Maintaining internal representations: The role of the human superior parietal lobe

In sensorimotor integration, sensory input and motor output signals are combined to provide an internal estimate of the state of both the world and one's own body. Although a single perceptual and motor snapshot can provide information about the current state, computational models show that the state can be optimally estimated by a recursive process in which an internal estimate is maintained and updated by the current sensory and motor signals. These models predict that an internal state estimate is maintained or stored in the brain. Here we report a patient with a lesion of the superior parietal lobe who shows both sensory and motor deficits consistent with an inability to maintain such an internal representation between updates. Our findings suggest that the superior parietal lobe is critical for sensorimotor integration, by maintaining an internal representation of the body's state.

Topologically invariant reaction coordinates for simulating multistate chemical reactions.

Evaluating free energy profiles of chemical reactions in complex environments such as solvents and enzymes requires extensive sampling, which is usually performed by potential of mean force (PMF) techniques. The reliability of the sampling depends not only on the applied PMF method but also the reaction coordinate space within the dynamics is biased. In contrast to simple geometrical collective variables that depend only on the positions of the atomic coordinates of the reactants, the E(gap) reaction coordinate (the energy difference obtained by evaluating a suitable force field using reactant and product state topologies) has the unique property that it is able to take environmental effects into account leading to better convergence, a more faithful description of the transition state ensemble and therefore more accurate free energy profiles. However, E(gap) requires predefined topologies and is therefore inapplicable for multistate reactions, in which the barrier between the chemically equivalent topologies is comparable to the reaction activation barrier, because undesired "side reactions" occur. In this article, we introduce a new energy-based collective variable by generalizing the E(gap) reaction coordinate such that it becomes invariant to equivalent topologies and show that it yields more well behaved free energy profiles than simpler geometrical reaction coordinates.

Tests of an adaptive QM/MM calculation on free energy profiles of chemical reactions in solution.

We present reaction free energy calculations using the adaptive buffered force mixing quantum mechanics/molecular mechanics (bf-QM/MM) method. The bf-QM/MM method combines nonadaptive electrostatic embedding QM/MM calculations with extended and reduced QM regions to calculate accurate forces on all atoms, which can be used in free energy calculation methods that require only the forces and not the energy. We calculate the free energy profiles of two reactions in aqueous solution: the nucleophilic substitution reaction of methyl chloride with a chloride anion and the deprotonation reaction of the tyrosine side chain. We validate the bf-QM/MM method against a full QM simulation, and show that it correctly reproduces both geometrical properties and free energy profiles of the QM model, while the electrostatic embedding QM/MM method using a static QM region comprising only the solute is unable to do so. The bf-QM/MM method is not explicitly dependent on the details of the QM and MM methods, so long as it is possible to compute QM forces in a small region and MM forces in the rest of the system, as in a conventional QM/MM calculation. It is simple, with only a few parameters needed to control the QM calculation sizes, and allows (but does not require) a varying and adapting QM region which is necessary for simulating solutions.

"Plateau"-related summary statistics are uninformative for comparing working memory models.

Performance on visual working memory tasks decreases as more items need to be remembered. Over the past decade, a debate has unfolded between proponents of slot models and slotless models of this phenomenon (Ma, Husain, Bays (Nature Neuroscience 17, 347-356, 2014). Zhang and Luck (Nature 453, (7192), 233-235, 2008) and Anderson, Vogel, and Awh (Attention, Perception, Psychophys 74, (5), 891-910, 2011) noticed that as more items need to be remembered, "memory noise" seems to first increase and then reach a "stable plateau." They argued that three summary statistics characterizing this plateau are consistent with slot models, but not with slotless models. Here, we assess the validity of their methods. We generated synthetic data both from a leading slot model and from a recent slotless model and quantified model evidence using log Bayes factors. We found that the summary statistics provided at most 0.15 % of the expected model evidence in the raw data. In a model recovery analysis, a total of more than a million trials were required to achieve 99 % correct recovery when models were compared on the basis of summary statistics, whereas fewer than 1,000 trials were sufficient when raw data were used. Therefore, at realistic numbers of trials, plateau-related summary statistics are highly unreliable for model comparison. Applying the same analyses to subject data from Anderson et al. (Attention, Perception, Psychophys 74, (5), 891-910, 2011), we found that the evidence in the summary statistics was at most 0.12 % of the evidence in the raw data and far too weak to warrant any conclusions. The evidence in the raw data, in fact, strongly favored the slotless model. These findings call into question claims about working memory that are based on summary statistics.