Striatal gating effect and prediction of treatment response in cocaine dependence

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e131 Methods: Pretreatment fMRI data during a working memory task were acquired from 6 CDs, who subsequently received DA enhancing medications at least 8 weeks, and 6 controls. Stochastic and nonlinear dynamic causal models (DCM) measured the effectively connectivity among 7 regions of interest: left (L) middle frontal gyrus (MFG), L inferior frontal cortex (IFC), L posterior parietal cortex (PPC), right (R) PPC, bilateral (LR) dorsal STR, LR ventral STR, LR thalamus. Two putative DCMs (a DCM in which MFG causally affects STR, and a DCM in which STR causally affects MFG) were tested. The activity in the dorsal STRwas hypothesized to gate (positive modulation effect) the connectivity from L IFC to L PPC, based on O’Reilly and Frank’s (2006) working memory model. Results: Results showed that MFG causally affected STR. The strength of the endogenous connectivity from MFG to ventral STR was lower in CDs than controls. Low pretreatment gating by the dorsal STR (possibly reflecting low pre-treatment DA function)was associatedwith improvement on theTreatment Effectiveness Score after treatment (r=−0.69). Conclusions: The lower strength of the MFG-ventral STR connectivity in CDs may reflect low DA function related to decreased prefrontal-striatal glutamatergic neurotransmission. The results are consistent with the theory that DA enhancement may be a useful target for pharmacotherapy of cocaine dependence in CDs who have pretreatment hypodopaminergic state. Financial support: Peter F. McManus Charitable Trust Grant (FGM & LM), NIDA Grants #P50 DA009262 & K02 DA00403 (FGM). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.372 Smoking-related psychopathology across cultures Michael Lyvers, C. Carlopio, M. Edwards Psychology, Bond University, Gold Coast, QLD,