Materials and methods
To our knowledge, this is the first study to conduct a voxel-level investigation of the relationship between cerebellar GM and specific cognitive skills in a typically-developing pediatric population. The results support the coelenterazine that cerebellar posterior lobe GM is associated with cognitive performance, with evidence that specific regions are both generally implicated across multiple cognitive tasks, as well as specifically involved in particular domains. These findings are consistent with functional imaging studies reporting activation in the cerebellar posterior lobe for a range of cognitive measures (see Keren-Happuch et al., 2014; Stoodley and Schmahmann, 2009), and suggest that the functional topography described in adults is present in children and adolescents. Further, we established that the relationship between cerebellar GM and cognitive performance changes with age in specific cerebellar regions, with a continuous increase in the strength of the GM-cognition relationship as a function of age. Finally, it is important to note that these cerebellar results were identified in a whole-brain analysis, indicating that cerebellar GM is a robust predictor of cognitive performance in children and adolescents.
Data used in preparation of this article were obtained from the Pediatric Imaging, Neurocognition and Genetics Study (PING) database (http://ping.chd.ucsd.edu). As such, the investigators within PING contributed to the design and implementation of PING and/or provided data but did not participate in analysis or writing of this report. A complete listing of PING investigators can be found at https://ping-dataportal.ucsd.edu/sharing/Authors10222012.pdf. Data collection and sharing for this project was funded by the Pediatric Imaging, Neurocognition and Genetics Study (PING) (National Institutes of Health Grant RC2DA029475). PING is funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. PING data are disseminated by the PING Coordinating Center at the Center for Human Development, University of California, San Diego.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous deficits in social interaction and communication (APA, 2013). Social deficits in ASD are linked to abnormalities in the functioning of the amygdala, a limbic structure involved in processing salient, often emotionally charged, stimuli (Baron-Cohen et al., 1999; Critchley et al., 2000; Kleinhans et al., 2009; Monk et al., 2010; Weng et al., 2011). For example, Kleinhans et al. (2009) showed that lower rates of amygdala habituation to emotion are related to more severe social impairment based on social affect subscale scores from the Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000), and Swartz et al. (2013) found that lower habituation rates are related to greater impairment based on the Social Responsiveness Scale (SRS; Constantino et al., 2003), a more general measure of impairment (Hus et al., 2013). Early fMRI studies on amygdala functioning reported that ASD groups display reduced activation in this region relative to typically developing (TD) groups in response to emotional faces (Baron-Cohen et al., 1999; Critchley et al., 2000; Pierce et al., 2001), whereas more recent ASD studies found amygdala hyperarousal with a shorter stimulus presentation time (Monk et al., 2010; Weng et al., 2011; Kliemann et al., 2012). Such discrepant findings have warranted further investigation into the structures modulating amygdala activity.
The subgenual anterior cingulate cortex (sACC) has dense cortical connections to the amygdala, and is involved in amygdala inhibition (McDonald, 1998; Milad and Quirk, 2012; Ray and Zald, 2012), possibly through excitatory signaling to inhibitory regions of the amygdala (Rosenkranz and Grace, 2001). Connectivity between the sACC and the amygdala is implicated in the extinction of negative affect (Milad and Quirk, 2002; Maren and Quirk, 2004) and is linked to various mood disorders (Pezawas et al., 2005; Drevets et al., 2008).
Materials and methods