Orbitofrontal Signaling of Future Reward is Associated with Hyperactivity in Attention-Deficit/Hyperactivity Disorder.

Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADHD), one of the most common psychiatric disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but the link between OFC dysfunction and behavioral deficits in ADHD, particularly in adolescence, remains poorly understood. Here we used advanced high-resolution functional magnetic resonance imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing (TD) controls (N = 39, age 12-16, all male except for one female per group) to study reward-related OFC responses and how they relate to behavioral dysfunction in ADHD. During fMRI data acquisition, participants performed a simple decision-making task, allowing us to image expectation-related responses to small and large monetary outcomes. Across all participants, we observed significant signal increases to large versus small expected rewards in the OFC. These responses were significantly enhanced in ADHD relative to TD participants. Moreover, stronger reward-related activity was correlated with individual differences in hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability was associated with normalized OFC responses. These results provide evidence for the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting the role of OFC-dependent goal-directed control mechanisms in this disorder.SIGNIFICANCE STATEMENT Attention-deficit/hyperactivity disorder (ADHD) is characterized by alterations in motivated behavior which can be understood as diminished goal-directed control. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but its potential contribution to ADHD symptomatology remains poorly understood. Using high-resolution fMRI, we show that adolescent ADHD patients display enhanced OFC signaling of future rewards and that these increased reward-related responses are correlated with the severity of hyperactivity/impulsivity. These findings suggest that an inability to adequately evaluate future outcomes may translate into maladaptive behavior in ADHD patients. They also challenge the idea that dysfunctions in dopaminergic brain areas are the sole contributor to reward-related symptoms in ADHD and point to a central contribution of goal-directed control circuits in hyperactivity.

Modulation of pre-attentive spectro-temporal feature processing in the human auditory system by HD-tDCS.

The present study examined the functional lateralization of the human auditory cortex (AC) for pre-attentive spectro-temporal feature processing. By using high-definition transcranial direct current stimulation (HD-tDCS), we systematically modulated neuronal activity of the bilateral AC. We assessed the influence of anodal and cathodal HD-tDCS delivered over the left or right AC on auditory mismatch negativity (MMN) in response to temporal as well as spectral deviants in 12 healthy subjects. The results showed that MMN to temporal deviants was significantly enhanced by anodal HD-tDCS applied over the left AC only. Our data indicate a left hemispheric dominance for the pre-attentive processing of low-level temporal information.

Comparison between conventional and HD-tDCS of the right inferior frontal gyrus in children and adolescents with ADHD.

OBJECTIVE: To investigate whether the effects of HD-tDCS and conventional tDCS of the right IFG are superior to the effects of sham stimulation for the improvement of working memory performance in ADHD. METHODS: 15 ADHD patients between 10 and 16 years underwent three tDCS sessions in which conventional, HD and sham tDCS of the right IFG were applied. In all sessions a 2-back working memory task was solved and EEG was recorded. Baseline data were assessed from 15 age matched healthy controls. RESULTS: In ADHD patients, increased positive values of P300 and N200 mean amplitudes were found after conventional and HD-tDCS. Thus, both components were more in resemblance to ERPs in healthy controls. Behavioral performance was not generally influenced by tDCS but effects of HD-tDCS depended on individual hyperactive/impulsive symptom load. The rate of responders for HD-tDCS was equivalent to the responder rate for conventional tDCS. CONCLUSIONS: ERP data indicate that HD-tDCS is equally suitable as conventional tDCS for the recruitment of the right IFG in the context of working memory processing. SIGNIFICANCE: HD-tDCS of the right IFG is a promising approach for neuromodulation in ADHD but further research is necessary to develop adaptations that produce reliable behavioral benefits.

Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS.

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance.

Improving Interference Control in ADHD Patients with Transcranial Direct Current Stimulation (tDCS).

The use of transcranial direct current stimulation (tDCS) in patients with attention deficit hyperactivity disorder (ADHD) has been suggested as a promising alternative to psychopharmacological treatment approaches due to its local and network effects on brain activation. In the current study, we investigated the impact of tDCS over the right inferior frontal gyrus (rIFG) on interference control in 21 male adolescents with ADHD and 21 age matched healthy controls aged 13-17 years, who underwent three separate sessions of tDCS (anodal, cathodal, and sham) while completing a Flanker task. Even though anodal stimulation appeared to diminish commission errors in the ADHD group, the overall analysis revealed no significant effect of tDCS. Since participants showed a considerable learning effect from the first to the second session, performance in the first session was separately analyzed. ADHD patients receiving sham stimulation in the first session showed impaired interference control compared to healthy control participants whereas ADHD patients who were exposed to anodal stimulation, showed comparable performance levels (commission errors, reaction time variability) to the control group. These results suggest that anodal tDCS of the right inferior frontal gyrus could improve interference control in patients with ADHD.