Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease

The BDI-II is a 21-item self-reported questionnaire assessing the severity of depressive symptoms. Each item is scored from 0 to 3, yielding a total score ranging from 0 to 63, with higher scores indicating greater severity of depressive symptoms. Changes in BDI-II total score from baseline (T0) will be compared between the real rTMS and sham rTMS groups after treatment (T1) and at the follow-up assessment (T2).

The NPI is a caregiver- or informant-based assessment of neuropsychiatric symptoms. It evaluates 12 neuropsychiatric symptom domains based on symptom frequency and severity. Changes in NPI scores from baseline (T0) will be compared between the real rTMS and sham rTMS groups after treatment (T1) and at the follow-up assessment (T2).

Disease-specific questionnaire assessing quality of life in Parkinson's disease patients across 8 domains: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Scores range from 0 to 100; higher scores indicate worse quality of life.

Comprehensive clinician-administered scale assessing motor and non-motor symptoms of Parkinson's disease across 6 subscales: non-motor experiences of daily living, motor experiences of daily living, motor examination, motor complications, Hoehn and Yahr staging, and Schwab and England ADL scale. Higher scores indicate greater disease severity.

Self-reported scale assessing sleep disturbances in Parkinson's disease patients, consisting of 15 items rated on a 5-point Likert scale (0-4). Covers three domains: nocturnal motor symptoms, PD-specific nocturnal symptoms, and sleep-specific disturbances. Higher scores indicate more frequent sleep disturbances.

Korean validated version of the Toronto Alexithymia Scale consisting of 20 items rated on a 5-point Likert scale, assessing three factors: difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). Higher total scores indicate greater alexithymia.

Brief cognitive screening tool assessing multiple cognitive domains including attention, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Scores range from 0 to 30; higher scores indicate better cognitive function.

Automated facial expression analysis using FaceReader software to quantitatively assess facial action units (AUs) and emotional expression patterns. Participants perform facial emotion recognition and imitation tasks. Measures include response speed, latency, accuracy, and facial expression accuracy based on Action Unit analysis.

Quantitative assessment of eye movements using screen-based Tobii Pro Spark. Measures include gaze speed, gaze position, gaze duration, gaze latency, and pupil size during task performance, providing objective evaluation of oculomotor function.

Muscle activity is measured using DELSYS Trigno Avanti Sensor and Trigno Quattro Sensor attached to the skin with medical tape. Wireless measurement technology enables free movement during task performance, with real-time data collection via dedicated software.

Quantitative assessment of postural stability using BT4 balance evaluation system, measuring center of pressure (COP) displacement during standing. Assesses limits of stability in anterior, posterior, and lateral directions, and COP movement during Romberg test under eyes-open and eyes-closed conditions.

Basic physical information is collected using InBody580 with 4-pole 8-point tactile electrode method. Bioelectrical impedance is measured across 3 frequency bands (5kHz, 50kHz, 250kHz) in 5 body segments (right arm, left arm, trunk, right leg, left leg), yielding 15 impedance measurements.

Electrodermal activity is measured using the Shimmer Consensys GSR Development Kit, which records skin conductance changes between electrodes via wireless sensors. Sweat gland activation in response to internal or external stimuli alters skin moisture and ionic balance, producing measurable changes in electrodermal activity.

Neuroimaging assessment of brain structure using MRI with two sequences: T1-weighted and T2-weighted structural imaging. Used to evaluate structural changes before and after rTMS treatment, and to guide neuronavigation-based TMS targeting.

Quantitative measurement of candidate plasma biomarkers including Amyloid beta 40/42, Tau, phosphorylated Tau (p-Tau), and Neurofilament light chain (NfL) using antibody-based quantitative analysis methods (SIMOA, Luminex, or ELISA).

Safety will be assessed by the number and proportion of participants experiencing treatment-emergent adverse events (TEAEs) from the initiation of rTMS or sham stimulation through the final follow-up assessment. Adverse events will be summarized by event type, severity, and relationship to the investigational device. Serious adverse events, adverse device effects, and discontinuations due to adverse events will also be recorded and summarized by treatment group.