Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro.

Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.

Feedback on Trait or Action Impacts on Caudate and Paracingulum Activity.

There is a general conception that positive associations to one's trait, e.g. 'I'm clever', are beneficial for cognitive performance. Scientific evidence shows that this is a simplification. In this functional magnetic resonance imaging (fMRI) study we used written trial-based trait feedback 'you are clever', or task feedback 'your choice was correct', on each correct response of a rule-switching task, to investigate how the character of positive self-associations influences performance outcome. Twenty participants took part in this crossover design study. We found that trait feedback was less beneficial for motivation and performance improvement, and resulting in enhanced neural activation on more difficult bivalent rule trials. This indicates that the task was treated as more complex in this condition. For example, 'you are clever' feedback led to enhanced activation in anterior caudate nucleus, an area known to process uncertainty. We further observed that activation in anterior paracingulate cortex was sensitive to whether self-reflection was imposed by external feedback or generated from internal processes, where the latter activation correlated positively with performance when following after task feedback. Our results illustrate how feedback can evoke self-reflections that either help or hinder motivation and performance, most likely by impacting on processes of uncertainty. The results support social psychological models stipulating that trait focus take resources away from task focus.

Impact of feedback on three phases of performance monitoring.

We investigated if certain phases of performance monitoring show differential sensitivity to external feedback and thus rely on distinct mechanisms. The phases of interest were: the error phase (FE), the phase of the correct response after errors (FEC), and the phase of correct responses following corrects (FCC). We tested accuracy and reaction time (RT) on 12 conditions of a continuous-choice-response task; the 2-back task. External feedback was either presented or not in FE and FEC, and delivered on 0%, 20%, or 100% of FCC trials. The FCC20 was matched to FE and FEC in the number of sounds received so that we could investigate when external feedback was most valuable to the participants. We found that external feedback led to a reduction in accuracy when presented on all the correct responses. Moreover, RT was significantly reduced for FCC100, which in turn correlated with the accuracy reduction. Interestingly, the correct response after an error was particularly sensitive to external feedback since accuracy was reduced when external feedback was presented during this phase but not for FCC20. Notably, error-monitoring was not influenced by feedback-type. The results are in line with models suggesting that the internal error-monitoring system is sufficient in cognitively demanding tasks where performance is ∼ 80%, as well as theories stipulating that external feedback directs attention away from the task. Our data highlight the first correct response after an error as particularly sensitive to external feedback, suggesting that important consolidation of response strategy takes place here.