Hasty sensorimotor decisions rely on an overlap of broad and selective changes in motor activity

Humans and other animals are able to adjust their speed–accuracy trade-off (SAT) at will depending on the urge to act, favoring either cautious or hasty decision policies in different contexts. An emerging view is that SAT regulation relies on influences exerting broad changes on the motor system, tuning its activity up globally when hastiness is at premium. The present study aimed to test this hypothesis. A total of 50 participants performed a task involving choices between left and right index fingers, in which incorrect choices led either to a high or to a low penalty in 2 contexts, inciting them to emphasize either cautious or hasty policies. We applied transcranial magnetic stimulation (TMS) on multiple motor representations, eliciting motor-evoked potentials (MEPs) in 9 finger and leg muscles. MEP amplitudes allowed us to probe activity changes in the corresponding finger and leg representations, while participants were deliberating about which index to choose. Our data indicate that hastiness entails a broad amplification of motor activity, although this amplification was limited to the chosen side. On top of this effect, we identified a local suppression of motor activity, surrounding the chosen index representation. Hence, a decision policy favoring speed over accuracy appears to rely on overlapping processes producing a broad (but not global) amplification and a surround suppression of motor activity. The latter effect may help to increase the signal-to-noise ratio of the chosen representation, as supported by single-trial correlation analyses indicating a stronger differentiation of activity changes in finger representations in the hasty context.

Many have argued that the regulation of the speed-accuracy tradeoff relies on an urgency signal, which implements "collapsing decision thresholds" by tuning neural activity in a global manner in decision-related structures. This study indicates that the reality is more subtle, with several aspects of "urgency" being specifically targeted to particular corticospinal populations within the motor system.     

A remarkable facilitating effect of parietal damage

When distracters conflict with our instructions, our reactions normally get slower. However, Coulthard and colleagues in this issue of Neuron show that damage to the right parietal lobe reverses this effect, paradoxically facilitating responses. This surprising result may shed light on the functional role of parietal cortex within a larger cortical circuit for voluntary behavior.     

Altered phosphorylation pattern of simian virus 40 T antigen expressed in insect cells by using a baculovirus vector.

The phosphorylation pattern of simian virus 40 (SV40) large tumor (T) antigen purified from insect cells infected with a recombinant baculovirus was compared with that reported previously for T antigen from SV40-infected monkey cells. The specific activity of metabolic phosphate labeling of baculovirus T antigen was reduced, and the phosphopeptide map of the baculovirus protein, while qualitatively similar to that of lytic T, revealed several quantitative differences. The most striking difference was the prominence in the baculovirus map of peptides containing phosphothreonine 124. These peptides are known to arise from other phosphopeptides upon dephosphorylation of neighboring serines, suggesting that baculovirus T may be underphosphorylated at these serines and perhaps other sites. Functional assays used to further investigate the phosphorylation state of the baculovirus protein included SV40 DNA binding after enzymatic dephosphorylation with alkaline phosphatase and after phosphorylation by a murine homolog of cdc2 protein kinase. The results imply that baculovirus T antigen is underphosphorylated, in particular at those serine residues whose phosphorylation is responsible for down regulation of DNA-binding activity at site II in the core origin of DNA replication. In contrast, no evidence for a functionally significant underphosphorylation at threonine 124 could be found.     

Spiking neurons that keep the rhythm

Detecting the temporal relationship among events in the environment is a fundamental goal of the brain. Following pulses of rhythmic stimuli, neurons of the retina and cortex produce activity that closely approximates the timing of an omitted pulse. This omitted stimulus response (OSR) is generally interpreted as a transient response to rhythmic input and is thought to form a basis of short-term perceptual memories. Despite its ubiquity across species and experimental protocols, the mechanisms underlying OSRs remain poorly understood. In particular, the highly transient nature of OSRs, typically limited to a single cycle after stimulation, cannot be explained by a simple mechanism that would remain locked to the frequency of stimulation. Here, we describe a set of realistic simulations that capture OSRs over a range of stimulation frequencies matching experimental work. The model does not require an explicit mechanism for learning temporal sequences. Instead, it relies on spike timing-dependent plasticity (STDP), a form of synaptic modification that is sensitive to the timing of pre- and post-synaptic action potentials. In the model, the transient nature of OSRs is attributed to the heterogeneous nature of neural properties and connections, creating intricate forms of activity that are continuously changing over time. Combined with STDP, neural heterogeneity enabled OSRs to complex rhythmic patterns as well as OSRs following a delay period. These results link the response of neurons to rhythmic patterns with the capacity of heterogeneous circuits to produce transient and highly flexible forms of neural activity.     

Regioselective reaction of thiols with catechol estrogens and estrogen-O-quinones

Incubations of [3H]estradiol and [3H]2-hydroxyestradiol (2-OHE2) with rat liver microsomes and mushroom tyrosinase were carried out in the presence of glutathione and 2-mercaptoethanol. A ratio of about 3.5:1 for the C-4 and C-1 thioether conjugates of 2-OHE2 was observed. Chemical reaction of estradiol-2, 3-O-quinone with various thiols showed that alkyl and phenyl thiols gave about a 1:1 ratio of C-4 to C-1 thioethers. However, reaction of the O-quinone with 4-nitrothiophenol gave a C-4/C-1 ratio of 0.25 while 4-bromothiophenol gave a C-4/C-1 ratio of 4.0. These studies suggest that the regioselectivity of the reaction of thiols with estrogen catechols and O-quinones may be dependent on the nature of the thiol compounds and less on steric hindrance.     

On the challenges and mechanisms of embodied decisions

Neurophysiological studies of decision-making have focused primarily on elucidating the mechanisms of classic economic decisions, for which the relevant variables are the values of expected outcomes and action is simply the means of reporting the selected choice. By contrast, here we focus on the particular challenges of embodied decision-making faced by animals interacting with their environment in real time. In such scenarios, the choices themselves as well as their relative costs and benefits are defined by the momentary geometry of the immediate environment and change continuously during ongoing activity. To deal with the demands of embodied activity, animals require an architecture in which the sensorimotor specification of potential actions, their valuation, selection and even execution can all take place in parallel. Here, we review behavioural and neurophysiological data supporting a proposed brain architecture for dealing with such scenarios, which we argue set the evolutionary foundation for the organization of the mammalian brain.     

Cortical mechanisms of action selection: the affordance competition hypothesis

At every moment, the natural world presents animals with two fundamental pragmatic problems: selection between actions that are currently possible and specification of the parameters or metrics of those actions. It is commonly suggested that the brain addresses these by first constructing representations of the world on which to build knowledge and make a decision, and then by computing and executing an action plan. However, neurophysiological data argue against this serial viewpoint. In contrast, it is proposed here that the brain processes sensory information to specify, in parallel, several potential actions that are currently available. These potential actions compete against each other for further processing, while information is collected to bias this competition until a single response is selected. The hypothesis suggests that the dorsal visual system specifies actions which compete against each other within the fronto-parietal cortex, while a variety of biasing influences are provided by prefrontal regions and the basal ganglia. A computational model is described, which illustrates how this competition may take place in the cerebral cortex. Simulations of the model capture qualitative features of neurophysiological data and reproduce various behavioural phenomena.     

Structure-activity relationship of cyclic thiacarbocyanine tau aggregation inhibitors

Macrocyclic bis-thiacarbocyanines are efficacious inhibitors of tau protein aggregation. To extend the structure-activity relationship of this inhibitor class, N,N’-alkylene bis-thiacarbocyanines linked by chains of three to eight methylene carbons were synthesized and examined for inhibitory activity against recombinant human tau aggregation in vitro. At 10 micromolar concentration, inhibitory activity varied with linker length, with four methylene units being most efficacious. On the basis of absorbance spectroscopy measurements, linker length also affected compound folding and aggregation propensity, with a linker length of four methylene units being optimal for preserving open monomer conformation. These data suggest that inhibitory potency can be optimized through control of linker length, and that a contributory mechanism involves modulation of compound folding and aggregation.