Transcranial direct current stimulation for compulsivity in adolescent fraternal twins with neurodevelopmental disorders

Compulsivity, a transdiagnostic symptom, is observed across multiple neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). Growing evidence suggests that diagnostic labels such as ASD, OCD, attention-deficit/hyperactivity disorder (ADHD), and anxiety do not have distinct etiologies and phenotypes, frequently co-existing [1]. Historically, research studies have recruited “clean” diagnostic samples which limits translational application in realworld clinical populations. Our goal was to design a symptomspecific, biobehavioral treatment strategy for youth experiencing compulsivity. Defined as feedback-insensitive, repetitive, habitual behaviors, compulsivity, is subserved by orbitofronto-striatal-thalamic neural circuitry. The right inferior frontal gyrus (rIFG) is a key node in this circuit, disrupting response tendencies by suppressing basal ganglia output to the motor cortex. Compulsivity has been associated with hypoactivity in this area [2]. With the aim of increasing activity in rIFG, we implemented our transcranial direct current stimulation (tDCS) montage (Fig. 1A) with anode placement over rIFG (FC6) and cathode over left orbitofrontal cortex (lOFC; Fp1). Neuromodulation was paired with computer-based cognitive training to augment behavioral outcomes [3]. With the approval of the IRB, we utilized a double-blind, between-subject, shamcontrolled design to investigate the impact of tDCS paired with cognitive training in 15-year old, female, fraternal adolescent twins. This design enabled us to capitalize on the reduced environmental, genetic, and developmental variance. Participants were diagnosed with ASD, ADHD, and anxiety. Both twins had parent-reported compulsive symptoms, and one had OCD as a comorbid diagnosis (P1). Each participant completed the following: (1) baseline assessments including parentcompleted surveyswithin oneweek of the first stimulation session; (2) five stimulation visits over seven days; and (3) postintervention assessments within 24 hours of the last stimulation session. We measured compulsivity using the Children’s YaleBrown Obsessive-Compulsive Scale (CY-BOCS), the ObsessiveCompulsive Inventory (OCI), and the Repetitive Behavior ScaleRevised (RBS-R). We also assessed hyperactivity-impulsivity using the ADHD Rating Scale-IV (ADHD-RS-IV). One twin (P1) received ten sessions of active (1mA) tDCS (StarStim 8, Neuroelectric; Barcelona, Spain) paired with cognitive training tasks (BrainHQ, Posit; San Francisco, USA) over one week, while the second twin (P2) was in the sham condition. Each study visit consisted of two 13min stimulation sessions separated by 20 minutes (Fig. 1B). P2 received a short ramp up of the current similar to the active condition followed by termination of the current in conjunctionwith the