Enhanced Amygdala-Striatal Functional Connectivity during the Processing of Cocaine Cues in Male Cocaine Users with a History of Childhood Trauma

Abstract

Background and aimsChildhood trauma is associated with increased levels of anxiety later in life, an increased risk for the development of substance use disorders, and neurodevelopmental abnormalities in the amygdala and frontostriatal circuitry. The aim of this study was to investigate the (neurobiological) link among childhood trauma, state anxiety, and amygdala-frontostriatal activity in response to cocaine cues in regular cocaine users.MethodsIn this study, we included 59 non-treatment seeking regular cocaine users and 58 non-drug using controls. Blood oxygenation level-dependent responses were measured using functional magnetic resonance imaging while subjects performed a cue reactivity paradigm with cocaine and neutral cues. Psychophysiological interaction analyses were applied to assess functional connectivity between the amygdala and other regions in the brain. Self-report questionnaires were used to measure childhood trauma, state anxiety, drug use, drug use severity, and craving.ResultsNeural activation was increased during the presentation of cocaine cues, in a widespread network including the frontostriatal circuit and amygdala in cocaine users but not in controls. Functional coupling between the amygdala and medial prefrontal cortex was reduced in response to cocaine cues, in both cocaine users and controls, which was further diminished with increasing state anxiety. Importantly, amygdala-striatal connectivity was positively associated with childhood trauma in regular cocaine users, while there was a negative association in controls. At the behavioral level, state anxiety was positively associated with cocaine use severity and craving related to negative reinforcement.ConclusionChildhood trauma is associated with enhanced amygdala-striatal connectivity during cocaine cue reactivity in regular cocaine users, which may contribute to increased habit behavior and poorer cognitive control. While we cannot draw conclusions on causality, this study provides novel information on how childhood trauma may contribute to the development and persistence of cocaine use disorder.

Endophenotype Potential of Nucleus Accumbens Functional Connectivity: Effects of Polygenic Risk for Schizophrenia Interacting with Childhood Adversity

“…No main effect of CA was observed at the FCD or NAcc seed level which calls into attention that for mediation of some environmental factors, high genetic risk could be a prerequisite. We see a potential link between our result and epidemiological data that report previously trauma exposed children and adolescents [40], and amygdalastriatal FC changes were reported in male drug cocaine users with a history of CA [41]. In experimental animals, early life-adversity was identified as factor influencing GABAergic functions of the NAcc [70].…”

“…A relevant connection between early life stress and the mesocorticolimbic dopaminergic system has been detected using FC analysis of the VTA, identifying age-related attenuation of VTA/hippocampal connectivity [40]. Altered amygdala-striatal connectivity has been identified as a specific trait in male cocaine users with a history of CA [41], and impaired GABA signalling in the NAcc has been observed in animal models of early-life adversity [39].…”

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

“…In addition, stronger connectivity between the amygdala and limbic circuitry, including the striatum, is observed in patients with cocaine use disorder 43–44 . Finally, prior trauma in individuals with a cocaine use disorder has been found to enhance amygdala‐striatal connectivity both at resting state 45 and in response to cocaine cues 46 . An important focus of future studies will be to further dissect the specific neural circuitry driving cue‐ and chronic stress‐induced changes in cocaine seeking and relapse vulnerability.…”

How the harm of drugs and their availability affect brain reactions to drug cues: a meta-analysis of 64 neuroimaging activation studies

“…People with SUD show altered activity in early visual cortices when exposed to drug-related cues vs. neutral objects 17 , presumably mediating the attentional bias towards the substance. They also exhibit increased activity in regions involved in incentive motivational processes 18 , 19 of the mesocorticolimbic system 11 , 20 , 21 , in the ventral tegmental area (VTA) and its dopaminergic afferents to the ventral striatum, limbic structures (amygdala, hippocampus), and the prefrontal cortex (PFC). SUD is also associated with heightened responses in brain regions involved in the expression of habits 2 and in processing knowledge about tool use 22 , 23 , such as the dorsal-striatal circuits and the inferior temporal, parietal, and motor cortices.…”