Marjolein Luman

Identifying the neurobiology of altered reinforcement sensitivity in ADHD: A review and research agenda

ADHD is associated with altered reinforcement sensitivity, despite a number of inconsistent findings. This review focuses on the overlap and differences between seven neurobiologically valid models and lists 15 predictions assessing reinforcement sensitivity in ADHD. When comparing the models it becomes clear that there are great differences in the level of explanation. For example, some models try to explain a single core deficit in terms lower-level reinforcement systems, such as the dopamine transfer to reward back in time. Other models explain multiple deficits, by describing higher-level systems, such as impaired bottom-up prefrontal activation. When reviewing the available experimental evidence in support of the predictions, most experimental studies have been focusing on behavioral changes in the face of reward and response cost over no-reward, and on delay discounting. There is currently a lack in studies that focus on explaining underlying cognitive or neural mechanisms of altered reinforcement sensitivity in ADHD. Additionally, there is a lack in studies that try to understand what subgroup of children with ADHD shows alterations in reinforcement sensitivity. The scarcity in studies testing the neurobiological predictions is explained partly by a lack in knowledge how to test some of these predictions in humans. Nevertheless, we believe that these predictions can serve as a useful guide to the systematic evaluation of altered reinforcement sensitivity in ADHD.

Does neurocognitive functioning predict future or persistence of ADHD? A systematic review

Many children with ADHD remain symptomatic in (young) adulthood. It is important to understand what characterizes this persistent ADHD group. Since ADHD has been associated with neurocognitive dysfunctioning on a variety of neurocognitive domains, and many of these domains are influenced by the same risk genes that influence ADHD, neurocognitive functions are a potential predictor for ADHD persistence. We carried out a systematic literature review on the predictive value of neurocognitive functioning for future ADHD. Based on eighteen studies there was no evidence that either automatically controlled (requiring little mental effort; lower level), or more consciously controlled (requiring high levels of mental effort; higher level) neurocognitive functions differentiated ADHD persistence from remittance. In general, both persisters and remitters showed weaker performance than typically developing controls, although the effect was smaller for remitters. Neurocognitive functions measured in childhood predicted ADHD a few years later, regardless of the type of neurocognitive function. Our findings do not support the model of Halperin and Schulz (2006), which suggests a maturation of more consciously controlled neurocognitive functions in ADHD remitters.

ERPs associated with monitoring and evaluation of monetary reward and punishment in children with ADHD

BACKGROUND Several models of attention-deficit hyperactivity disorder (ADHD) propose abnormalities in the response to behavioural contingencies. Using event-related potentials (ERPs), the present study investigated the monitoring and subsequent evaluation of performance feedback resulting in either reward or punishment in children with ADHD (N = 18) and normal controls (N = 18) aged 8 to 12 years. METHODS Children performed a time production task, in which visual performance feedback was given after each response. To manipulate its motivational salience, feedback was coupled with monetary gains, losses or no incentives. RESULTS Performance feedback signalling omitted gains as well as omitted losses evoked a feedback-related negativity (FRN) in control children. The FRN, however, was entirely absent in children with ADHD in all conditions. Moreover, while losses elicited enhanced amplitudes of the late positive potential (LPP) in controls, omitted rewards had this effect in ADHD. CONCLUSIONS The lack of modulation of the FRN by contingencies in ADHD suggests deficient detection of environmental cues as a function of their motivational significance. LPP findings suggest diminished response to punishment, but oversensitivity to the loss of desired rewards. These findings suggest that children with ADHD have problems assigning relative motivational significance to outcomes of their actions.

Decision-making in ADHD: sensitive to frequency but blind to the magnitude of penalty?

BACKGROUND Decision-making and reinforcement sensitivity were investigated in 23 children with ADHD and 20 healthy controls using a gambling paradigm. METHODS Children were required to choose between three alternatives that carried (A) small rewards and small penalties (advantageous), (B) large rewards and increasing penalties and (C) small rewards and increasing penalties (both disadvantageous). Penalties increased either in frequency or magnitude in two independent conditions. Heart rate (HR) and skin conductance (SC) were measured to examine whether impaired decision-making was accompanied by autonomic abnormalities. RESULTS Children with ADHD showed a maladaptive response style compared to controls by demonstrating a smaller preference for the advantageous alternative, when penalties increased in magnitude. When penalties increased in frequency, children with ADHD performed like controls. Group differences in decision-making attenuated after the task was administered twice. Compared to controls, performance of children with ADHD in the magnitude condition was accompanied by increased HR acceleration following reward. In this condition, the post-selection SC of children with ADHD was larger for advantageous than for disadvantageous alternatives, in contrast to controls who showed an opposite SC pattern. CONCLUSIONS The current findings suggest that during decision-making, children with ADHD may be sensitive to the frequency but blind to the magnitude of penalty.

Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder.

BACKGROUND Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. AIMS To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD case-control study. METHOD At baseline we assessed ADHD, conduct disorder and oppositional defiant disorder. Substance use disorders, nicotine dependence and stimulant treatment were assessed retrospectively after a mean follow-up of 4.4 years, at a mean age of 16.4 years. RESULTS Stimulant treatment of ADHD was linked to a reduced risk for substance use disorders compared with no stimulant treatment, even after controlling for conduct disorder and oppositional defiant disorder (hazard ratio (HR) = 1.91, 95% CI 1.10-3.36), but not to nicotine dependence (HR = 1.12, 95% CI 0.45-2.96). Within the stimulant-treated group, a protective effect of age at first stimulant use on substance use disorder development was found, which diminished with age, and seemed to reverse around the age of 18. CONCLUSIONS Stimulant treatment appears to lower the risk of developing substance use disorders and does not have an impact on the development of nicotine dependence in adolescents with ADHD.

Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD. METHOD We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age. RESULTS Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt. CONCLUSION ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings.

Inhibition, Reinforcement Sensitivity and Temporal Information Processing in ADHD and ADHD+ODD: Evidence of a Separate Entity?

This study compared children with ADHD-only, ADHD+ODD and normal controls (age 8–12) on three key neurocognitive functions: response inhibition, reinforcement sensitivity, and temporal information processing. The goal was twofold: (a) to investigate neurocognitive impairments in children with ADHD-only and children with ADHD+ODD, and (b) to test whether ADHD+ODD is a more severe from of ADHD in terms of neurocognitive performance. In Experiment 1, inhibition abilities were measured using the Stop Task. In Experiment 2, reinforcement sensitivity and temporal information processing abilities were measured using a Timing Task with both a reward and penalty condition. Compared to controls, children with ADHD-only demonstrated impaired inhibitory control, showed more time underestimations, and showed performance deterioration in the face of reward and penalty. Children with ADHD+ODD performed in-between children with ADHD-only and controls in terms of inhibitory controls and the tendency to underestimate time, but were more impaired than controls and children with ADHD-only in terms of timing variability. In the face of reward and penalty children with ADHD+ODD improved their performance compared to a neutral condition, in contrast to children with ADHD-only. In the face of reward, the performance improvement in the ADHD+ODD group was disproportionally larger than that of controls. Taken together the findings suggest that, in terms of neurocognitive functioning, comorbid ADHD+ODD is a substantial different entity than ADHD-only.

Does reward frequency or magnitude drive reinforcement-learning in attention-deficit/hyperactivity disorder?

Children with attention-deficit/hyperactivity disorder (ADHD) show an impaired ability to use feedback in the context of learning. A stimulus-response learning task was used to investigate whether (1) children with ADHD displayed flatter learning curves, (2) reinforcement-learning in ADHD was sensitive to either reward frequency, magnitude, or both, and (3) altered sensitivity to reward was specific to ADHD or would co-occur in a group of children with autism spectrum disorder (ASD). Performance of 23 boys with ADHD was compared with that of 30 normal controls (NCs) and 21 boys with ASD, all aged 8-12. Rewards were delivered contingent on performance and varied both in frequency (low, high) and magnitude (small, large). The findings showed that, although learning rates were comparable across groups, both clinical groups committed more errors than NCs. In contrast to the NC boys, boys with ADHD were unaffected by frequency and magnitude of reward. The NC group and, to some extent, the ASD group showed improved performance, when rewards were delivered infrequently versus frequently. Children with ADHD as well as children with ASD displayed difficulties in stimulus-response coupling that were independent of motivational modulations. Possibly, these deficits are related to abnormal reinforcement expectancy.

Different Mechanisms of White Matter Abnormalities in Attention-Deficit/Hyperactivity Disorder: A Diffusion Tensor Imaging Study

OBJECTIVE Literature regarding white matter (WM) abnormalities in attention-deficit/hyperactivity disorder (ADHD) is sparse and inconsistent. In this article, we shed more light on WM microstructure in ADHD, its association with symptom count, and the familiality of WM abnormalities in ADHD. METHOD Diffusion tensor imaging (DTI) was performed in a large sample of individuals with ADHD (n = 170), their unaffected siblings (n = 80), and healthy controls (n = 107), aged 8 to 30 years. Extensive categorical as well as dimensional data regarding ADHD status and symptom count were collected. A whole-brain voxelwise approach was used to investigate associations between ADHD status and symptom count and WM microstructure, as measured by fractional anisotropy (FA) and mean diffusivity (MD). RESULTS Individuals with ADHD showed decreased FA and decreased MD in several widespread, non-overlapping brain regions. In contrast, higher ADHD symptom count was consistently associated with increased FA and decreased MD in the ADHD group. Unaffected siblings resembled individuals in the ADHD group with regard to decreased FA but had MD similar to that in healthy controls. Results were not confounded by socioeconomic status, the presence of comorbidities, or a history of medication use. CONCLUSIONS Our results indicate widespread disturbances in WM microstructure in ADHD, which seem to be driven by 2 different mechanisms. Decreased FA in ADHD may be due to a familial vulnerability to the disorder, whereas a second mechanism may drive the association between ADHD symptom count and both higher FA and lower MD. Such different mechanisms may play an important role in the inconsistencies found in the current literature.

Impaired Decision Making in Oppositional Defiant Disorder Related to Altered Psychophysiological Responses to Reinforcement

BACKGROUND When making decisions, children with oppositional defiant disorder (ODD) are thought to focus on reward and ignore penalty. This is suggested to be associated with a state of low psychophysiological arousal. METHODS This study investigates decision making in 18 children with oppositional defiant disorder and 24 typically developing control subjects. Children were required to choose between three alternatives that carried either frequent small rewards and occasional small penalties (advantageous), frequent large rewards and increasing penalties (seductive), or frequent small rewards and increasing penalties (disadvantageous). Penalties in the seductive and disadvantageous alternatives increased either in frequency or magnitude in two conditions. Heart rate (HR) and skin conductance responses to reinforcement were obtained. RESULTS In the magnitude condition, children with ODD showed an increased preference for the seductive alternative (carrying large rewards); this was not observed in the frequency condition. Children with ODD, compared with typically developing children, displayed greater HR reactivity to reward (more HR deceleration) and smaller HR reactivity to penalty. Correlation analyses showed that decreased HR responses to penalty were related to an increased preference for large rewards. No group differences were observed in skin conductance responses to reward or penalty. CONCLUSIONS The findings suggest that an increased preference for large rewards in children with ODD is related to a reduced cardiac reactivity to aversive stimuli. This confirms notions of impaired decision making and altered reinforcement sensitivity in children with ODD and adds to the literature linking altered autonomic control to antisocial behavior.