Human anterior cingulate cortex (ACC) activity modulation has been observed in numerous tasks, consistent with a wide variety of functions. However, previous recordings have not had sufficient spatial resolution to determine whether microdomains (approximately one to two columns) are involved in multiple tasks, how activity is distributed across cortical layers, or indeed whether modulation reflected neuronal excitation, inhibition, or both. In this study, linear arrays of 24 microelectrodes were used to estimate population synaptic currents and neuronal firing in different layers of ACC during simple/choice reaction time, delayed word recognition, rhyming, auditory oddball, and cued conditional letter-discrimination tasks. Responses to all tasks, with differential responses to errors, familiarity, difficulty, and orienting, were recorded in single microdomains. The strongest responses occurred approximately 300-800 ms after stimulus onset and were usually a current source with inhibited firing, strongly suggesting active inhibition in superficial layers during the behavioral response period. This was usually followed by a sink from approximately 800 to 1400 ms, consistent with postresponse rebound activation. Transient phase locking of task-related theta activity in superficial cingulate layers suggested extended interactions with medial and lateral frontal and temporal sites. These data suggest that each anterior cingulate microdomain participates in a multilobar cortical network after behavioral responses in a variety of tasks.