Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

Abstract

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia.

The Role of Prefrontal Mixed Selectivity in Cognitive Control

“…3A,E). Moreover, at the population level, a decoding approach (Blackman et al, 2016, their Fig. 7A,B) showed that cue information gradually decayed during the delay period.…”

“…Second, instead of delay neurons, Blackman et al (2016) found many cueselective neurons that responded either in the cue or in the probe period. In B-cue trials, activity in these neurons increased when the cue was presented, whereas in A-cue trials, activity increased in the probe period.…”

“…Mixed neuronal selectivity has been proposed as an efficient way to expand the coding capabilities of neuronal populations (Stokes, 2011;Mante et al, 2013;Rigotti et al, 2013;Fusi et al, 2016). Neurons that respond to diverse combinations of task variables (including stimulus features, rules, and decisions) have been identified in the PFC (Warden and Miller, 2010;Stokes, 2011;Mante et al, 2013;Rigotti et al, 2013). The response patterns of these multitasking neurons change over the course of a trial and could enable cognitive flexibility.…”

“…In a paper published in The Journal of Neuroscience, Blackman et al (2016) recorded prefrontal single-cell activity while monkeys performed a task that demands cognitive control. The authors used a modified version of the AX continuousperformance task applied in clinical settings.…”

“…Subjects are instructed to respond whenever the letter X follows an A. In the dot pattern expectancy task (Blackman et al, 2016, their Fig. 1 A, C), letter stimuli are substituted with dot patterns (Jones et al, 2010) and the continuous nature of the task is replaced by a trial structure.…”