Dorsolateral prefrontal cortex hyperactivity during inhibitory control in children with ADHD in the antisaccade task.

Children with ADHD show significant deficits in response inhibition. A leading hypothesis suggests prefrontal hypoactivation as a possible cause, though, there is conflicting evidence. We tested the hypoactivation hypothesis by analyzing the response inhibition process within the oculomotor system. Twenty-two children diagnosed with ADHD and twenty control (CTRL) children performed the antisaccade task while undergoing an fMRI study with concurrent eye tracking. This task included a preparatory stage that cued a prosaccade (toward a stimuli) or an antisaccade (away from a stimuli) without an actual presentation of a peripheral target. This allowed testing inhibitory control without the confounding activation from an actual response. The ADHD group showed longer reaction times and more antisaccade direction errors. While both groups showed activations in saccade network areas, the ADHD showed significant hyperactivation in the dorsolateral prefrontal cortex during the preparatory stage. No other areas in the saccade network had significant activation differences between groups. Further ADHD group analysis OFF and ON stimulant medication did not show drug-related activation differences. However, they showed a significant correlation between the difference in OFF/ON preparatory activation in the precuneus, and a decrease in the number of antisaccade errors. These results do not support the hypoactivity hypothesis as an inhibitory control deficit general explanation, but instead suggest less efficiency during the inhibitory period of the antisaccade task in children. Our findings contrast with previous results in ADHD adults showing decreased preparatory antisaccade activity, suggesting a significant age-dependent maturation effect associated to the inhibitory response in the oculomotor system.

Preparatory neural networks are impaired in adults with attention-deficit/hyperactivity disorder during the antisaccade task.

Adults with attention-deficit/hyperactivity disorder (ADHD) often display executive function impairments, particularly in inhibitory control. The antisaccade task, which measures inhibitory control, requires one to suppress an automatic prosaccade toward a salient visual stimulus and voluntarily make an antisaccade in the opposite direction. ADHD patients not only have longer saccadic reaction times, but also make more direction errors (i.e., a prosaccade was executed toward the stimulus) during antisaccade trials. These deficits may stem from pathology in several brain areas that are important for executive control. Using functional MRI with a rapid event-related design, adults with combined subtype of ADHD (coexistence of attention and hyperactivity problems), who abstained from taking stimulant medication 20 h prior to experiment onset, and age-match controls performed pro- and antisaccade trials that were interleaved with pro- and anti-catch trials (i.e., instruction was presented but no target appeared, requiring no response). This method allowed us to examine brain activation patterns when participants either prepared (during instruction) or executed (after target appearance) correct pro or antisaccades. Behaviorally, ADHD adults displayed several antisaccade deficits, including longer and more variable reaction times and more direction errors, but saccade metrics (i.e., duration, velocity, and amplitude) were normal. When preparing to execute an antisaccade, ADHD adults showed less activation in frontal, supplementary, and parietal eye fields, compared to controls. However, activation in these areas was normal in the ADHD group during the execution of a correct antisaccade. Interestingly, unlike controls, adults with ADHD produced greater activation than controls in dorsolateral prefrontal cortex during antisaccade execution, perhaps as part of compensatory mechanisms to optimize antisaccade production. Overall, these data suggest that the saccade deficits observed in adults with ADHD do not result from an inability to execute a correct antisaccade but rather the failure to properly prepare (i.e., form the appropriate task set) for the antisaccade trial. The data support the view that the executive impairments, including inhibitory control, in ADHD adults are related to poor response preparation.

The lateral hypothalamus and anterior hypothalamic nucleus differentially contribute to rats' defensive responses in the elevated plus-maze and shock-probe burying tests.

Lesions or pharmacological inhibition of the lateral septum reduce rats' open-arm avoidance in the elevated plus-maze and their burying behavior in the shock-probe test. The current study examined whether hypothalamic areas that receive direct input from the lateral septum also influence open-arm avoidance and defensive burying. Bilateral infusions of the GABA-A receptor agonist muscimol (20 ng) into the lateral hypothalamus selectively increased rats' open-arm avoidance without affecting shock-probe burying. In contrast, infusions of muscimol into the anterior hypothalamic nucleus suppressed burying without affecting rats' open-arm avoidance. These dissociations suggest that the lateral hypothalamus contributes to the exploration of potentially threatening environments, whereas the anterior hypothalamus influences defensive responses to proximal discrete threat stimuli.