The Phase-Amplitude Coupling Induced by Drug Cues in Individuals With Methamphetamine Use Disorder During Withdrawal

Area of Science:

• Neuroscience
• Addiction Research
• Brain Connectivity

Background:

• Substance use disorder (SUD), particularly methamphetamine use disorder (MUD), presents a significant global health challenge.
• High addictiveness and relapse rates in MUD underscore the need to understand its neurophysiological underpinnings.
• The precise neural mechanisms driving MUD and cue-induced relapse remain largely unclear.

Purpose of the Study:

• To investigate multi-scale neural information integration in abstinent individuals with MUD.
• To examine cross-frequency coupling patterns in response to drug-related and neutral cues.
• To identify potential neural biomarkers for craving severity in MUD.

Main Methods:

• Electroencephalography (EEG) was recorded from 46 male abstinent individuals with MUD.
• Participants were exposed to both drug-related and neutral cues.
• Phase-amplitude coupling (PAC) and phase slope index (PSI) were employed to analyze local and directed neural connectivity.

Main Results:

• Cue-induced PAC changes correlated with craving severity: negative correlation in left prefrontal cortex (AF3) and positive correlation in centro-parietal regions (CP2).
• Phase slope index (PSI) analysis revealed altered information flow, including reversed prefrontal-to-occipital connectivity.
• Disrupted centro-parietal to sensorimotor network connectivity was observed under drug cue conditions.

Conclusions:

• Drug cues may intensify craving by impairing top-down prefrontal regulatory control and enhancing bottom-up sensorimotor pathways.
• PAC and PSI show promise as cue-reactive predictive biomarkers for assessing neural substrates of drug cue-induced craving in MUD.
• Understanding these neural dynamics is crucial for developing targeted interventions for MUD relapse prevention.