Both the frontal cortex and the striatum send projections into the midbrain DA neurons, possibly underlying their ability to bootstrap to early predictors of reward. The loops may also explain another important aspect of goal-directed behavior: the sequencing of thought and action. A key feature of auto-associative networks is their ability

to learn temporal sequences of patterns and thus make predictions. This relies on the activity pattern being fed back into the network with a temporal lag, allowing the next pattern in the sequence to arrive as the previous pattern is fed back, building an association.32,33 Inhibitory synapses in the pathways through the BG may add the Inhibitors,research,lifescience,medical temporal delay needed, as they have a slower time

constant than excitatory synapses. Another way to add lag is via a memory buffer. As highlighted earlier, the PFC is well-known for this type of property; its neurons can sustain their activity to act as a Inhibitors,research,lifescience,medical bridge for learning contingencies across BX-795 mouse several seconds, even minutes. The introduction of lag into the recursive loop through either mechanism (or both) may be enough to allow sequencing and prediction. This would seem to be key to the development of tree-like rule representations Inhibitors,research,lifescience,medical that describe an entire sequence of goal-directed actions (discussed above). A brief word about capacity limitations Despite the remarkable power and flexibility of human cognition, our working memory—the “online” workspace that most cognitive mechanisms depend upon—is surprisingly limited. An average adult human has a capacity to retain only four items at a given time.34,36 Why this limited capacity? The

answer may lie in Inhibitors,research,lifescience,medical the mixed selectivity neurons that amplify the brain’s computational power (as previously discussed). Mixed selectivity neurons that participate in many different functions would seem to create problems. Don’t downstream neurons sometimes receive signals that are irrelevant or counterproductive? A solution is oscillatory brain rhythms. It has long been known that brain waves (coordinated oscillations among many neurons) Inhibitors,research,lifescience,medical vary their frequency with cognitive focus. Oscillations create synchronous spikes oxyclozanide that can have a greater impact than unsynchronized spikes, as they all arrive simultaneously at downstream neurons They could allow neurons to communicate different messages to different targets depending on those with which they are synchronized (and how, eg, phase, frequency). Evidence for this comes from a variety of studies. Different frequency synchronization between human cortical areas supports recollection of spatial vs temporal information.37 Different phases of cortical oscillations preferentially signal different pictures simultaneously held in short-term memory.38 Monkey frontal and parietal cortices synchronize more strongly at lower vs higher frequency for top-down vs bottom-up attention, respectively.