Hemispheric Asymmetry As an Electrophysiological Marker of Anxiety in Youth with Autism Spectrum Disorder

Background: Research suggests that a left-dominant pattern of hemispheric asymmetry (HA) in frontal cortical EEG activity is associated with generalized approach motivation, whereas a right-dominant pattern is related to withdrawal (Coan & Allen, 2004). Converging evidence suggests that right-dominant HA is evident in youth with autism spectrum disorder (ASD; Shamay-Tsoory et al., 2010). While resting frontal HA is also linked to emotion-related disturbances, such as anxiety (Tibodeau et al., 2006), it is not clear whether HA is related to anxiety in ASD, which are frequently comorbid (Simonoff et al., 2008). Recent findings indicate that frontal HA may predict internalizing symptom treatment response in typically-developing individuals (Baskaran et al., 2012) and may be malleable to a common ASD social skills intervention (SSI; Van Hecke et al., 2015); yet, it is not clear whether HA is a potential predictor of anxiety-related treatment response to SSIs.

Objectives: This study examined whether frontal HA in ASD is a correlate of co-occurring anxiety and a predictor of anxiety-related improvements in response to a SSI.

Methods: Thirty-nine youth (M_age=12.23, SD_age=2.99; 30 male) with IQ≥70 (M_IQ=105.74, SD_IQ=15.35) and ADOS-2-confirmed ASD diagnosis participated in a 10-week SSI. Pre- and post-test measures included self- and parent-report of psychopathology symptoms (BASC-2; Reynold & Kamphaus, 2004), self-report of social anxiety (SAS; La Greca & Lopez, 1998), and parent-report of psychiatric symptomatology, impairment (CASI-5; Gadow & Sprafkin, 2013), and anxiety symptomatology (MASC-2; March et al., 1997).

At baseline, resting EEG data were collected for 6 minutes alternating between 1-min blocks of eyes open or closed. Frontal alpha-band (8-12Hz) power was computed using a Fast Fourier transform with an 80-ms Hanning window and 50% overlap across segments, resulting in a 0.5Hz frequency resolution. Differences of natural log-transformed scores [Ln(Right) – Ln(Left)] were calculated for mean alpha power across F3(L)/F4(R) and F7(L)/F8(R) pairs, such that positive scores indicate greater relative left frontal brain activity (as alpha is inversely related to brain activity).

Results: Bivariate correlations revealed associations between greater left frontal brain activity and lower parent-reported anxiety symptomatology, including CASI-5 social anxiety symptom severity and impairment, multiple domains on the MASC-2 (including GAD, separation anxiety, social anxiety, and physical symptoms), and BASC-2 anxiety (see Table 1). Moreover, ANCOVA-of-change models revealed that greater left brain activity predicted greater reduction on self-reported BASC-2 anxiety marginally (β=-.299, p=.069) and SAS social anxiety (β=-.314, p=.014), particularly in social avoidance and distress in new situations (β=-.398, p=.003), over the course of the SSI.

Conclusions: Overall, our findings suggest that frontal HA is a useful marker of anxiety in youth with ASD, as evidenced across multiple measures of anxiety symptomatology. Importantly, individual differences in frontal HA predicted improvements in anxiety symptomatology following the SSI; this pattern was especially pronounced for social anxiety in new situations, which is consistent with the social approach model of HA (Lopez-Duran et al., 2012). These results suggest that frontal HA could be important for parsing the heterogeneity in comorbid anxiety in individuals with ASD, and predicting who may show the greatest anxiety-related response to treatment.