Send to

Choose Destination
Front Psychiatry. 2018 Mar 12;9:70. doi: 10.3389/fpsyt.2018.00070. eCollection 2018.

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

Author information

Department of Developmental Psychology, University of Amsterdam, Amsterdam, Netherlands.
Departement of Psychiatry, Academic Medical Centre, Amsterdam, Netherlands.
Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, Netherlands.
Departement of Radiology and Nuclear Medicine, Academic Medical Centre, Amsterdam, Netherlands.
Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Medical Centre, Nijmegen, Netherlands.


Background and aims:

Childhood 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.


In 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.


Neural 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.


Childhood 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.


amygdala; anxiety; childhood trauma; cocaine addiction; dorsal medial prefrontal cortex; functional connectivity; negative reinforcement; ventral striatum

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center