Disrupted prediction errors index social deficits in autism spectrum disorder

Abstract

Social deficits are a core symptom of autism spectrum disorder; however, the perturbed neural mechanisms underpinning these deficits remain unclear. It has been suggested that social prediction errors-coding discrepancies between the predicted and actual outcome of another's decisions-might play a crucial role in processing social information. While the gyral surface of the anterior cingulate cortex signalled social prediction errors in typically developing individuals, this crucial social signal was altered in individuals with autism spectrum disorder. Importantly, the degree to which social prediction error signalling was aberrant correlated with diagnostic measures of social deficits. Effective connectivity analyses further revealed that, in typically developing individuals but not in autism spectrum disorder, the magnitude of social prediction errors was driven by input from the ventromedial prefrontal cortex. These data provide a novel insight into the neural substrates underlying autism spectrum disorder social symptom severity, and further research into the gyral surface of the anterior cingulate cortex and ventromedial prefrontal cortex could provide more targeted therapies to help ameliorate social deficits in autism spectrum disorder.

Keywords: anterior cingulate cortex; autism spectrum disorder; social cognition; social prediction errors.

Figure 1

Task schematic and behavioural results. (A) A trial begins with the presentation of two white rectangles (doors) and the label of the Agent playing that trial. Once a door was chosen it changed colour indicating if the Agent has probably chosen the door with a prize (green) or the empty door (red). (B) The participant in the MRI scanner was shown the actual outcome before the other Agents. At this point the participant can determine if the outcome is expected (green-win/red-neutral) or unexpected (green-neutral/red-win). (C) The participant indicated if the outcome was expected (T) or unexpected (F) for all Agents and trials, after which the outcome is revealed to all Agents. Behavioural results showing accuracy [i.e. if participants correctly recognized that the outcome of the trial was expected (D) or unexpected (E)] shown for each Agent.

Figure 2

Group differences in social prediction error signalling. (A) Group × Belief × Agent interaction in the ACCg [Area 24 (78%; Neubert et al., 2015); MNI: 3 26 20, thresholded at P < 0.001 uncorrected] time-locked to the privileged information cue (Fig. 1B). (B) Per cent signal change values from the ACCg showing Agent specific prediction errors (prediction error − predictable outcome). first+, third+ and Cmp+ refer to positive outcome trials for first person, third person and Computer trials, respectively. first−, third− and Cmp− refer to negative outcome trials for first person, third person and Computer trials, respectively. This highlights that BOLD differences in the ACCg were driven by third person unexpected rewards (third prediction error positive) compared to all other trials. (C) Fitted responses from the ACCg for third person prediction error positive (blue) and third person predictable outcome positive (black) in TD subjects. (D) Fitted responses from the ACCg for third person prediction error positive (red) and third person predictable outcome positive (black) in ASD. This highlights that the third+ response in ASD in B was driven by larger responses to third predictable outcome positive trials rather than third prediction error positive trials (also see Supplementary Fig. 2). (E) Scatter plot showing the significant correlation (r = 0.66) between third person prediction error positive per cent signal change values and social symptom severity in ASD.

Figure 3

Group differences encoding Agency and connectivity with the ACCg. (A) Group × Agent interaction in vmPFC [Area 32PL (Neubert et al., 2015); MNI: 3 44 5, thresholded at P < 0.001 uncorrected] time-locked to privileged information (Fig. 1B). (B) Bar plots illustrating percent signal change [prediction error (PE) + predictable outcome] in vmPFC for TD and ASD. The activation in vmPFC was driven by an Agent effect in TD (first person > third person and Computer) that is not present in ASD. Error bars indicate standard error. (C) Bar plots illustrating that a boost in connectivity from the vmPFC to the ACCg specifically for third person (social) prediction errors in the TD group. (D and E) Correlations between effective connectivity strength social prediction errors in TD (D) and ASD (E). This shows a significant correlation between connectivity from the vmPFC to the ACCg and the strength of social prediction errors in TD (r = −0.46), which is absent in ASD (r = 0.15).