Neural mechanisms of belief inference during cooperative games.

Humans have the arguably unique ability to understand the mental representations of others. For success in both competitive and cooperative interactions, however, this ability must be extended to include representations of others' belief about our intentions, their model about our belief about their intentions, and so on. We developed a "stag hunt" game in which human subjects interacted with a computerized agent using different degrees of sophistication (recursive inferences) and applied an ecologically valid computational model of dynamic belief inference. We show that rostral medial prefrontal (paracingulate) cortex, a brain region consistently identified in psychological tasks requiring mentalizing, has a specific role in encoding the uncertainty of inference about the other's strategy. In contrast, dorsolateral prefrontal cortex encodes the depth of recursion of the strategy being used, an index of executive sophistication. These findings reveal putative computational representations within prefrontal cortex regions, supporting the maintenance of cooperation in complex social decision making.

Blocking central opiate function modulates hedonic impact and anterior cingulate response to rewards and losses.

Reward processing is linked to specific neuromodulatory systems with a dopaminergic contribution to reward learning and motivational drive being well established. Neuromodulatory influences on hedonic responses to actual receipt of reward, or punishment, referred to as experienced utility are less well characterized, although a link to the endogenous opioid system is suggested. Here, in a combined functional magnetic resonance imaging-psychopharmacological investigation, we used naloxone to block central opioid function while subjects performed a gambling task associated with rewards and losses of different magnitudes, in which the mean expected value was always zero. A graded influence of naloxone on reward outcome was evident in an attenuation of pleasure ratings for larger reward outcomes, an effect mirrored in attenuation of brain activity to increasing reward magnitude in rostral anterior cingulate cortex. A more striking effect was seen for losses such that under naloxone all levels of negative outcome were rated as more unpleasant. This hedonic effect was associated with enhanced activity in anterior insula and caudal anterior cingulate cortex, areas implicated in aversive processing. Our data indicate that a central opioid system contributes to both reward and loss processing in humans and directly modulates the hedonic experience of outcomes.

Empathy for pain involves the affective but not sensory components of pain.

Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one--present in the same room--was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AI and ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AI and rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.