Gray's neuropsychological model of consciousness uses a hierarchical feedback loop framework that has been extensively discussed by many others in psychology. This commentary therefore urges Gray to integrate with, or at least acknowledge previous models. It also points out flaws in his feedback model and suggests directions for further theoretical work.

Because of their evolutionary importance, threat-detection mechanisms are likely to exist at a variety of levels. A recent study of face recognition suggests that novel stimuli receive enhanced processing when presented as fear-related. This suggests the existence of a complex, context-dependent threat-detection mechanism that can adaptively respond to spatiotemporally varying and unique environmental features.

Recoverin is a Ca2+-binding protein found primarily in vertebrate photoreceptors. The proposed physiological function of recoverin is based on the finding that recoverin inhibits light-stimulated phosphorylation of rhodopsin. Recoverin interacts with rod outer segment membranes in a Ca2+-dependent manner. This interaction requires N-terminal acylation of recoverin. Four types of fatty acids have been detected on the N-terminus of recoverin, but the functional significance of this heterogeneous acylation is not yet clear.

Transcendence, defined as the capacity to perceive the immediate stimulus environment in relation to long-range or abstract concerns, is a key aspect of self-control, and indeed self-regulation often breaks down because attention becomes focused exclusively on the immediate stimuli (i.e., transcendence fails). Factors that restrict attention to the here and now will weaken self-control, whereas factors that promote transcendence will enhance it. Guilt may be one example of the latter.

Gray hypothesizes that the contents of consciousness correspond to the outputs of a subicular (hippocampal/temporal lobe) comparator that compares the current state of the organism's perceptual world with a predicted state. I argue that Gray has identified a key contributing system to conscious awareness, but that his model is inadequate for explaining how conscious contents are generated in the brain. An alternative model is offered.

Rachlin argues that according to “teleological” behaviorism self-control is evident in instances where an act is contrasted with an element of a temporally extended behavioral pattern. A strength of the argument is that it incorporates an important role for temporally extended context in identifying self-control. Weaknesses of this viewpoint are that it de-emphasizes the identification of manipulable controlling variables in defining and accounting for the origins of patterns.

A review of data concerning the uneven distribution of phobias suggests that nonassociative, ethological models can account for most of tile important findings that cannot be attributed to expectancy biases. The origin of a variety of fears that appear in fixed developmental patterns across divergent cultures and species can best be explained by biological models.

The regulatory properties of the neurospecific, type I adenylyl cyclase and its distribution within brain have suggested that this enzyme may be important for neuroplasticity. To address this issue, the murine, Ca2+ -stimulated adenylyl cyclase (type I), was inactivated by targeted mutagenesis. Ca2+ -stimulated adenylyl cyclase activity was reduced 40% to 60% in the hippocampus, neocortex, and cerebellum. Long term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maxim um extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform normally in the Morris water task, they did not display a preference for the region where the platform had been when it was removed. The behavioral phenotype of these mice is very similar to that exhibited by mice which have been surgically lesioned in the hippocampus. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in spatial memory and indicate that the cAMP signal transduction pathway may play an important role for synaptic plasticity.

Rachlin's hyperbolic-discounting model captures basic features of the subtlety of human impulsiveness and self-control and has received convincing experimental support. His distinction between self-control patterns and impulsive acts expands his earlier work to a greater range of self-control behaviors. Possible mechanisms that may weaken or strengthen patterns of self-control are considered.

Recent studies from several different laboratories have provided further insight into structure-function relationships of cyclic nucleotide-gated channel and in particular the cCMPgated channel of rod photoreceptors. Site-directed mutagenesis and rod-olfactory chimeria constructs have defined important amino acids and peptide segments of the channel that are important in ion blockage, ligand specificity, and gating properties. Molecular cloning studies have indicated that cyclic nucleotide-gated channels consist of two subunits that are required to reproduce the properties of the native channels. Biochemical analysis of the cGMP-gated channel of rodcells have indicated that the 240 kDa protein that co-purifies with the 63 kDa channel subunit contains both the previously cloned second subunit of the channel and a glutamic acid-rich protein. The regulatory properties of the cGMP-gated channel from rod cells has also been studied in more detail. Studies indicate that the beta subunit of the cGMP-gated channel of rod cells contains the binding site for calmodulin. Interaction of calmodulin with the channel alters the apparent affinity of the channel for cGMP in all in vitro systems that have been studied. The significance of these recent studies are discussed in relation to the commentaries on the target article.

If sensations were behaviorally conceived, as they should be, as complex functional patterns of interaction between overt behavior and the environment, there would be no point in searching for them as instantaneous psychic elements (qualia) within the brain or as internal products of the brain.

Failure to find an obvious or linear relationship between a developmental experiential factor and a developmental outcome often leads investigators to posit concepts such as “biological preparedness” and “evolved predispositions” that allude to hypothetical geneticmechanisms that may not exist. However, experiential nonlinearities alone may explain the development of certain instinctive behaviors, as shown by studies on alarm call responsivity in mallard ducklings.

Gray, like other recent authors, seeks a scientific approach to consciousness, but fails to provide a biologically convincing description, partly because he implicitly bases his model on a computationalist foundation that embeds the contents of thought in irreducible symbolic representations. When patterns of neural activity instantiating conscious thought are shorn of homuncular observers, it appears most likely that these patterns and the circuitry that compares them with memories and plans should be found distributed over large regions of neocortex.

Davey reviews evidence purporting to distinguish between two accounts of selective associations – expectancy bias and evolved predispositions, although these hypotheses largely apply to different levels of causal analysis. Criticisms of primate studies in which subjects lack prior exposure to stimuli seem uncompelling. Expectancies may sometimes serve as proximal mediators in selective associations, but other factors, both proximate and ultimate, are clearly also involved.

There may be evolutionary as well as economic reasons why organisms generally act impulsively. I discuss this possibility and suggest some follow-up experiments that may clarify the exciting empirical and theoretical contributions made by the experiments discussed in the target article.

Recent findings emphasize the complexity, both genetic and functional, of the manifold genes and mutations causing inherited retinal degeneration in humans. Knowledge of the genetic bases of these diseases can contribute to design of rational therapy, as well as elucidating the function of each gene product in normal visual processes.

Expectations can facilitate rapid fear conditioning and this may explain some phenomena that have been attributed to preparedness. However, preparedness remains the best explanation for some aspects of clinical phobias and the difficulty of creating fears of modern dangers. Rapid fear conditioning based on expectancy is not an alternative to an evolutionary explanation, but has, like preparedness, been shaped by natural selection.

Sociopaths are “outstanding” members of society in two senses: politically, they draw our attention because of the inordinate amount of crime they commit, and psychologically, they hold our fascination because most ofus cannot fathom the cold, detached way they repeatedly harm and manipulate others. Proximate explanations from behavior genetics, child development, personality theory, learning theory, and social psychology describe a complex interaction of genetic and physiological risk factors with demographic and micro environmental variables that predispose a portion of the population to chronic antisocial behavior. More recent, evolutionary and game theoretic models have tried to present an ultimate explanation of sociopathy as the expression of a frequency-dependent life strategy which is selected, in dynamic equilibrium, in response to certain varying environmental circumstances. This paper tries to integrate the proximate, developmental models with the ultimate, evolutionary ones, suggesting that two developmentally different etiologies of sociopathy emerge from two different evolutionary mechanisms. Social strategies for minimizing the incidence of sociopathic behavior in modern society should consider the two different etiologies and the factors that contribute to them.

In this commentary, I point out some weaknesses in Gray's target article and, in the light of that discussion, I attempt to delineate the kinds of problem a cognitive neuroscience of consciousness faces on its way to a scientific understanding of subjective experience.

Rachlin's attack on the internal commitment model rests on the demonstrably false claim that self-punishment does not exist. He is correct that habits are an effective device for solving self-control problems, but his additional claim that they are the only such device makes it hard to explain how good habits develop in the first place. Someone with a self-control problem would always choose the spuriously attractive reward, which, over time, would create bad habits.