Hyperconnectivity of social brain networks in autism during action-intention judgment

Highlights

• This fMRI study examined action-intention judgment in individuals with autism.

• Three brain networks were examined: face processing, mentalizing, and mirroring.

• Autism group showed hyperconnectivity in connectivity of different hubs.

• Connectivity was found to be correlated with autism symptomology.

Abstract

Deficits in social communication in autism spectrum disorder (ASD) have been documented using neuroimaging techniques such as functional MRI over the past decade. More recently, functional connectivity MRI has revealed altered connectivity in face processing, mentalizing, and mirroring brain networks, networks involved in the social brain in ASD. However, to our knowledge, previous studies have not examined these three networks concurrently. The purpose of the current study was to investigate the functional connectivity of the face processing, mentalizing, and mirroring networks (within each network and across networks) in ASD during an action-intention task in which participants were asked to determine the means and intention of a model's actions. We examined: a) within-network connectivity of each network using an ROI-to-ROI analysis; b) connectivity of each network hub to the rest of the brain using a seed-to-voxel analysis; c) the between-network connectivity of each network hub using ROI-to-ROI analysis; and d) brain-behavior relationships by correlating autism symptoms with brain connectivity. Task-fMRI data were used from 21 participants with ASD and 20 typically developing participants. The ASD group consistently showed significantly greater connectivity between networks and between hub regions to the rest of the brain. Hyperconnectivity in ASD may entail more and widespread resource utilization for accomplishing action-intention judgment.

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a prevalence rate of 1 in 59 children (Centers for Control Disease, 2018), characterized by impairments in social communication and repetitive and restricted behaviors and interests (American Psychiatric Association, 2013). Among the most researched social communication deficits of ASD are reduced attention to faces (Schultz et al., 2000; Shic et al., 2014; Turner-Brown et al., 2013; Webb et al., 2017) and diminished ability to attribute mental states to others (S. Baron-Cohen, 1991; Castelli et al., 2002; Kana et al., 2009; Kana et al., 2015), also known as mentalizing or theory of mind. In a retrospective study looking at home videotapes of children's first year birthday parties, Osterling and Dawson (1994) found that children who were later diagnosed with ASD looked at others' faces significantly less compared to typically developing (TD) children. In an eye-tracking study, Jones and Klin (2013) demonstrated that children who went on to be diagnosed with ASD looked significantly more at the mouth than at the eye when viewing faces. Additionally, children with ASD are less successful in mentalizing tasks compared to their TD peers (S. Baron-Cohen et al., 1985; Peterson et al., 2005). Thus, emerging evidence from behavioral, eye-tracking, and retrospective data point to face processing and mentalizing to be a complex task for children and adults with ASD.

At the neural level, functional magnetic resonance imaging (fMRI) studies have provided functional differences between TD and ASD in several regions of the social brain found to be implicated in the social deficits of ASD. For example, studies have reported decreased activation in the fusiform face area (FFA), a hub region of the face processing (FP) network, in ASD compared to TD in response to faces (Patriquin et al., 2016; Pierce et al., 2001); while other studies have shown no group differences in FFA activation (Hadjikhani et al., 2004). Similarly, the temporal parietal junction (TPJ), a hub region of the mentalizing network, has also shown decreased (Kana et al., 2015; Lombardo et al., 2011; Patriquin et al., 2016) and increased activation (White et al., 2014) in ASD compared to TD during mentalizing tasks. Furthermore, another network implicated in mentalizing is the mirror neuron system (MNS) (Alcala-Lopez et al., 2018; Libero et al., 2014; Schulte-Ruther et al., 2011), which has been found to respond to action execution and action simulation (Marsh and Hamilton, 2011). Mirroring involves associating one's own actions with the actions of others, and consequently, mediates mentalizing (Libero et al., 2014). Hub regions of the MNS include the ventral premotor cortex (PMv), inferior frontal gyrus (IFG), and inferior parietal lobule (IPL) (Caspers et al., 2010). Previous studies have found increased activation of the MNS in ASD compared to TD (Martineau et al., 2010; Wadsworth et al., 2018), and decreased activation in ASD compared to TD (Dapretto et al., 2006; Wadsworth et al., 2017; Williams et al., 2006).

More recently, the literature has moved towards examining the functional connectivity (temporal correlation of activity among brain regions) (Whitfield-Gabrieli and Nieto-Castanon, 2012) of networks of brain regions rather than the activation of individual regions (Wass, 2011). Network neuroscience has shown that the social communication deficits observed in ASD may be the result of altered network functioning, rather than altered functioning of a single brain area (Mueller, 2007). Further, task-based functional connectivity provides the temporal correlation of activity among brain regions during a cognitive task (Just et al., 2004). Previous task-based functional connectivity studies have reported reduced connectivity of the FP network during tasks of face identification (Kleinhans et al., 2008) and face recognition (Koshino et al., 2008; Lynn et al., 2018) in ASD compared to TD. Likewise, the mentalizing network has been reported to show reduced connectivity during a task of mental state attribution of animated geometric figures (Kana et al., 2009, 2015) in ASD compared to TD. To-date, studies have not investigated task-based functional connectivity of the MNS in ASD compared to TD. However, during resting-state (i.e., in the absence of a cognitive task) functional connectivity, Fishman et al. (2014) found no differences in MNS connectivity between ASD and TD.

Fewer studies have also considered between-network connectivity and the connectivity of a hub (i.e., seed) region to the rest of the brain, as opposed to exclusively within-network connectivity. These first two approaches are needed to understand which level of the brain (i.e., within-network, between-network, and seed region to whole brain) social deficits in ASD may be stemming from. In sum, differences in activation of single brain regions and altered functional connectivity of social brain networks (FP, mentalizing, and mirroring) in ASD may be correlated with social deficits.

Neuroimaging studies in ASD, in general, have largely focused on examining a single network, such as FP or mentalizing, but rarely in combination. However, there seems to be a close relationship between FP, mentalizing, and mirroring, the three elements that may form the foundation of social cognition. Thus, the primary objective of this fMRI study is to examine the functional connectivity of three social brain networks (FP, mentalizing, and MNS networks) simultaneously during an active task of action understanding (Libero et al., 2014) involving implicit face processing and explicit mentalizing in high-functioning adults with ASD, in order to identify which level of the brain may show altered functional connectivity in ASD compared to TD. Adapted from de Lange et al. (2008), the task portrays a model interacting with common household objects (e.g., coffee cup, phone) in ordinary and unusual ways. There are two conditions, intentions and means, during the task. During the intention condition, participants are asked to determine whether the intention behind the model's actions is ordinary or unusual. In other words, participants are asked to attend to the model's mental state. Therefore, the mentalizing network is primarily involved during the intention condition. For example, during the intention-unusual condition, the model may hold a coffee cup in front of her eye. During the means condition, participants are asked to determine whether the way in which, or how, the model performed the action is ordinary or unusual. Due to its role in action-understanding, the MNS is involved during the means condition. For example, during the means-ordinary condition, the model may hold a coffee cup in front of her mouth. The FP network is involved in both intention and means tasks. Because the model's face is part of the stimuli, attention to the face (implicit or explicit) is necessary to determine the model's intentions and means for this study's task (Libero et al., 2014).

The first aim of our study is to examine the within-network connectivity of the FP, mentalizing, and MNS networks in ASD compared to TD. Based on the hypo-connectivity findings of autism, suggesting reduced connectivity in FP, mentalizing, and MNS networks (Just et al., 2012; Kana et al., 2009; Kleinhans et al., 2008), we hypothesized that the ASD group would show decreased connectivity within each network compared to the TD group during both intention and means conditions of the task. The second aim of this study is to examine the connectivity of the hub region of each network (FFA in FP network, TPJ in mentalizing network, and PMv in mirroring network) to the rest of the brain. For this aim, we hypothesized that the ASD group would show decreased connectivity between each network hub region to the rest of the brain during intention and means tasks, based on the long-range hypo-connectivity account of ASD (Belmonte et al., 2004; Just et al., 2004). Third, to examine the synchronization between these three networks, we analyzed the connectivity between each hub region (FFA-TPJ-PMv), and hypothesized the ASD group would show decreased connectivity during intention and means tasks (Just et al., 2012; Kana et al., 2009; Kleinhans et al., 2008). Lastly, to understand the relationship between ASD symptom severity and functional connectivity, we conducted exploratory correlations between participants’ scores on the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) (Ritvo et al., 2011) and the between-network connectivity of each hub region (FFA-TPJ-PMv).

To our knowledge, this is the first study to examine the functional connectivity of FP, mentalizing, and mirroring networks using a single task. Analyzing three components of social cognition in a task of action-intention judgment may be reflective of real-word social interactions, where multiple social and cognitive processes (perhaps mediated by FP, mirroring and mentalizing brain networks) are at play. Further, this study looks at within- and between-networks as well as uses ROI-to-ROI and seed-to-voxel techniques, providing different levels and scales of neural processing in ASD. Lastly, functional connectivity analyses allows for a more efficient approach at examining the synchronization of social information within and between networks. The implications of these findings may allow for a more comprehensive view of social cognition difficulties in ASD.