Parental substance abuse and function of the motivation and behavioral inhibition systems in drug-naïve youth

Abstract

It is hypothesized that the development of substance abuse (SA) may be due to imbalance in functions of the motivation-reward and behavioral inhibition systems in the brain. This speaks to the search for biological risk factors for SA in drug-naïve children who also exhibit motivational and inhibitory control deficits; however, this type of research is currently lacking. The objective of this study was to establish a neurobiological basis for addiction vulnerability using functional magnetic resonance imaging (fMRI) in drug-naïve youth with attention deficit/hyperactivity disorder (ADHD). We hypothesized that children with ADHD alone would show higher activity in regions of the motivation-reward and behavioral inhibition systems than children with ADHD and a parental history of SA. Toward this goal we scanned 20 drug-naïve children with ADHD ages 8-13 while performing an event-related reward task. High (N=10) and low (N=10) risk subjects were identified, based on parental history of SA. The effects of anticipation, conflict, and reward were assessed with appropriate linear contrasts, and between-group differences were assessed using statistical parametric mapping. The two groups did not differ on behavioral measures of the task. The fMRI results show heightened activation in the brain motivational-reward system and reduced activation of the inhibitory control system in high-risk compared to low-risk children. These results suggest that a functional mismatch between these two systems may represent one possible biological underpinning of SA risk, which is conferred by a parental history of addiction.

Figure 1. The Anticipation, Conflict, Reward (ACR) Task

Presented is the temporal relationship between the cue, flanker and outcome components of the ACR task. There is equal number of reward (n=64) and non-reward cues (n=64) as well as congruent (n=64) and incongruent (n=64) flankers that are randomly presented during the 4 sessions of the task. The outcome is performance-dependent: subjects must respond as quickly as possible by pushing a button (left or right) that corresponds to the direction of the central airplane. If the response is correct there is 50% chance of reward in the amount of $1; slow and/or incorrect responses result in $1 loss. A) Reward trial starts with a presentation of a Reward Cue followed by a Flanker and Reward Outcome that could be a $1 win OR $0 no-win OR -$1 loss; B) Non-Reward trial starts with a presentation of a Non-Reward Cue followed by a Flanker and Reward Outcome that could be a $0 no-win OR -$1 loss; The time duration of the components of the ACR task is presented at the bottom of the figure.

Figure 2. Activation during Anticipation (Reward Cue – Non-Reward Cue)

Presented in sagittal, coronal, and axial views are blood oxygenation level-dependent (BOLD) signal differences between the groups. BOLD signal in the left caudate, insula, orbito-frontal (OFC) and inferior frontal (IFC) cortices was higher in the high-risk than in the low-risk group. The figures were thresholded at p < .01 (one-tailed); the color bar indicates values of T.

Figure 3. Activation during Conflict (Incongruent – Congruent Flanker)

Presented in sagittal, coronal, and axial views are blood oxygenation level-dependent (BOLD) signal differences between the groups. BOLD signal in the right anterior cingulated cortex (ACC) and retrosplenial cingulate cortex (RCC) was higher in the low- risk than in the high-risk group. The figures were thresholded at p < .01 (one-tailed); the color bar indicates values of T.

Figure 4. Activation during Reward (Expected Reward – Expected Non-Reward)

Presented in sagittal, coronal, and axial views are blood oxygenation level-dependent (BOLD) signal differences between the groups. BOLD signal in the bilateral insula and the left orbitofrontal cortex (OFC) was higher in the high risk than the low risk group. The figures were thresholded at p < .01 (one-tailed); the color bar indicates values of T.

Figure 5. Activation during Punishment (Punishment – Expected Non-Reward)

Presented in sagittal, coronal, and axial views are blood oxygenation level-dependent (BOLD) signal differences between the groups. BOLD signal in the right insula cortex was higher in the high risk (HR) vs. low risk (LR) group. The figures were thresholded at p < .01 (one-tailed); the color bar indicates values of T.