An interventional study of temporal interference stimulation and Sham TIS in Schizophrenia Disorder and Cognitive Impairments, sponsored by Central South University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Central South University · Not applicable, Interventional, and Treatment
Prefrontal cortical dysfunction in patients with schizophrenia (SCZ) may result from impaired thalamic inputs to this region. Meanwhile, patients with SCZ exhibit a reduced GABA/glutamate ratio in the thalamus, indicating thalamic excitation/inhibition (E/I) imbalance. In addition, SCZ patients show marked reduction of sleep spindles, which are predominantly generated by the thalamic reticular nucleus. Therefore, thalamus-targeted temporal interference stimulation (TIS) may modulate the function of thalamocortical circuits, ameliorate clinical symptoms including cognitive deficits in patients with SCZ, and serve as an effective non-pharmacological intervention. This study consists of two trial components with three objectives: (1) to explore the therapeutic effect of TIS on cognitive function in patients with SCZ; (2) to explore the effect of TIS on positive symptoms in patients with SCZ; (3) to investigate the neural mechanisms underlying TIS-mediated symptom modulation in SCZ.
Trial 1: This study adopts a randomized, controlled, crossover design. Participants will be randomly assigned to two groups: Group A and Group B. Clinical data from 30 patients with schizophrenia (15 participants per group) will be collected, including baseline clinical rating scale scores, cognitive assessments, electroencephalography (EEG), and magnetic resonance imaging (MRI) data. All participants will receive two sessions of TIS intervention in a crossover fashion, with a 1-week washout period between the two interventions. One day prior to each TIS session, participants will complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects. Outcome measurements including clinical scale scores, cognitive assessments, EEG and MRI data will be acquired at baseline. Task-state MRI will be recorded during both stimulation sessions.
Trial 2: This trial uses a rigorous randomized controlled design. Participants will be randomized into two arms: the TIS group and the control group. Fifty patients with schizophrenia will be enrolled (25 participants per group). Baseline data will be collected, including clinical symptom ratings, cognitive function scores, EEG-derived E/I imbalance metrics, and MRI data. The intervention lasts for 2 weeks with twice-daily stimulation, totaling 20 sessions. Assessments will be performed at baseline, at the end of the 2-week intervention, and at a 4-week post-intervention follow-up to evaluate changes in clinical symptoms, cognition, EEG E/I imbalance, and brain structural and functional features. This trial aims to explore the short-term efficacy, safety, and neurobiological mechanisms of TIS for improving cognitive function in schizophrenia.
3,563 studies on the registry are indexed under Schizophrenia; 491 are open to participants now.
This study's planned enrollment of 80 is above the median of 71 across 2,944 interventional studies indexed under Schizophrenia.
Browse Schizophrenia studies →Central South University is the lead sponsor of 134 studies on the registry; 32 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
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A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Group A receives active stimulation in the first session and sham stimulation in the second session.One day prior to each TIS session, participants complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects.Electrodes are placed according to the 10-10 EEG system and secured with conductive paste.Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS.Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant.
Device: temporal interference stimulation · Device: Sham TIS
Group B receives sham stimulation in the first session and active stimulation in the second session.One day prior to each TIS session, participants complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects. Electrodes are placed according to the 10-10 EEG system and secured with conductive paste.Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS.Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant.
Device: temporal interference stimulation · Device: Sham TIS
Participants in the sham group receive sham TIS following the identical schedule: two sessions daily for 10 days, 20 sessions in total. The sham paradigm uses the same 2000 Hz current pair. Current is only delivered during the 10-second ramp-up and ramp-down phases at the start and end of each session, while no current is applied during the middle period. This setup mimics the scalp tingling sensation induced by current changes at the beginning and end of active stimulation. All other hardware, electrode placement and study procedures are identical to the active TIS group.
Device: Sham TIS
Participants in the TIS group receive active TIS stimulation, with two intervention sessions per day for 10 consecutive days, totaling 20 sessions. Each session lasts 30 minutes. Electrodes are placed according to the 10-10 EEG system and secured with conductive paste. Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS. Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant. Each stimulation session lasts 30 minutes, with a 10-second ramp-up period at the onset and a 10-second ramp-down period at the end.
Device: temporal interference stimulation
Thalamus-targeted temporal interference stimulation delivered via Dome Medical TES NEURO-800, individualized based on individual alpha frequency with electric field optimization from T1 MRI.
Sham temporal interference stimulation with identical setup; current only delivered during brief ramp-up/ramp-down periods to mimic scalp sensation without effective thalamic stimulation.
Changes in brain function
Functional MRI (fMRI) is based on the blood oxygen level dependent (BOLD) contrast that can detect changes in blood oxygenation to analyze the change of brain function after intervention.This outcome is for sub-trial 1 (single-session crossover TIS).
Time frame: baseline (T1 structural scan); pre-, during, and post-first stimulation (Day 1); pre-, during, and post-second stimulation (Day 9)
changes on the MATRICS Consensus Cognitive Battery (MCCB) scores
The MATRICS Consensus Cognitive Battery (MCCB) can be used for cognitive assessment of schizophrenia, bipolar disorder, and other neuropsychiatric diseases. The MCCB covers nine cognitive domains, including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function, and fine motor skills. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline,2 week visit, 4-week follow-up visit
Changes in Positive and Negative Symptom Scale-6 (PANSS-6) scores
The PANSS-6 is a shortened version of the Positive and Negative Syndrome Scale for assessment of psychotic symptoms in schizophrenia. Scores range from 6 to 42, higher score indicates more severe psychotic symptoms. This outcome is for sub-trial 1 (single-session crossover TIS).
Time frame: pre-and post-first stimulation (Day 1); pre- and post-second stimulation (Day 9)
Change in brain responses during the Sternberg Item-Recognition Paradigm (SIRP)
The Sternberg Item-Recognition Paradigm (SIRP) is a task fMRI paradigm for evaluating working memory processing. T1-weighted structural MRI at baseline is acquired for individual brain modeling. Task fMRI scans are obtained pre-stimulation, during stimulation, and post-stimulation for each session. This outcome is for sub-trial 1 (single-session crossover TIS).
Time frame: pre-, during, and post-first stimulation (Day 1); pre-, during, and post-second stimulation (Day 9)
Changes in brain function
Functional MRI (fMRI) is based on the blood oxygen level dependent (BOLD) contrast that can detect changes in blood oxygenation to analyze the change of brain function after intervention.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Change in PANSS total scores
The Positive and Negative Syndrome Scale (PANSS) is widely used to assess positive, negative and general psychopathology symptoms of schizophrenia. Scores range from 30 to 210, higher score indicates more severe positive and negative symptoms. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit
Change in PSYRATS scores
The Psychotic Symptoms Rating Scale (PSYRATS) quantifies the severity and dimensional features of hallucinations and delusions in patients with psychosis. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit
Change in SANS scores
The Scale for the Assessment of Negative Symptoms (SANS) evaluates the severity of negative symptoms in schizophrenia, including affective flattening, alogia, avolition-apathy, anhedonia-asociality and attentional impairment. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit
Change in GAF scores
The Global Assessment of Functioning (GAF) scale rates overall psychological, social and occupational functioning. Scores range from 0 to 100, higher score represents better functional status. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit
Change in Global Functioning Scale (GFS) scores
The Global Functioning Scale (GFS) assesses real-world social and role functioning among individuals with severe mental disorders. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in Social Functioning Scale (SFS) scores
The Social Functioning Scale (SFS) measures multiple domains of social functioning for patients with schizophrenia spectrum disorders. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline,4-week follow-up visit
Change in brain responses during the 2-back task fMRI paradigm
Task fMRI based on the 2-back working memory paradigm used to assess working memory-related thalamocortical brain activity. High-resolution T1-weighted structural MRI at baseline is acquired for individual brain modeling. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: 2-week visit (end of intervention)
Change in 1/f aperiodic EEG signal (E/I balance index)
The 1/f aperiodic signal of resting-state electroencephalography is measured as an index of excitation-inhibition (E/I) balance. This outcome is for sub-trial 2 (2-week repeated TIS).This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in long-range temporal correlation (LRTC) of resting EEG
Long-range temporal correlation (LRTC) of resting-state electroencephalography is measured as an index of excitation-inhibition (E/I) balance.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in functional E/I ratio (fE/I) of resting EEG
Functional E/I ratio (fE/I) from resting-state electroencephalography is measured as an index of excitation-inhibition (E/I) balance.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in gamma oscillatory power of resting EEG
Gamma-band oscillatory power of resting-state electroencephalography is measured as an index of excitation-inhibition (E/I) balance.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in beta oscillatory power of resting EEG
Beta-band oscillatory power of resting-state electroencephalography is measured as an index of excitation-inhibition (E/I) balance.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in 40 Hz auditory steady-state response (40 Hz-ASSR)
40 Hz auditory steady-state response (40 Hz-ASSR) is recorded by electroencephalography for excitation-inhibition balance assessment.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in mismatch negativity (MMN) amplitude
Mismatch negativity (MMN) is recorded by electroencephalography for excitation-inhibition balance assessment.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Change in P50 sensory gating ratio
P50 sensory gating ratio is recorded by electroencephalography for sensory gating assessment.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, after first stimulation,2-week visit (end of intervention), 4-week follow-up visit
Sleep spindle density from sleep EEG
Sleep spindle density is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Sleep spindle frequency from sleep EEG
Sleep spindle frequency is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Sleep spindle amplitude from sleep EEG
Sleep spindle amplitude is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Sleep spindle duration from sleep EEG
Sleep spindle duration is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Slow oscillation power from sleep EEG
Slow oscillation power is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Slow oscillation amplitude from sleep EEG
Slow oscillation amplitude is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Slow oscillation slope from sleep EEG
Slow oscillation slope is derived from sleep electroencephalography.This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 2-week visit (end of intervention)
Change in routine blood test parameters
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for routine blood examination. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in liver function parameters
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for liver function testing. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in renal function parameters
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for renal function testing. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in blood lipid levels
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for blood lipid testing. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in fasting plasma glucose concentration
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for fasting glucose testing. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
Change in peripheral inflammatory factor concentrations
Approximately 10 mL of intravenous blood is collected (2 mL whole blood, 4 mL serum, 4 mL plasma) at baseline and 4-week follow-up. Samples are sent to the clinical laboratory of the Second Xiangya Hospital, Central South University for inflammatory factor testing. Samples are destroyed immediately after testing, and test data are limited for use by the Second Xiangya Hospital, Central South University. This outcome is for sub-trial 2 (2-week repeated TIS).
Time frame: baseline, 4-week follow-up visit
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