Aberrant functional connectivity of inhibitory control networks in children with autism spectrum disorder

Abstract

Development of inhibitory control is a core component of executive function processes and a key aspect of healthy development. Children with autism spectrum disorder (ASD) show impairments in performance on inhibitory control tasks. Nevertheless, the research on the neural correlates of these impairments is inconclusive. Here, we explore the integrity of inhibitory control networks in children with ASD and typically developing (TD) children using resting state functional Magnetic Resonance Imagaing (MRI). In a large multisite sample, we find evidence for significantly greater functional connectivity (FC) of the right inferior frontal junction (rIFJ) with the posterior cingulate gyrus, and left and right frontal poles in children with ASD compared with TD children. Additionally, TD children show greater FC of rIFJ with the superior parietal lobule (SPL) compared with children with ASD. Furthermore, although higher rIFJ‐SPL and rIFJ‐IPL FC was related to better inhibitory control behaviors in both ASD and TD children, rIFJ‐dACC FC was only associated with inhibitory control behaviors in TD children. These results provide preliminary evidence of differences in intrinsic functional networks supporting inhibitory control in children with ASD, and provide a basis for further exploration of the development of inhibitory control in children with the disorder. Autism Research 2018, 11: 1468–1478. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Inhibitory control is an important process in healthy cognitive development. Behavioral studies suggest that inhibitory control is impaired in autism spectrum disorder (ASD). However, research examining the neural correlates underlying inhibitory control differences in children with ASD is inconclusive. This study reveals differences in functional connectivity of brain networks important for inhibitory control in children with ASD compared with typically developing children. Furthermore, it relates brain network differences to parent‐reported inhibitory control behaviors in children with ASD. These findings provide support for the hypothesis that differences in brain connectivity may underlie observable behavioral deficits in inhibitory control in children with the disorder.

Frontoparietal Network in Executive Functioning in Autism Spectrum Disorder

“…The ALE analysis of the ASD group found seven significant clusters of activation in the following regions: left middle frontal gyrus (MFG) (BA 6), bilateral anterior insula (BA 13), LIFG (BA, BA 9), right precentral gyrus (BA 9), right inferior parietal lobule (RIPL) (BA 39, 40). Based on the ALE output, the left MFG cluster was contributed to by foci from four studies [Gilbert et al, 2008; Just et al, 2007; Koshino et al, 2008; Shafritz et al, 2015], the bilateral anterior insula cluster was contributed to by foci from four studies [Gilbert et al, 2008; Just et al, 2007; Shafritz et al, 2015; Yerys et al, 2015], the left IFG cluster was contributed to by foci from five studies [Agam et al, 2010; Gilbert et al, 2008; Just et al, 2007; Shafritz et al, 2015; Voorhies et al, 2018], the right precentral gyrus cluster was contributed to by foci from two studies [Koshino et al, 2008; Voorhies et al, 2018], and the RIPL cluster was contributed to by foci from two studies [Gilbert et al, 2008; Schmitz et al, 2006] (Fig. 2).…”

“…The ALE analysis of the TD group found 14 significant clusters of activation in the following regions: left superior frontal gyrus (SFG) (BA 6), right claustrum (BA 13), DLPFC (BA 9), primary visual cortex (BA 17), left precentral gyrus (BA 6), right inferior parietal lobe (BA 39), right frontal cingulate gyrus (BA 32), right MFG (BA 6), left insula (BA 13), left cingulate gyrus (BA 31), left putamen (−26, 4, −14), and gray matter activation (−34, 52, 12). Based on the ALE output, the left SFG cluster was contributed to by foci from six studies [Just et al, 2007; Koshino et al, 2008; Schmitz et al, 2006; Shafritz et al, 2015; Solomon et al, 2009; Voorhies et al, 2018], the right claustrum cluster was contributed to by foci from five studies [Gilbert et al, 2008; Just et al, 2007; Shafritz et al, 2015; Vogan et al, 2014, 2018], the DLPFC cluster was contributed to by foci from four studies [Gilbert et al, 2008; Shafritz et al, 2015; Vogan et al, 2014; Yerys et al, 2015], the primary visual cortex cluster was contributed to by foci from four studies [Schmitz et al, 2006; Solomon et al, 2009; Vogan et al, 2014, 2018], the left precentral gyrus cluster was contributed to by foci from four studies [Koshino et al, 2008; Solomon et al, 2009; Vogan et al, 2018; Voorhies et al, 2018], the right inferior parietal lobe cluster was contributed to by foci from three studies [Dichter & Belger, 2008; Koshino et al, 2008; Shafritz et al, 2015], the right frontal cingulate gyrus was contributed to by foci from four studies [Shafritz et al, 2015; Solomon et al, 2009; Vogan et al, 2014, 2018], the right MFG cluster was contributed to by foci from three studies [Gilbert et al, 2008; Schmitz et al, 2006; Shafritz et al, 2015], the left insula cluster was contributed to by foci from two studies [Gilbert et al, 2008; Shafritz et al, 2015], the left cingulate gyrus was contributed to by foci from two studies [Dichter & Belger, 2008; Duerden et al, 2012], the left putamen cluster was contributed to by foci from two studies [Koshino et al, 2008; Shafritz et al, 2015], and the gray matter activation cluster was contributed ...…”

“…Conversely, the ASD group showed greater activation relative to TD participants in the left anterior cingulate cortex (ACC) (BA 32), left cingulate gyrus (BA 31), and gray matter volume (48, 22, 16). Based on the ALE output, the left ACC cluster was contributed to by foci from two studies [Gilbert et al, 2008; Shafritz et al, 2015], the left cingulate gyrus cluster was contributed to by foci from one study [Voorhies et al, 2018], and the gray matter volume cluster was contributed to by foci from two studies [Duerden et al, 2012; Yerys et al, 2015] (Fig. 3 and Table 4).…”

“…When compared to TD, the ASD participants showed significantly decreased activation in the bilateral IPL (BA 40), left MFG (BA 6, 9), right precuneus (BA 7), left putamen (−24, 10, −16), left thalamus (−4, −20, 12), left medial prefrontal cortex (MPFC) (BA 8), and right superior parietal lobule (SPL) (BA 7). Based on the ALE output, the bilateral IPL cluster was contributed to by foci from four studies [Kana et al, 2007;Solomon et al, 2009;Vogan et al, 2018;Voorhies et al, 2018], the left MFG cluster was contributed to by foci from three studies [ Koshino et al, 2008;Solomon et al, 2009;Vogan et al, 2018], the right precuneus cluster was contributed to by foci from three studies Solomon et al, 2009;Vogan et al, 2014], the left putamen cluster was contributed to by foci from two studies [Koshino et al, 2008;Shafritz et al, 2015], the left thalamus cluster was contributed to by foci from two studies [Koshino et al, 2008;Solomon et al, 2009], the left MPFC cluster was contributed to by foci from two studies [Koshino et al, 2008;Vogan et al, 2014], the right SPL cluster was contributed to by foci from two studies [Solomon et al, 2009;Voorhies et al, 2018]. Conversely, the ASD group showed greater activation relative to TD participants in the left anterior cingulate cortex (ACC) (BA 32), left cingulate gyrus (BA 31), and gray matter volume (48,22,16).…”

“…At the neurobiological level, atypical brain responses while performing EF tasks are extensively documented in individuals with ASD [Braden et al, 2017; Garic, Broce, Graziano, Mattfeld, & Dick, 2019; Hanaie et al, 2018; Just, Cherkassky, Keller, Kana, & Minshew, 2007; Voorhies et al, 2018; Walsh, Baxter, Smith, & Braden, 2019]. Although studies examining brain structural abnormalities in ASD are limited, those to date report cortical and subcortical differences [Kemper & Bauman, 2002; Romero‐Garcia, Warrier, Bullmore, Baron‐Cohen, & Bethlehem, 2019; Van Rooij et al, 2018], delayed maturation of the frontal lobes [Zilbovicius et al, 1995], and structural abnormalities, including differences in the orbitofrontal cortex [Salmond, De Haan, Friston, Gadian, & Vargha‐Khadem, 2013], corpus callosum [Frazier & Hardan, 2009; Keary et al, 2009], prefrontal cortex (PFC) [Gilbert, Bird, Brindley, Frith, & Burgess, 2008; Rinaldi, Perrodin, & Markram, 2008] and in total brain volume [Freitag et al, 2009; Turner, Greenspan, & van Erp, 2016].…”