It seems conceivable that in the next 25 years, we will know enough about these mechanisms to begin to devise therapies to correct or ameliorate such dysfunction and possibly even reverse it. These therapies VX-770 solubility dmso will target circuits in ways we cannot imagine right now, because we lack the refined understanding of neural mechanism at the appropriate level. The findings reviewed in this essay afford insight into mechanisms at a systems and computational level. We might begin our steps toward refinement by listing three open questions about the decision process described in the beginning of this essay. (1) LIP neurons represent the integral of

evidence but we do not know how the integration occurs or whether LIP plays an essential role. (2) The coalescence of firing rate before Tin choices suggests that the mechanism for termination is a threshold or bound crossing, but we do not know where in the brain the comparison is made, how it is made, or how the bound is set. We think the bound is downstream of LIP, and when it is, integration stops, but we do not know how a threshold detection leads to a change in the state of the LIP circuit. We also do not know what starts the integration. There’s a reproducible starting time ∼200 ms after the onset of motion, but we do not know why this is so

long and what is taking place in the 100+ ms between the onset of relevant directional Adenylyl cyclase signals in

visual cortex and their representation in LIP. (3) We do not know how values are added to the integral of the evidence. selleck We’re fairly certain that time-dependent quantities, such as the urgency signal mentioned earlier or a dynamic bias signal (Hanks et al., 2011), are added, but we do not know whether they are represented independently of the DV and how they are incorporated into the DV. The answers to these questions will require the study of neural processing in other cortical and subcortical structures, including the thalamus, basal ganglia, and possibly the cerebellum. It makes little sense to say the decision takes place in area LIP, or any other area for that matter. Even for the part of the decision process with which LIP aligns—representation of a DV—it seems unlikely that the pieces of the computation arise de novo in LIP. Still, it will be important to determine which aspects of the circuitry play critical roles. Perhaps the most important problem to solve is the mechanism of integration. It is commonly assumed that this capacity is an extension of a simpler capacity of neurons to achieve a steady persistent activity for tenths of seconds to seconds (Wang, 2002), but this remains an open question. There are several elegant computational theories that would explain integration by balancing recurrent excitation with leaks and inhibition (Albantakis and Deco, 2009, Bogacz et al.