Cingulate cortex: Diverging data from humans and monkeys

Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of distinguishing illusory cross-species differences from the true evolutionary differences that make our species unique.

Introduction

Effective action often requires choices between competing alternatives. In many cases, such competition is highly asymmetric and the decision is easy. However, in other cases, everyday behavior can give rise to conflict. An example of a task involving conflict is illustrated in Figure 1a. Extensive theoretical and computational modeling has suggested that monitoring for conflicts – in cases for which several mutually exclusive response options are simultaneously active – could signal the need for increased cognitive control 1, 2, 3. According to this influential view, activity in a conflict monitoring system can trigger adjustments in cognitive control to resolve current conflicts and prevent future ones [4] (Figure 1). Here we consider the neural basis of conflict monitoring, including several novel hypotheses that attempt to reconcile cross-species discrepancies revealed by recent studies of conflict monitoring in monkeys and humans.

It has been suggested that the human dorsal–caudal anterior cingulate cortex (ACC; also referred to as the anterior mid-cingulate cortex [5]; Figure 2a) acts as a conflict monitor 2, 3, 6 (for alternative views of ACC function see Refs 7, 8). Converging support for this hypothesis comes from functional MRI (fMRI) 9, 10, event-related potentials (ERP) [6], local field potentials (LFP) [11], single-unit activity (SUA) 12, 13, and lesion studies 14, 15 in humans. However, several recent studies have tested for conflict sensitivity in macaque monkey ACC using SUA recordings 16, 17, LFP recordings [18], and lesions [19] but found negative results. The conclusion often drawn from the animal research is that results from human studies have been misinterpreted 17, 20. However, a careful examination of the accumulated data reveals frank discrepancy rather than disconfirmation: data for monkeys seem to be simply incommensurable with the human data.

A series of examples reflect this point. For instance, Ito et al. found no conflict-related activity within monkey ACC using a saccade countermanding task (in which eye movement plans must be withheld just before execution) [16], whereas Curtis et al. [21] found conflict-related activity in single human subjects within ACC for the same task. Emeric et al. [18] observed a lack of conflict-related LFP in monkey ACC, whereas such activity has been detected in human ACC with ERP [6] and LFP [11]. Mansouri et al. [19] found no effect of monkey ACC lesions on behavioral reactions to conflict, whereas human ACC lesions are associated with changes in such reactions 14, 15. Ito et al. [16] and Nakamura et al. [17] found no conflict-related SUA in monkey ACC, whereas Davis et al. 12, 13 did find such SUA in human ACC.

What might explain these discrepancies? In what follows, we summarize what we consider to be the most plausible accounts available. For clarity, we organize these into two major categories. The first involves explanations relating to differences in the methods used to study monkeys and humans. The second looks to the perhaps neglected possibility that fundamental differences might exist between humans and monkeys at the level of functional neuroanatomy.