and leading to significant impairments in occupational and social functions1. A latest data analysis found that the incidence rate of schizophrenia has increased by 37% in the past 20 years2. The Global Burden of Disease Study showed that there were approximately 23.6 million prevalent cases of schizophrenia worldwide in 20193. Schizophrenia patients suffer from positive symptoms (for example, auditory hallucinations) and negative symptoms (for example, flattening of affect), which are correlated to their brain functional abnormality1. Apart from psychotic symptoms including positive and negative symptoms, most patients with schizophrenia also have severe cognitive dysfunction, which mainly manifested as attention disorders, decreased working memory, degeneration of executive and control function, and reduced speech function, etc.4 Cognitive dysfunction or cognitive impairment has always been regarded as a core characteristic of schizophrenia5, for cognitive dysfunction is significantly associated with other poor outcomes, as illustrated by a 20-year follow-up study6. Cognitive decline runs through the entire stage of schizophrenia, which can begin before the onset of psychosis and can last for more than 10 years7. In consideration of the strong association between cognitive function and psychosocial function8, improving cognitive function is an essential part in the treatment of schizophrenia.
Pharmacotherapies are cornerstones of the management of schizophrenia, and antipsychotics is the first-line treatment of schizophrenia9, yet most current antipsychotics show minimal effects on improving cognitive functions when they are used solely. Even positive symptoms may be effectively relieved after antipsychotic drug treatment, the functional outcomes of patients with schizophrenia are still disappointing10. Despite the deficiency in cognition-improving drugs, additional methods to target the improvement of cognition and restore individual function have been developed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation approach that utilizes alternating magnetic fields to modulate electrical currents in localized cortical tissue11, with proven efficacy on auditory hallucinations and negative symptoms, and recommended for schizophrenia patients12. While there were several studies exploring the effects of rTMS on schizophrenia12, the parameters they used were heterogeneous, and the results were controversial. Moreover, most of them focused on rTMS only, leaving the potential synergistic effects between rTMS and other sociopsychological therapies understudied. Occupational therapy (OT) is an integrated non-pharmacological intervention, using structured and meaningful activities to reduce limitations in schizophrenia patients and improve their quality of life13, with psychosocial, psychoeducational, cognitive, and exercise beneficial effects. OT can contribute to improvement in social functioning by influencing social cognition, motivation, self-efficacy, dysfunctional attitudes, and everyday life skills14.
Although rTMS and OT have each demonstrated efficacy in improving symptoms and cognitive function in schizophrenia, no study to date has investigated the potential synergistic effects of combining them. rTMS targets neurophysiological dysfunction through direct cortical modulation, while OT facilitates the functional application of cognitive gains in daily life contexts. We hypothesized that combining rTMS with OT would produce greater improvements in both psychotic symptoms and cognitive function compared to pharmacotherapy alone, and longer intervention time (8 weeks vs 4 weeks) would yield superior outcomes. Ideal treatments for schizophrenia may combine pharmacological approaches with cognitive remediation15. Therefore, this study aimed to evaluate the efficacy of rTMS combined with OT in a retrospective cohort of hospitalized schizophrenia patients, to inform comprehensive cognitive rehabitation strategies that integrate neurostimulation with occupation-based interventions in schizophrenia.
Access restricted. Please log in or start a trial to view this content.
This study was approved by the Ethics Committee of Yichun Third People's Hospital (Approval No.202445).
Participants Characteristics and Allocation
The data of 131 schizophrenia patients with stable conditions who were hospitalized in the Yichun Third People's Hospital from September 2024 to June 2025 were retrospectively collected and analyzed. Based on the treatment regimens documented in their medical records, patients were divided into two groups. Patients who received only pharmacological treatment and standard psychological rehabilitation were assigned to cohort A (n = 67), while those who additionally underwent rTMS combined with occupational therapy were assigned to cohort B (n = 64). The decision to provide combined therapy was made by the attending physicians based on clinical judgment and patient preferences, not by the study investigators, therefore, the allocation was not influenced by the investigators.
Inclusion criteria: (1) Inpatients who met the ICD-10 diagnostic criteria for schizophrenia F20. (2) Patients with no obvious abnormalities found in the general examination and physical examination. (3) Patients aged 18–60 years old, with basically normal intellectual development, and at least 5 years of education. (4) Patients in their stable or recovery period of schizophrenia. (5) Patients with informed consent available.
Exclusion criteria: (1) Patients with a hospital admission and stay duration less than 8 weeks; (2) Patients with severe physical diseases, those with metal implants in their bodies, were pregnant women, patients with intracranial hypertension, a history or family history of epilepsy; (3) Patients who abuse psychoactive substances such as alcohol and drugs; (4) Patients with other severe mental disorders, mental retardation, and dementia; (5) Patients who are currently undergoing or preparing to undergo other clinical studies.
Therapeutic method
Patients were allocated to two cohorts based on the interventions they received during hospitalization as documented in their medical records. Cohort A (n = 67) comprised patients who received only regular drug treatment and psychological rehabilitation. Cohort B (n = 64) consisted of patients who, in addition to regular drug treatment and psychological rehabilitation, also received rTMS combined with OT.
Regular drug treatment and psychological rehabilitation: All patients were given a single second-generation antipsychotic drug treatment, with the type determined by their attending physicians. During the treatment period, the original treatment drug remained unchanged, and the dosage could be adjusted within the regular dose for 8 weeks. The decision of drug types and dose adjustments were made according to the same criteria across all patients. The types of drug were similar in the two cohorts, as shown in Table 1. Standard psychological rehabilitation consisted of weekly psychoeducation sessions, supportive counseling, and basic illness management guidance provided for all patients by psychiatric nurses or clinical psychologists for 8 consecutive weeks. Psychoeducation sessions covering the nature of schizophrenia, the role of antipsychotic medications and adherence were delivered in a structured group format (8–10 patients per group). Supportive counceling focused on adaptive coping, validation of patients’ experiences, and assistance with daily problem-solving, which was delivered in individual formats. Guidance on illness management include medication self-management, symptom self-monitoring, and relapse prevention.
rTMS: rTMS intervention was given according to the rTMS evidence-based guidelines12 and the conclusions of meta-analysis16, which support the use of high-frequency stimulation at intensities ranging from 80% to 110% of the individual resting motor threshold (RMT) for optimal therapeutic effects on negative symptoms and cognitive function in schizophrenia17. Low intervention frequency, intervention time over 20 min, and intervention period of 4 weeks are also recommended16. Prior to the first session, each patients was informed about the procedure and positioned comfortably in a reclining chair. A swim cap was placed on the patient’s head to allow marking of stimulation sites for consistent coil placement across sessions. A magnetic stimulator equipped with a figure-of-eight coil is adopted for its better focusing performance and sensitivity to coil handle orientation. Each patient's RMT was determined prior to the first session, by positioning the coil over the left motor cortex to identify the optimal site for eliciting motor evoked potentials (MEPs) in the contralateral right abductor pollicis brevis muscle. RMT was defined as the minimum stimulation intensity required to induce MEPs of ≥ 50 µV peak-to-peak amplitude in at least 5 out of 10 consecutive trials. Stimulation targets were localized using the international 10–20 EEG system: the left dorsolateral prefrontal cortex (DLPFC) at the F3 electrode position, and the right DLPFC at the F4 electrode position. The coil position was marked on the swim cap to ensure consistent placement across sessions.The stimulation intensity was set individually based on each patient’s RMT, with the range of 80% to 110%, and was adjusted within this range based on patient tolerance and clinical response: treatment typically began at 80% RMT and could be gradually increased up to 110% RMT if well tolerated, in accordance with clinical protocols that prioritize both safety and therapeutic efficacy17,18. Each session consisted of two sequential stimulation phases: first, right DLPFC stimulation at 2 Hz frequency, with 10-second trains and 5-second inter-train intervals, delivering 800 pulses; second, left DLPFC stimulation at 10 Hz frequency, with 2-second trains and 20-second inter-train intervals, delivering 1000 pulses. The asymmetric pulse counts corresponded to the different stimulation frequencies applied to each hemisphere, and the sequential bilateral approach was chosen based on evidence that bilateral stimulation may produce greater therapeutic effects on negative symptoms and cognitive function compared to unilateral stimulation alone19. Total stimulation time was 28 min and 20 s, with additional setup time resulting in approximately 30–35 min per session. Sessions were administered five times per week for 8 consecutive weeks. Throughout each session, patients were monitored for any discomfort or adverse effects.
OT: Occupational therapy was delivered by certified occupational therapists in group sessions (6–8 patients per group), five times per week for 8 consecutive weeks. Each session lasted 120 min, starting with 15 min of group warm-up and session goal-setting, and followed by 90 min of structured engagement in meaningful occupations across three domains: Activities of daily living training, including meal preparation, budgeting, personal care routines, medication management, and household organization tasks; productive activities, such as simulated vocational tasks (e.g., assembling simple products, clerical work), workshop-based activities, and gardening; creative and leisure activities, including calligraphy and painting, craftwork (e.g., jewelry making, textile work), group games, and cultural activities (e.g., music, poetry reading). The session ended with 15 min of group reflection and feedback session, where patients shared their experiences and therapists provided individualized feedback on performance and goal achievement. The activity selection was guided by the Model of Human Occupation framework, with activities tailored to each patient's occupational profile, interests, and functional level. Therapists used structured observation to assess patients' occupational performance (engagement, task completion, and social interaction) and documented progress using a standardized session rating form. Engagement was measured as the duration (min) of continuous task engagement without significant distraction or need for redirection; task completion was defined as the proportion of task steps successfully completed within the allotted time, based on task-specific step-by-step checklists; social interaction was rated on a 5-point Likert scale across initiation, reciprocity, and cooperation, with scores summed to yield a total ranging from 1–15. The measurable parameters were recorded immediately following the sessions. When patients could engage and complete the whole task independently with a social interaction score > 8, they were encouraged to progress from simpler to more complex activities based on their individual improvement.
Outcome Assessment
General patient information such as age, gender, years of education, course of disease, and drug type was retrospectively collected. Course of disease, namely, duration of illness, was defined as the time elapsed (in years) from the date of first schizophrenia diagnosis to the date of study enrollment, as documented in patients' medical records. Antipsychotic medication type was recorded from patients' medical records as the primary second-generation antipsychotic administered during the hospitalization period. Based on the documented prescriptions, drug type was classified into four categories: olanzapine, risperidone, aripiprazole, and others (including quetiapine, paliperidone, etc.). The symptoms and cognitive functions of the patients were evaluated before treatment (week 0), 4 weeks after treatment (week 4), and 8 weeks after treatment (week 8).
For investigating the psychotic symptoms of the patients, the Positive and Negative Syndrome Scale (PANSS) were utilized. The PANSS scale is widely used in the symptom assessment of schizophrenia patients in clinical practice worldwide. It includes 30 items, including three sub-scales: positive symptoms, negative symptoms, and general psychopathology. Each scale contains 7, 7, and 16 questions respectively. The higher the score, the more severe the mental symptoms of the patient. This study used the Chinese version of the PANSS scale20, which was proved with good reliability and validity21. The improvement score was calculated as (PANSS total score before treatment - PANSS total score after treatment) / PANSS total score before treatment x 100%. The improvement in psychotic symptoms was defined as ‘recovery’ when the improvement score is ≥ 75%, ‘effective’ when the improvement score is ≥ 50% but less than 75%, ‘progress’ when the improvement score is ≥ 25% and less than 50%, ‘ineffective’ when the improvement score is less than 25%.
The Repeatable Battery for the Assessment of Neuropsychological Status (rBANS) was utilized to measure the cognitive function of schizophrenia patients. It was developed by Randolph et al.22, and mainly used to assess the cognitive function of patients with mental illness. rBANS consists of 12 items, five groups of neuropsychological states, namely immediate memory, visuospatial construction, language, attention, and delayed memory. The higher the score, the better the cognitive function of the patient is indicated. The Chinese version of the rBANS scale was used23, and scaled scores with a normal mean of 100 and standard deviation of 15 were used for evaluation. An rBANS total score ≥ 115 indicates good cognitive function better than others; a total score between 85 to 115 indicates no obvious impairment in cognitive function found; a total score between 70 to 85 indicates mild cognitive function impairment; a total score < 70 indicates obvious cognitive function impairment.
The scales were all evaluated by two attending physicians. Training was provided before the evaluation, and the standards were unified. The two attending physicians who conducted the PANSS and rBANS assessments were blinded to patients' group allocation. They had access only to the patients' medical record numbers and assessment schedules, but not to information regarding whether patients had received additional rTMS and occupational therapy. The raters were also unaware of the study hypotheses. All assessment data were collected and recorded using coded patient identifiers, and group assignment was revealed only after the final database was locked. The consistency coefficient Kappa between the evaluators was 0.87. The scale scores were entered into the database and then reviewed by a dedicated person.
Statistical methods
Statistical software was used for the statistical analyses including descriptive analysis, independent t-tests, chi-square tests, repeated-measures analysis of variance (ANOVA), and linear regression. The primary focus of the repeated-measures ANOVA was to examine the main effects of time and group with their interaction, therefore, post hoc pairwise comparisons across time points were not central to our research objectives, and therefore no multiple-comparison corrections were applied. Data visualization software was used for data visualization. Quantitative data were expressed in and t-tests were used in statistical tests for difference. Enumeration data were expressed in their count number (n) with percent (%) and -tests were used in statistical tests for difference. All assumptions for parametric analyses were evaluated. Normality was assessed using the Shapiro-Wilk test, and sphericity was tested using Mauchly's test; where the sphericity assumption was violated, Greenhouse-Geisser corrections were applied. Partial eta-squared (η2) values indicate small (η2 ≈ 0.01), medium (η2 ≈ 0.06), or large (η2 ≥ 0.14) effects respectively according to conventional benchmarks. All statistical tests were two-tailed probability tests, α = 0.05. Statistics with P < 0.05 were regarded as statistically significant.
All primary analyses (repeated-measures ANOVA, linear regression) were performed using rBANS total scores as continuous variables. For descriptive purposes only, rBANS total scores were also categorized according to established clinical thresholds to provide an intuitive overview of cognitive function distribution between cohorts at each time point. No inferential statistical tests were conducted on these categorical groupings.
In regression analyses, drug type was treated as a categorical variable and coded using dummy variables, with risperidone (the most frequently prescribed medication) serving as the reference category.
DATA AVAILABILITY:
The anonymized data supporting this study are available in the public GitHub repository: https://github.com/Quncy0990/rTMS-OT-cohort
Access restricted. Please log in or start a trial to view this content.
Participant characteristics
There was no statistically significant difference in general data including age, gender, years of education, course of disease, and antipsychotic drugs between the two cohorts of patients (P > 0.05), as shown in Table 1. No dropped out patient during the 8-week treatment process were included in either cohort.
Psychotic symptoms (PANSS)
Before treatment, there were no significant di...
Access restricted. Please log in or start a trial to view this content.
Since antipsychotics have unsatisfying effects on improving cognitive dysfunction, different non-invasive and psychosocial interventions have been developed to improve symptom levels and functioning24. This retrospective study demonstrated that combining rTMS with OT significantly improves both psychotic symptoms and cognitive function in patients with schizophrenia, with superior outcomes observed after 8 weeks of intervention compared to 4 weeks. These findings suggest that integrating neurostim...
Access restricted. Please log in or start a trial to view this content.
The authors declare that there is no conflict of interest.
This work was supported by General Project of Science and Technology Plan of Jiangxi Provincial Health Commission (No. 202511187).
Access restricted. Please log in or start a trial to view this content.
| Name | Company | Catalog Number | Comments |
|---|---|---|---|
| Aripiprazole | SPH Zhongxi, Shanghai, China | H20041506 | / |
| Magnetic stimulator | Yiruide, Wuhan, China | MagTD40 | Equipped with a figure-of-eight coil |
| Olanzapine | Hansoh, Jiangsu, China | H20010799 | / |
| Paliperidone | Shijiazhuang Pharmaceutical Group Ouyi Pharmaceutical, Hebei, China | H20233701 | / |
| PANSS | / | / | Symptom assessment of schizophrenia patients |
| Quetiapine | Dongting Pharmaceutical, Hunan, China | H20061218 | / |
| R | R Foundation for Statistical Computing | R 4.4.1 | Statistical analysis |
| rBANS | / | / | Measure the cognitive function of schizophrenia patients |
| Risperidone | Huahai, Zhejiang, China | H20052330 | / |
| SPSS | IBM | SPSS 27.0 | Statistical analysis |
Access restricted. Please log in or start a trial to view this content.
Request permission to reuse the text or figures of this JoVE article
Request Permission