P2. Altered task switching as a marker for dysfunctional cortico-striatal pathways in ADHD

Introduction Impulsivity is one of the core symptoms of Attention-Deficit-Hyperactivity-Disorder (ADHD). However, the neural mechanisms underlying impulsivity remain poorly understood. Recent studies from our own lab have shown altered cortico-striatal functionality in healthy controls carrying long or short alleles of the NOS1ex1f-VNTR, a polymorphism associated with heightened impulsivity and ADHD. The study used a switching task to examine striatal functioning of the prefrontal cortex in those controls, which presumably is modulated by differential functionality of NOS1ex1f-VNTR, which in humans is mainly expressed in the striatum. The short allele of this polymorphism leads to a decrease in the expression of NO-Synthase. This switching task is known to be disturbed in Parkinson’s patients, a disorder affecting the striatum. Other studies also suggest a link between ADHD and altered cortico-striatal pathways, presuming that this dysfunctional cortico-striatal connection may be responsible for many of the symptoms of ADHD. Methods 19 patients with ADHD with no medication or a medication washout of at least 24 h and 20 healthy controls were given a set switching task. While performing that task, prefrontal brain activity was measured using near-infrared spectroscopy. Results Behavioral results showed a heightened error rate and reaction time for the ADHD group, as compared with the control group. However, this effect was not modulated by a varying difficulty for the switching tasks. Brain activation show a robust dorsolateral prefrontal activation pattern for the control group, switch trials activated the dorsolateral prefrontal cortex (dlPFC) more than the no-switch trials. ADHD subjects activated the dlPFC significantly less than did the control group, surprisingly, no modulation by the switching task could be found. Our hypothesis that the activation pattern of the ADHD group could hint at a dysfunctional mechanism in the fronto-striatal-frontal loop, hypothesized to be active in switching set, could not be validated. Whats more, an overall hypoactivation of the prefrontal cortex could be observed in patients with ADHD. Apparently their disease load is so high that patients were slower than controls even in the easy no switch condition. It is possible that the dysfunction in the striatum is so severe that patients overall prefrontal activation is suffering. However, with fNIRS it is not possible to disentangle the underlying mechanisms in subcortical areas, not even by means of measuring related prefrontal activity. Further studies using other imaging methods are needed to research the question of dysfunctional cortico-striatal loops in ADHD patients.