Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-administered instrument used to assess the severity of depressive symptoms and sensitivity to treatment-related changes. The scale consists of 10 items with a total score ranging from 0 to 60. Higher scores indicate more severe depressive symptoms. The outcome will be calculated as the change in Montgomery-Åsberg Depression Rating Scale scores from baseline to each post-baseline assessment time point.

Incidence, type, and severity of adverse events related to the transcranial temporal interference stimulation, assessed using a standardized Neuromodulation Adverse Effects Questionnaire.

A 9-item self-report questionnaire used to assess depressive symptom severity. Total scores range from 0 to 27, with higher scores indicating greater depression severity. The outcome will be calculated as the change in PHQ-9 score from baseline to each post-baseline assessment time point.

Anxiety symptom severity will be assessed using the Hamilton Anxiety Rating Scale (HAMA), a 14-item clinician-administered scale with a total score range of 0 to 56. Higher scores indicate greater anxiety symptom severity, which represents a worse outcome. The outcome will be calculated as the change in HAMA total score from baseline to each post-baseline assessment time point.

The Young Mania Rating Scale (YMRS) is an 11-item clinician-administered instrument used to assess the severity of manic symptoms and to monitor treatment-emergent mania or hypomania. Total scores range from 0 to 60, with higher scores indicating more severe manic symptoms. The outcome will be calculated as the change in YMRS total score from baseline to each post-baseline assessment time point.

The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire used to assess subjective sleep quality and sleep disturbances over the previous month. The questionnaire generates a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality. The outcome will be calculated as the change in PSQI score from baseline to each post-baseline assessment time point.

The Beck Scale for Suicide Ideation (BSI) is a 19-item clinician-administered instrument used to assess the severity of suicidal thoughts, attitudes, and intentions. Total scores range from 0 to 38, with higher scores indicating more severe suicidal ideation. The outcome will be calculated as the change in BSI total score from baseline to each post-baseline assessment time point.

The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a 10-item self-report questionnaire used to assess psychological resilience and the ability to cope with adversity. Total scores range from 0 to 40, with higher scores indicating greater psychological resilience. The outcome will be calculated as the change in CD-RISC-10 total score from baseline to each post-baseline assessment time point.

The Chinese Version of the Cognitive Emotion Regulation Questionnaire (CERQ-C) is a 36-item self-report questionnaire used to assess cognitive emotion regulation strategies in response to stressful or negative life events. Total scores range from 36 to 180, with higher scores indicating greater use of cognitive emotion regulation strategies. The outcome will be calculated as the change in CERQ-C total score from baseline to each post-baseline assessment time point.

The State Anxiety Inventory (S-AI) is a 20-item self-report questionnaire used to assess transient anxiety experienced at the time of assessment. Total scores range from 20 to 80, with higher scores indicating greater state anxiety. The outcome will be calculated as the change in the S-AI total score from baseline to each post-baseline assessment time point.

A 7-item self-report questionnaire used to assess the severity of generalized anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater anxiety severity. The outcome will be calculated as the change in the GAD-7 total score from baseline to each post-baseline assessment time point.

The 17-item Hamilton Depression Rating Scale (HAMD-17) is a 17-item clinician-administered instrument used to assess the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating more severe depressive symptoms. The outcome will be calculated as the change in HAMD-17 total score from baseline to each post-baseline assessment time point.

The Sheehan Disability Scale (SDS) is a 3-item self-report questionnaire used to assess functional impairment in work/school, social life, and family life/home responsibilities. Total scores range from 0 to 30, with higher scores indicating greater functional impairment. The outcome will be calculated as the change in SDS total score from baseline to each post-baseline assessment time point.

The Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item self-report questionnaire used to assess anhedonia, or the ability to experience pleasure. Total scores range from 14 to 56, with higher scores indicating greater anhedonia (reduced ability to experience pleasure). The outcome will be calculated as the change in SHAPS total score from baseline to each post-baseline assessment time point.

The Ruminative Responses Scale (RRS) is a 22-item self-report questionnaire used to assess the tendency to engage in repetitive negative thinking in response to depressed mood or distress. Total scores range from 22 to 88, with higher scores indicating greater rumination. The outcome will be calculated as the change in RRS total score from baseline to each post-baseline assessment time point.

Brain structural and/or functional measures will be assessed using magnetic resonance imaging. The specific values and ranges depend on the imaging modality and derived measure, such as structural, functional connectivity, or brain network metrics. Interpretation will depend on the specific magnetic resonance imaging measure analyzed. The outcome will be calculated as the change in magnetic resonance imaging measures from baseline to each post-baseline assessment time point.

Brain electrophysiological activity will be assessed using electroencephalography (EEG). EEG-derived measures may include spectral power within predefined frequency bands, functional connectivity, synchronization, and other electrophysiological features. The specific values and ranges depend on the EEG-derived measure analyzed. Interpretation will depend on the specific EEG measure, with changes from baseline reflecting alterations in brain electrophysiological activity following the intervention. The outcome will be calculated as the change in EEG measures from baseline to each post-baseline assessment time point.

Peripheral blood samples will be collected for the assessment of blood-based biomarkers. The specific biomarkers, values, and reference ranges may vary depending on the laboratory assay and biological measure analyzed, such as inflammatory, metabolic, neuroendocrine, proteomic, metabolomic, transcriptomic, or other molecular profiles. Interpretation will depend on the specific biomarker assessed. The outcome will be calculated as the change in blood-based biomarkers from baseline to each post-baseline assessment time point.

Subjective anxiety and depression severity will be assessed using visual analogue scale ratings for anxiety and depression. Each visual analogue scale score ranges from 0 to 10, with higher scores indicating greater subjective symptom severity, which represents a worse outcome. The outcome will be calculated as the change in visual analogue scale scores from baseline to each post-baseline assessment time point.

Perceived stress will be assessed using the 10-item Perceived Stress Scale (PSS), a self-report questionnaire with a total score range of 0 to 40. Higher scores indicate greater perceived stress, which represents a worse outcome. The outcome will be calculated as the change in the PSS total score from baseline to each post-baseline assessment time point.

Cognitive function will be assessed using neurocognitive tests administered in this study. The score range depends on the specific cognitive test or task. For accuracy-based cognitive measures, higher scores indicate better cognitive performance, which represents a better outcome; for time-based measures such as reaction time, higher values indicate slower performance, which represents a worse outcome. The outcome will be calculated as the change in cognitive test performance from baseline to each post-baseline assessment time point.