Individualized Neuromodulation for the Core Clinical Features of Drug Addiction

Individualized Neuromodulation Intervention Techniques for the Core Clinical Features of Drug Addiction

Using specific EEG biomarkers in methamphetamine-dependent individuals, this study systematically probes closed-loop tACS based on brain states, assessing dosage, neurologic and behavioral effects, while comparing its efficacy with traditional open-loop tACS methods.

Study Overview

• Status: Completed
• Conditions: Amphetamine Use Disorders
• Intervention / Treatment: Device: Closed-loop tACS stimulation based on addiction-induced states

Detailed Description

The current study delineates a robust correlation between prefrontal cortex EEG signals and the psychological craving associated with methamphetamine usage. Dependents exhibit heightened β oscillation energy in the MPFC region and diminished γ oscillation energy across the DLPFC-MPFC region. Previously, through the implementation of rTMS interventions on the left DLPFC, the investigators have successfully reduced the craving levels in users when exposed to relevant cues, coupled with observed decreases in β oscillation energy and increases in γ oscillation energy in the MPFC region. This indicates that both β and γ oscillation energies are instrumental in representing the involvement of MPFC and DLPFC during craving episodes, and neuromodulatory technologies can modulate these energy levels, consequently reducing cravings. Furthermore, the investigators identified a significant augmentation in the theta energy in the occipital lobe when MA dependents are confronted with drug-related cue imagery, signifying a potential crucial neural marker for addiction-induced brain activity. Therefore, the investigators intend to employ the non-invasive transcranial alternating current stimulation (tACS) technique, predicated upon biomarkers of addiction states, to administer specific frequency stimulations to targeted brain regions, aiming to achieve therapeutic objectives in addiction treatment.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals aged between 18 and 55 years, irrespective of gender, having completed a minimum of 9 years of education or capable of effectively cooperating in questionnaire and behavioral task evaluations.
• Meet the diagnostic criteria set forth by the DSM-5 concerning the severity of amphetamine-type substance addiction.
• A history of utilizing amphetamine-type substances for a duration not less than one year, with a frequency of use being at least once per week.
• Consent to actively cooperate in the completion of subsequent follow-up assessments.

Exclusion Criteria:

• Severe cognitive functional impairments manifested through a history of head trauma, cerebrovascular diseases, epilepsy, etc., or usage of cognitive enhancement drugs in the past 6 months; an intellectual disability with an IQ score less than 70.
• A diagnosis of schizophrenia or other severe mental illnesses as per the DSM-5 criteria.
• Abuse or dependence on other psychoactive substances (excluding nicotine) within the past 5 years.
• Severe organic diseases that might compromise study participation.
• Contraindications to tACS, such as a history of epileptic seizures or the presence of metallic implants in proximity to the head.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Closed-loop tACS stimulation based on addiction-induced states; Participants will receive closed-loop tACS interventions at different frequencies, with a 5-day interval between sessions. During each session, participants will be exposed to MA-related cue paradigms to induce cue-reactivity states, while scalp EEG signals are collected. Stimulation will be triggered only when specific EEG signals associated with MA cues are identified. The optimal frequency will be determined at the group level based on prespecified cue-reactivity EEG and inhibitory-control outcomes. Subsequently, participants will receive two additional control conditions at the identified optimal frequency: random-time stimulation, which will deliver the same number of stimulation events at pseudorandom time points independently of the EEG-defined brain state, and open-loop continuous stimulation, which will deliver an equivalent total stimulation dose continuously.

Device: Closed-loop tACS stimulation based on addiction-induced states; We will conduct a crossover study of closed-loop tACS interventions among participants with methamphetamine use disorder. Participants will receive three single-session EEG-triggered closed-loop tACS interventions at frequencies previously reported to improve cognitive control, administered in a counterbalanced within-subject order. After the optimal frequency is identified based on the predefined neurobehavioral outcomes, participants will receive two additional conditions at the same frequency: random-time stimulation and open-loop continuous stimulation. All five stimulation sessions will be separated by a 5-day interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stop-signal reaction time (SSRT) from the stop-signal task	The stop-signal task can indicate executive control capabilities by measuring Stop-signal reaction time. A shorter SSRT indicates better inhibitory functions.	Through study completion, an average of 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of electroencephalogram power spectrum	Resting-state EEG can be used to extract power spectra and electrode functional connectivity; on-task EEG can be used to isolate time-frequency features during non-stimulated trials to extract alpha, beta, theta, and gamma band energy of the parietal and occipital electrodes. Both can be used to assess changes in neural activity before, during, and after their restimulation.	Through study completion, an average of 1 month

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Study Chair: Min Zhao, PhD, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Actual): September 25, 2024
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: September 16, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 11, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 12, 2026
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: closed-loop; tACS; individualized therapy; Amphetamine-type stimulants
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: MZhao-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No