Figure 3.

Key Figure: A Gradient of Frontal Network Engagement as a Function of Sequencing Complexity

Sequence processing, similar to many behaviorally complex operations, is supported by an interacting network of brain areas. Increasing sequence complexity modulates the network and the involvement of particular regions in distinct ways, as illustrated. When predictions are relatively simple (e.g., adjacent relationships ​where one element directly predicts the next element in the sequence), they engage a network that includes the ventral frontal and opercular cortex (vFOC) in both humans and monkeys. In humans, when sequence relationships ​become more complex (either nonadjacent relationships ​or nested relationships, where several associations must be processed), the combinatorial codes required for integrating and mediating the respective dependencies involve interaction between regions of frontal cortex and other parts of the spatially distributed network, as illustrated. Presenting any given stimulus may elicit a distinct pattern of neuronal (unit) responses in sensory cortex (illustrated by the dot patterns). Through associative learning, these neuronal response patterns can become representationally more similar for elements that predictably co-occur across sequences ⁸⁵, ⁹⁰. This process can occur several times for multiple or nested associations, but would require interactions between more dorsal cortical areas, as illustrated, that together can mediate and reinstate the multiple associations available throughout the network (see the section ‘Ventrodorsal Gradient Model of Frontal Cortex Function for Sequencing Operations’ in the main text). The human brain has specialized, functionally and anatomically, to support abilities more complex than those of nonhuman animals, with language a salient example. Therefore, alongside evolutionarily conserved, functional homologies, important divergences are also likely to exist (see Outstanding Questions, main text). Some evidence for a divergence of mechanisms comes from studies showing that areas 44 and 45 have greater variability in sequence processing across species ⁹, ¹⁰.