Prefrontal cortex activity related to abstract response strategies.

Many monkeys adopt abstract response strategies as they learn to map visual symbols to responses by trial and error. According to the repeat-stay strategy, if a symbol repeats from a previous, successful trial, the monkeys should stay with their most recent response choice. According to the change-shift strategy, if the symbol changes, the monkeys should shift to a different choice. We recorded the activity of prefrontal cortex neurons while monkeys chose responses according to these two strategies. Many neurons had activity selective for the strategy used. In a subsequent block of trials, the monkeys learned fixed stimulus-response mappings with the same stimuli. Some neurons had activity selective for choosing responses based on fixed mappings, others for choosing based on abstract strategies. These findings indicate that the prefrontal cortex contributes to the implementation of the abstract response strategies that monkeys use during trial-and-error learning.

Representation of future and previous spatial goals by separate neural populations in prefrontal cortex.

The primate prefrontal cortex plays a central role in choosing goals, along with a wide variety of additional functions, including short-term memory. In the present study, we examined neuronal activity in the prefrontal cortex as monkeys used abstract response strategies to select one of three spatial goals, a selection that depended on their memory of the most recent previous goal. During each trial, the monkeys selected a future goal on the basis of events from the previous trial, including both the symbolic visual cue that had appeared on that trial and the previous goal that the monkeys had selected. When a symbolic visual cue repeated from the previous trial, the monkeys stayed with their previous goal as the next (future) goal; when the cue changed, the monkeys shifted from their previous goal to one of the two remaining locations as their future goal. We found that prefrontal neurons had activity that reflected either previous goals or future goals, but only rarely did individual cells reflect both. This finding suggests that essentially separate neural networks encode these two aspects of spatial information processing. A failure to distinguish previous and future goals could lead to two kinds of maladaptive behavior. First, wrongly representing an accomplished goal as still pending could cause perseveration or compulsive checking, two disorders commonly attributed to dysfunction of the prefrontal cortex. Second, mistaking a pending goal as already accomplished could cause the failures of omission that occur commonly in dementia.

Conditional motor learning in the nonspatial domain: effects of errorless learning and the contribution of the fornix to one-trial learning.

Conditional motor learning contributes importantly to behavioral flexibility. In previous work, the authors found that fornix transections impaired the ability of macaque monkeys (Macaca mulatta) to learn conditional motor associations between the nonspatial features of visual stimuli and nonspatially differentiated responses. In the present study, they found that significant 1-trial learning of such associations also depended on the fornix. Furthermore, removal of the hippocampus, subiculum, and subjacent parahippocampal cortex, added to fornix transection, had no effect, thus demonstrating that fornix transections eliminated the contribution of the hippocampal system. In addition, the authors examined the effect of errorless learning and found, in control monkeys, that errors made prior to the 1st correct response retarded 1-trial learning.

Comparison of population activity in the dorsal premotor cortex and putamen during the learning of arbitrary visuomotor mappings.

A previous study found that as monkeys learned novel mappings between visual cues and responses, neuronal activity patterns evolved at approximately the same time in both the dorsal premotor cortex (PMd) and the putamen. Here we report that, in both regions, the population activity for novel mappings came to resemble that for familiar ones as learning progressed. Both regions showed activity differences on trials with correct responses versus those with incorrect ones. In addition to these common features, we observed two noteworthy differences between PMd and putamen activity during learning. After a response choice had been made, but prior to feedback about the correctness of that choice (reward or nonreward), the putamen showed a sustained activity increase in activity, whereas PMd did not. Also in the putamen, this prereward activity was highly selective for the specific visuomotor mapping that had just been performed, and this selectivity was maintained until the time of the reward. After performance reached an asymptote, the degree of this selectivity decreased markedly to the level typical for familiar visuomotor mappings. These findings support the hypothesis that neurons in the striatum play a pivotal role in associative learning.

Comparison of learning-related neuronal activity in the dorsal premotor cortex and striatum.

Previous studies have reported learning-related changes in neuronal activity during conditional visuomotor learning, also known as arbitrary sensorimotor mapping, conditional visual discrimination, and symbolic or endogenous mapping. Qualitatively similar observations have been reported for the dorsal premotor cortex, the supplementary eye field, the prefrontal cortex, the hippocampus, the striatum and the globus pallidus. The fact that cells in both the dorsal premotor cortex (PMd) and the basal ganglia show changes in activity during associative learning enables a test of the hypothesis that cortex and basal ganglia function in distributed architectures known as cortical-basal ganglionic modules or 'loops'. We reasoned that if these loops represent functional entities, as proposed, then learning-related changes in activity should occur simultaneously in both the cortical and striatal nodes of a loop. The present results confirmed this prediction; as monkeys learned conditional visuomotor associations, neurons in the premotor cortex and associated parts of the putamen changed their rates at approximately the same time. For the largest number of neurons, the evolution in neural activity occurred in close correspondence to the monkeys' learning curves. As a population, however, learning-related changes in activity continued after the monkeys reached an asymptote in performance.

Fornix transection impairs conditional visuomotor learning in tasks involving nonspatially differentiated responses.

Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response.