Disambiguating Reward Circuitry Function In Autism: New Insight Into Social Cognition From a Three-Group fMRI Study

Background:

A number of theorists have suggested that autism is characterized by motivational deficits centered around appetitive pursuit of social activities     (Dawson et al., 2005; Schultz, 2005), ultimately leading to diminished interest in engaging in reciprocal social behaviors. Recent research from our group has highlighted disruptions in the dopamine-rich mesolimbic reward pathway as a potential explanation for this phenomenon (Dichter, Richey et al., under review). The mesolimbic pathway influences the perception of natural rewards such as food, sex and social interactions. Abnormal (upward) modulation of this circuit has been linked to pathologic pursuit of drugs of abuse, whereas under-recruitment leads to diminished pleasure from normally rewarding stimuli. Although it has been posited that social-motivational deficits in autism are perhaps mediated by this circuit, it is unknown whether dysfunction in the mesolimbic pathway is specific to autism, or whether it is a non-specific phenomenon shared by any disorder characterized by deficits in social-motivational behaviors.

Objectives:

  To address this issue, we conducted fMRI on a group of 16 adults with autism, 18 neurotypical control subjects, and a group of patients (N=15) with a psychiatric disorder that is also characterized by problems in social approach behavior: Social Anxiety Disorder (SAD).

Methods:

During fMRI, subjects completed a well-validated task of reward circuitry function, the monetary incentive delay task (M.I.D.; Knutson et al., 2002), which is designed to assess neural responses during both anticipatory and outcome phases of reward processing.  We assessed neural functioning in the nucleus accumbens and other nodes in the mesolimbic pathway while anticipating and receiving 1) social rewards (human faces) and 2) money rewards.

Results:

Using responses to money as a baseline for reward circuit functioning, we found that in comparison to controls, both autism and SAD subjects displayed significantly diminished activity in the nucleus accumbens during anticipation of faces (Right Accumbens; talairach x,y,z, 41,74,61; F[1,49]=6.68, p = .01; Left Accumbens; 61,74,60, F[1,49]=6.556, p = .012). However, autism was best differentiated from SAD on the basis of amygdala functioning. Specifically, we found that in comparison to SAD, autism subjects displayed greater amygdala activity during anticipation of faces, (Right Amgdala: talairach  34,60,66; F[1,29]=6.68, p = .01; Left Amygdala: talaraich: 58,60,64 F[1,29]=6.69, p = .01),  and relative to autism SAD displayed greater right amygdala firing during viewing of faces (Right Amygdala: F[1,29]=3.99, p < .05). In SAD, diminished responsivity in accumbens during face anticipation was associated with greater impairment in social reciprocity on the Social Responsiveness Scale (Constantino et al., 2003; r = .41; p<05). In autism increased responsivity in the amygdala during face anticipation was associated with greater impairment in social reciprocity (r = .39; p<05).

Conclusions:

Autism and SAD share common disruptions in the mesolimbic pathway, but autism may be differentiated from SAD by amygdala activity as a function of temporal phase (anticipation versus viewing of faces). The combination of low social-incentive motivation and high or even aversive anticipatory expectation (codified by the amgydala) could influence experience-dependent development such that nonsocial events acquire salience over social events.