The distinct functional brain network and its association with psychotic symptom severity in men with methamphetamine-associated psychosis

Abstract

Background: Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis.

Methods: We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity.

Results: The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN.

Conclusion: MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group.

Keywords: Brain; Functional magnetic resonance imaging (fMRI); Methamphetamine; Neurotransmitter; Psychosis.

Fig. 1

Flow diagram of study participants

Fig. 2

Significant group differences in large scale resting-state functional connectivity (rsFC) among the CRL, MNP, and MAP participant groups. Node color represents the network and corresponding distributions. a: Compared to the CRL group, the MNP subgroup shows enhanced rsFC between the FPN-DMN, SN-DMN, SMN-DMN, and SCN-DMN. b-c: The MAP group shows increased strength of rsFC between the SN-DMN and the SCN-DMN but decreased strength of rsFC between the SMN-DAN, SMN-VAN, SMN-SN, SMN-AN, and within SMN compared to the CRL group. d: Compared with the MNP subgroup, the MAP subgroup shows decreased strength of rsFC between the SMN-DMN, SMN-AN, SMN-FPN, DMN-VAN, and CON-AN. Abbreviations: CRL: healthy controls; MNP: methamphetamine users with no psychosis; MAP: methamphetamine-associated psychosis; DAN: dorsal attention network (red); VAN: ventral attention network (orange); SCN: subcortical network (maroon); SN: salience network (yellow); FPN: frontoparietal network (sea green); VN: visual network (lawn green); DMN: default mode network (dodger blue); AN: auditory network (slate grey); CON: cingulo-opercular network (deep pink); SMN: sensory/somatomotor network (dark violate); MN: memory network (grey)

Fig. 3

Relationships between and within the functional connectivity of the resting-state (rsFC) network and PANSS scores in the MAP and MNP subgroups. The PANSS-Total (PANSS-T), PANSS-Positive (PANSS-P), PANSS-Negative (PANSS-N), and PANSS-General Psychopathology (PANSS-GP) subscales were assessed, yielding a negative correlation with rsFC at corresponding sites. a: The PANSS-P is negatively correlated with the DMN-FPN and FPN-SMN. b: The PANSS-N is negatively correlated with the DMN-AN and within the SMN. c: The PANSS-GP is negatively correlated with the DAN-SN, SMN-CON, and SMN-SN. d: The PANSS-T is negatively correlated with the VN-FPN, AN-FPN, AN-SMN, SMN-CON, and within the SMN. Abbreviations: PANSS: Positive and Negative Syndrome Scale; DMN: default mode network (dodger blue); FPN: frontoparietal network (sea green); SMN: sensory/somatomotor network (dark violate); AN: auditory network (slate grey); DAN: dorsal attention network (red); SN: salience network (yellow); CON: cingulo-opercular network (deep pink); VN: visual network (lawn green)