Perioperative Low-Frequency rTMS for Sleep After Thoracoscopic Lung Resection

This is an investigator-initiated, single-center, prospective, randomized, double-blind, parallel-group, sham-controlled trial in adults undergoing elective thoracoscopic lung resection for primary lung cancer. Eligible participants will have evidence of preoperative sleep impairment, defined as an Insomnia Severity Index (ISI) score of at least 8 or a Richards-Campbell Sleep Questionnaire (RCSQ) score below 70 on the most recent evaluable preoperative inpatient night.

Participants will be randomized in a 1:1 ratio to active or sham stimulation. Active treatment will consist of 1-Hz repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex at the F3 position, delivered at 100% of the resting motor threshold with 1,800 pulses per session over approximately 30 minutes. Five sessions will be delivered within a 7-day perioperative window: on preoperative day 2, preoperative day 1, 2-6 hours after extubation when clinically stable, postoperative day 1, and postoperative day 2. No more than one study stimulation session will be delivered on the same calendar day, and study procedures will not delay surgery, necessary clinical care, or discharge.

The sham group will undergo matched stimulation using a dedicated sham coil or validated active/sham masking module. Target location, participant positioning, stimulation rhythm, sound, session duration, and study interaction procedures will be matched to active treatment, but the sham procedure will not provide the intended therapeutic cortical stimulation. Participants and outcome assessors will remain blinded to treatment allocation; stimulation operators cannot be blinded because of device-operation requirements but will not participate in recruitment, primary outcome assessment, data entry, or statistical analysis.

The primary outcome is the participant-level mean RCSQ total score across postoperative inpatient nights 1, 2, and 3. RCSQ scores range from 0 to 100, with higher scores indicating better sleep. The primary analysis will compare active and sham groups using ANCOVA/linear regression adjusted for the preoperative baseline RCSQ score and prespecified randomization stratification factors.

Secondary and exploratory outcomes include total sleep time measured using the Lifesense HR6 wearable device, sleep efficiency and other device-derived sleep measures when reliably available, postoperative pain, opioid consumption, rescue analgesia, quality of recovery, chest-tube duration, length of hospital stay, postoperative complications, longer-term sleep symptoms and chronic postsurgical pain, psychological symptoms, health-related quality of life, safety, and feasibility. Resting-state 64-channel EEG and a prespecified TMS-EEG mechanistic substudy will explore changes in spectral power, alpha peak frequency, functional connectivity, network topology, and TMS-evoked cortical responses.

Inclusion criteria

Age 18-80 years and able to understand the study and provide written informed consent.

Primary lung cancer diagnosed or suspected based on pathology and/or thoracic surgical multidisciplinary assessment, with planned elective thoracoscopic lung resection.

ASA physical status I-III, with expected awake extubation after surgery and ability to complete postoperative sleep and pain assessments.

Preoperative sleep impairment, defined as an Insomnia Severity Index (ISI) score ≥8 or a Richards-Campbell Sleep Questionnaire (RCSQ) score <70 on the most recent evaluable preoperative inpatient night.

Able to complete TMS safety screening, resting motor threshold assessment, RCSQ/ISI assessments, at least one baseline night of Lifesense HR6 monitoring, and 64-channel EEG.

The preoperative hospitalization schedule permits completion of two preoperative stimulation sessions, and postoperative hospitalization is expected to last at least three nights, allowing completion of the remaining three stimulation sessions without delaying surgery, necessary clinical care, or discharge.

Exclusion criteria

Unable to provide valid informed consent, unwilling to participate, or unable to reliably complete the primary RCSQ assessment.

History of epilepsy or unexplained seizures, active intracranial hemorrhage, significant cerebral edema, elevated intracranial pressure, recent stroke, or severe traumatic brain injury.

Intracranial ferromagnetic metal, cochlear implant, deep brain stimulator, cardiac pacemaker/implantable cardioverter-defibrillator, or other TMS-incompatible implant.

Severe scalp infection, open wound, or inability to safely position the TMS coil or EEG cap.

Pregnancy or any condition considered by the investigator to pose unacceptable risk.

Emergency surgery, planned open thoracotomy, or planned prolonged postoperative mechanical ventilation or deep sedation.

Chronic pain requiring regular preoperative opioid treatment, or pre-existing pain with an NRS score ≥3 in the target thoracic region.

Persistent delirium, respiratory distress, hemodynamic instability, active bleeding, or need for urgent reoperation after extubation.