Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls

Abstract

Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal–striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition.

Effect of cocaine dependence on brain connections: clinical implications

“…All these effective connectivities had positive strength except for the connectivity from insula to medial frontal cortex. Consistent with the triple-system theory [7–8], these effective connectivity studies indicated that CD is associated with an imbalance among the PFC regions, insula, and striatal regions: weakened control of the PFC regions over the striatal regions during working memory [16] and response inhibition [17] and strengthened control of the striatal and insular regions over the PFC regions during the cocaine-Stroop task [18]. …”

“…Three effective connectivity studies were conducted to investigate neural correlates underlying working memory [16], response inhibition [17], and cue reactivity [18] in CDs. Ma et al [16] used dynamic causal modeling (DCM) of a working memory task and found that during short memory delay condition, the inferior frontal gyrus to striatum effective connectivity was reduced in CDs but increased in CTLs.…”

“…During the longer memory delay condition, the middle frontal gyrus to striatum effective connectivity was more reduced in CDs than in CTLs [14]. In another functional magnetic resonance imaging (fMRI) based DCM study, Ma et al [17] used a Go/NoGo task to test response inhibition in CDs and matched CTLs. Results of this study showed differences between groups in effective connectivity during the Hard NoGo condition: the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to left (L) caudate was increased in CTLs but remained the same in the CDs; the effective connectivity from R ventrolateral prefrontal cortex to L caudate was reduced in the CTLs but remained the same in the CDs; the effective connectivity from L anterior cingulate cortex (ACC) to L caudate remained the same in the CTLs but was reduced in the CDs.…”

Network failures: When incentives trigger impulsive responses

“…Assessing the SIB allowed us to investigate whether excessive premature responding and corresponding brain activations constitutes a vulnerability factor preceding drug use (Just et al, ). Given the importance of the striatum to top‐down control and reward processing in addiction and its abnormal neuronal connectivity with the PFC (Ma et al, 2014; Ma et al, ), we also investigated the selective involvement of this region and its effective connectivity using dynamic causal modeling (DCM) within key nodes of the PFC.…”

Effective Connectivity within the Mesocorticolimbic System during Resting-State in Cocaine Users

“…Using a stochastic dynamic causal modeling (DCM) approach, Ma et al (2014) showed that cocaine subjects differed from controls in that effective connectivity from inferior frontal cortex to striatum was less affected by an immediate working memory task in the cocaine compared to the control group, and the effective connectivity from middle frontal gyrus to the striatum was less affected by the delayed working memory task in the cocaine compared to the control group. And Ma et al (2015) utilized an fMRI-based stochastic DCM to study the effective neuronal connectivity associated with response inhibition in cocaine dependent subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The DCM analysis revealed that prefrontal-striatal connectivity was influenced during the NoGo conditions for both groups.…”