Cognitive Behavior Therapy for Irritability In High-Functioning ASD: Pilot Study of Neurobiological Mechanisms

Background:  In addition to the core symptoms, up to 50 percent of children with ASD exhibit irritability and disruptive behavior problems. If present in childhood, these problems may persist in adolescence and adulthood and place considerable strain on individuals and their families. Psychotropic medication, notably risperidone and aripiprazole, and psychosocial treatments based on applied behavioral analysis have been used for irritability in ASD.  There is also emerging evidence that Cognitive Behavioral Therapy (CBT) can be helpful for irritability in children with high-functioning ASD (Sofronoff et al., 2007).  CBT teaches children to recognize antecedents and consequences of problem behavior and to use emotion regulation and problem-solving skills to reduce irritability, aggression and noncompliance.

Objectives:  We investigated the neurobiological mechanisms of CBT by evaluating functional magnetic resonance imaging (fMRI) and electrophysiological (EEG) markers of socioemotional functioning before and after treatment in a 16-year old girl with Asperger Syndrome.

Methods: CBT was adapted from our work in typically developing children (Sukhodolsky et al., 2005, 2009) and consisted of 10 weekly sessions.  The ABC irritability subscale (Aman et al., 1985) was completed by the subject’s mother before and after treatment.  fMRI and EEG data were collected while the subject performed the frustration-induction Go-NoGo task before and after treatment.  The frustration-induction Go-NoGo task represents a mixed blocked/event-related design for fMRI and EEG studies.  The subject was asked to view a steady stream of objects and press the button in response to pre-determined experimental conditions. The opportunity to win a prize was manipulated across three conditions with known frustration-induction effects (Perlman and Pelphrey, 2010). We examined changes form pre- to post-treatment in 1) the fMRI blood oxygenation level dependent signal (BOLD) and 2) the amplitude of the Go versus NoGo N2 event related potentials (ERPs) between the neutral versus frustration conditions of the Go-NoGo task.

 Results:  Parent ratings revealed a decrease in the ABC irritability score from 17 at baseline to 5 at endpoint.  The fMRI regions of interest analysis revealed significantly increased activation from pre- to post-treatment in the subgenual anterior cingulate cortex, right ventrolateral prefrontal cortex, and left ventrolateral prefrontal cortex in frustration vs. neutral conditions.  The analysis of electrophysiological data revealed a reduction in the difference between NoGo and Go N2 ERPs at post-treatment versus pre-treatment in the frustration condition.

Conclusions:  The 12-point change in the ABC irritability score represents a meaningful decline in irritability which is similar to the mean improvement in the medication trials.  The fMRI results suggest that brain regions which are recruited in a cognitive task requiring emotion regulation following a period of frustration were hypoactive in the subject before treatment but showed increased activation following treatment with CBT for irritability.  The result of the ERP analysis suggests more efficient cognitive control of frustration when performing a response inhibition task after CBT.  Thus, reduction of irritability was paralleled by changes in the neural circuitry of emotion regulation. This pilot study supports the feasibility of using fMRI and EEG technology to investigate neurobiological mechanisms of CBT in adolescents with high-functioning ASD.