Effects of taVNS Combined With tACS on Adolescents With Non-Suicidal Self-Injury

Official title

Effects of Combined taVNS and tACS on Adolescents With Non-Suicidal Self-Injury: A Randomized Controlled Trial

Overview

NSSI behavior is highly prevalent among adolescents, and its mechanisms are closely associated with attentional bias toward self-injury-related information and impulsivity, both of which may be related to reduced dlPFC activation levels. Introducing taVNS as a priming stimulus to pre-regulate brain state and optimize subsequent tACS treatment response provides a novel approach to addressing inconsistent intervention effects. Simultaneously, this facilitates a shift in the brain from passive stimulus reception to active state regulation, offering important theoretical foundations for developing more precise and efficient cross-modal neuromodulation therapies.This study aims to systematically validate the efficacy of a combined protocol using taVNS as a priming modality followed by tACS over the left dlPFC through a randomized controlled trial (RCT). The investigators hypothesize that: ① Compared to tACS intervention alone, this combined approach will not only demonstrate non-inferiority in overall therapeutic efficacy but, more importantly, significantly reduce inter-individual variability in treatment response to tACS. This would mitigate the issue of high clinical response heterogeneity and enhance the stability and predictability of treatment outcomes. ② Early behavioral biomarkers of intervention response are anticipated: Immediate improvements in attentional bias following a single combined intervention session will significantly predict reductions in the frequency and intensity of Non-Suicidal Self-Injury (NSSI) after a full course (14 sessions) of treatment. This suggests that early positive changes in cognitive function could serve as valid indicators predicting long-term clinical efficacy, offering a critical time window for implementing individualized treatment adjustments. ③ The study will elucidate the effects of the taVNS-primed combined tACS treatment on neuroimaging mechanisms in adolescents with NSSI.

Interventions

• Device 25Hz、300us transcutaneous auricular vagus nerve stimulation and10hz transcranial alternating current stimulation
  The active taVNS stimulation was applied to the cymba conchae, an area exclusively innervated by the auricular branch of the vagus nerve. Active taVNS stimulation protocol was set as follows: pulse width of 300 μs, frequency of 25 Hz, and current intensity adjusted based on each participant's individual threshold, set at 80% of the sensory threshold. The stimulation duration was 15 minutes. Active 10hz transcranial alternating current stimulation: 10 Hz tACS delivered through a 4×1-ring high-de
• Device sham 25Hz、300us transcutaneous auricular vagus nerve stimulation and 10hz transcranial alternating current stimulation
  The sham taVNS stimulation was placed on the earlobe. The two procedures were indistinguishable in terms of appearance, ensuring effective blinding. The stimulation duration was 15 minutes. Active 10HZ transcranial alternating current stimulation: 10 Hz tACS delivered through a 4×1-ring high-definition electrode montage centered on left DLPFC (F3), 2 mA peak-to-peak, 100 % intensity, gradually ramped up over 30 s, maintained for 20 min, then ramped down over 30 s; two sessions per day with at l
• Device active 25Hz、300us transcutaneous auricular vagus nerve stimulation and sham10hz transcranial alternating current stimulation
  The active taVNS stimulation was applied to the cymba conchae, an area exclusively innervated by the auricular branch of the vagus nerve. active taVNS stimulation protocol was set as follows: pulse width of 300 μs, frequency of 25 Hz, and current intensity adjusted based on each participant's individual threshold, set at 80% of the sensory threshold. The stimulation duration was 15 minutes. Sham 10HZ transcranial alternating current stimulation: identical 4×1-ring high-definition electrode mont

Primary outcome measures

• Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ) reduction in the frequency of self-injury [Time frame: Assessments were conducted at baseline (pre-treatment), as well as on day 1, at week 1, and at month 1 post-treatment.]
• Brief Barratt Impulsiveness Scale (BBIS) [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• Eye movement index-fixation counts [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• Stop Signal Task（SST） [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• Delay Discounting Task (DDT) [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]

Secondary outcome measures (7)

• Hamilton Depression Scale (HAMD-17) score [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• Hamilton Anxiety Scale (HAMA-14) score [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• the score of PANSI [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• The score of Ruminative Responses Scale (RRS) [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• The score of Difficulties in Emotion Regulation Scale-Short Form (DERS-16) [Time frame: Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.]
• The Patient Health Questionnaire-9 (PHQ-9) [Time frame: Assessments were conducted at baseline (pre-treatment), as well as on day 1, at week 1, and at month 1 post-treatment.]
• The Generalized Anxiety Disorder-7 (GAD-7) [Time frame: Assessments were conducted at baseline (pre-treatment), as well as on day 1, at week 1, and at month 1 post-treatment.]

Eligibility criteria

Inclusion criteria

• Meet the proposed diagnostic criteria for non-suicidal self-injury (NSSI) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with ≥5 documented self-injury episodes and at least one incident within the past month as assessed by the Adolescent Non-Suicidal Self-Injury Assessment Questionnaire (ANSAQ)
• Aged 12-18 years
• Right-handed
• Possess formal education experience sufficient to comprehend experimental protocols
• Normal or corrected-to-normal binocular visual acuity
• Voluntarily participate with legal guardians providing written informed consent

Exclusion criteria

• Montreal Cognitive Assessment (MoCA) score < 26
• History of suicide attempts
• History of epilepsy, brain surgery, tumors, or clinically significant head trauma
• History of substance abuse or severe physical diseases
• Received physical or psychological interventions within the past three months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• School of Mental Health and Psychological Sciences — Hefei

Identifiers

NCT: NCT07486804 · 81251050

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗