Reduced ventral medial prefrontal cortex (vmPFC) volume and impaired vmPFC-default mode network integration in codeine-containing cough syrups users

Drug Alcohol Depend. 2014 Jan 1;134:314-321. doi: 10.1016/j.drugalcdep.2013.10.023. Epub 2013 Nov 5.


Objective: To characterize the association between clinical symptoms and anatomical and functional cerebral deficits in codeine-containing cough syrups (CCS) users using voxel-based morphometry and resting state functional connectivity analysis.

Methods: Participants were 30 CCS users and 30 matched controls. Both groups were scanned using a volumetric three-dimensional fast field echo sequence and a gradient-echo echo-planar imaging sequence. Impulsivity traits of both groups were evaluated with the Barratt Impulsiveness Scale 11 (BIS 11). Voxel-based morphometry was used to characterize gray matter (GM) deficits in CCS users. The clinical significance of regional volume reduction was investigated by evaluating its association with impulsivity in CCS users and with alterations in resting state functional connectivity when brain regions with GM volume reduction were used as seed areas.

Results: Significantly decreased GM volume was observed in CCS users in bilateral ventral medial prefrontal cortex (vmPFC) which was related to greater impulsivity in CCS users. Significantly decreased integration was found in CCS users between the vmPFC and the default mode network. Also, significantly enhanced functional connectivity was found between the vmPFC and the right insula, and the right dorsal lateral PFC. Negative correlation was observed between BIS total scores, scores for attentional impulsivity and vmPFC-inferior parietal lobe connectivity in CCS users.

Conclusions: The findings revealed volume loss and aberrant functional organization in vmPFC among CCS users. In addition, the decreased vmPFC GM volume and attenuated functional connectivity of the vmPFC-inferior parietal lobe network were associated with clinical higher impulsivity trait in CCS users.

Keywords: Codeine-containing cough syrups; Cough medicine; Functional connectivity (FC); Ventral medial prefrontal cortex (vmPFC); Voxel-based morphometry (VBM).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Codeine / adverse effects*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Nerve Net / drug effects
  • Nerve Net / pathology*
  • Nerve Net / physiology
  • Nonprescription Drugs / adverse effects*
  • Organ Size
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / pathology*
  • Prefrontal Cortex / physiology
  • Prospective Studies
  • Substance-Related Disorders / diagnosis*
  • Substance-Related Disorders / physiopathology
  • Young Adult


  • Nonprescription Drugs
  • Codeine