Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions

This study probes the molecular interactions between model drugs and poloxamers that facilitate dissolution rate improvements using solid dispersions. Ibuprofen and ketoprofen solid dispersions were prepared at different mole ratios using poloxamers 407 and 188. The carbonyl stretching vibration of the ibuprofen dimer shifted to higher wavenumber in the infrared spectra of 2:1 drug:carrier mole ratio solid dispersions, indicating disruption of the ibuprofen dimer concomitant with hydrogen bond formation between the drug and carrier. Solid dispersions with mole ratios >2:1 drug:carrier (up to 29:1) showed both ibuprofen hydrogen-bonded to the poloxamer, and excess drug present as dimers. X-ray diffraction studies confirmed these findings with no evidence of crystalline drug in 2:1 mole ratio systems whereas higher drug loadings retained crystalline ibuprofen. Similar results were found with ketoprofen-poloxamer solid dispersions. Thermal analysis of ibuprofen-poloxamer 407 solid dispersions and their resultant phase diagram suggested solid solutions and a eutectic system were formed, depending on drug loading. Dissolution studies showed fastest release from the solid solutions; dissolution rates from solid solutions were 12-fold greater than the dissolution of ibuprofen powder whereas the eutectic system gave a 6-fold improvement over the powder. When designing solid dispersions to improve the delivery of poorly-water soluble drugs, the nature of drug:carrier interactions, which are governed by the stochiometry of the composition, can affect the dissolution rate improvement.

Acquisition of automatic imitation is sensitive to sensorimotor contingency

The associative sequence learning model proposes that the development of the mirror system depends on the same mechanisms of associative learning that mediate Pavlovian and instrumental conditioning. To test this model, two experiments used the reduction of automatic imitation through incompatible sensorimotor training to assess whether mirror system plasticity is sensitive to contingency (i.e., the extent to which activation of one representation predicts activation of another). In Experiment 1, residual automatic imitation was measured following incompatible training in which the action stimulus was a perfect predictor of the response (contingent) or not at all predictive of the response (noncontingent). A contingency effect was observed: There was less automatic imitation indicative of more learning in the contingent group. Experiment 2 replicated this contingency effect and showed that, as predicted by associative learning theory, it can be abolished by signaling trials in which the response occurs in the absence of an action stimulus. These findings support the view that mirror system development depends on associative learning and indicate that this learning is not purely Hebbian. If this is correct, associative learning theory could be used to explain, predict, and intervene in mirror system development.

Shaking hands: Priming by social action effects

In a semi-naturalistic response-effect compatibility paradigm, participants were given the opportunity to learn that hand-shaking actions would be followed by social effects (human hand-shaking stimuli from a third-person perspective) or inanimate effects (block arrow stimuli). Relative to the actions, these effects appeared on the same or the opposite side of the screen (positional compatibility), and pointed towards or away from the response hand (directional compatibility). After learning, response times indicated a positional compatibility effect for both social and inanimate effects, but a directional compatibility effect occurred only for social action effects. These findings indicate that actions can be represented, not only by their effects on the inanimate world, but also by their effects on the actions of others. They are consistent with ideomotor theory, and with the view that actions are represented by bidirectional response-effect associations. They also have implications with respect to the origins and on-line control of imitation and the systems supporting imitation.

Action preparation helps and hinders perception of action.

Several theories of the mechanisms linking perception and action require that the links are bidirectional, but there is a lack of consensus on the effects that action has on perception. We investigated this by measuring visual event-related brain potentials to observed hand actions while participants prepared responses that were spatially compatible (e.g., both were on the left side of the body) or incompatible and action type compatible (e.g., both were finger taps) or incompatible, with observed actions. An early enhanced processing of spatially compatible stimuli was observed, which is likely due to spatial attention. This was followed by an attenuation of processing for both spatially and action type compatible stimuli, likely to be driven by efference copy signals that attenuate processing of predicted sensory consequences of actions. Attenuation was not response-modality specific; it was found for manual stimuli when participants prepared manual and vocal responses, in line with the hypothesis that action control is hierarchically organized. These results indicate that spatial attention and forward model prediction mechanisms have opposite, but temporally distinct, effects on perception. This hypothesis can explain the inconsistency of recent findings on action-perception links and thereby supports the view that sensorimotor links are bidirectional. Such effects of action on perception are likely to be crucial, not only for the control of our own actions but also in sociocultural interaction, allowing us to predict the reactions of others to our own actions.

Intact imitation of emotional facial actions in autism spectrum conditions.

It has been proposed that there is a core impairment in autism spectrum conditions (ASC) to the mirror neuron system (MNS): If observed actions cannot be mapped onto the motor commands required for performance, higher order sociocognitive functions that involve understanding another person's perspective, such as theory of mind, may be impaired. However, evidence of MNS impairment in ASC is mixed. The present study used an 'automatic imitation' paradigm to assess MNS functioning in adults with ASC and matched controls, when observing emotional facial actions. Participants performed a pre-specified angry or surprised facial action in response to observed angry or surprised facial actions, and the speed of their action was measured with motion tracking equipment. Both the ASC and control groups demonstrated automatic imitation of the facial actions, such that responding was faster when they acted with the same emotional expression that they had observed. There was no difference between the two groups in the magnitude of the effect. These findings suggest that previous apparent demonstrations of impairments to the MNS in ASC may be driven by a lack of visual attention to the stimuli or motor sequencing impairments, and therefore that there is, in fact, no MNS impairment in ASC. We discuss these findings with reference to the literature on MNS functioning and imitation in ASC, as well as theories of the role of the MNS in sociocognitive functioning in typical development.

Dynamic modulation of human motor activity when observing actions

Previous studies have demonstrated that when we observe somebody else executing an action many areas of our own motor systems are active. It has been argued that these motor activations are evidence that we motorically simulate observed actions; this motoric simulation may support various functions such as imitation and action understanding. However, whether motoric simulation is indeed the function of motor activations during action observation is controversial, due to inconsistency in findings. Previous studies have demonstrated dynamic modulations in motor activity when we execute actions. Therefore, if we do motorically simulate observed actions, our motor systems should also be modulated dynamically, and in a corresponding fashion, during action observation. Using magnetoencephalography (MEG), we recorded the cortical activity of human participants while they observed actions performed by another person. Here, we show that activity in the human motor system is indeed modulated dynamically during action observation. The finding that activity in the motor system is modulated dynamically when observing actions can explain why studies of action observation using functional magnetic resonance imaging (fMRI) have reported conflicting results, and is consistent with the hypothesis that we motorically simulate observed actions.

Learning to understand others' actions

Despite nearly two decades of research on mirror neurons, there is still much debate about what they do. The most enduring hypothesis is that they enable ‘action understanding’. However, recent critical reviews have failed to find compelling evidence in favour of this view. Instead, these authors argue that mirror neurons are produced by associative learning and therefore that they cannot contribute to action understanding. The present opinion piece suggests that this argument is flawed. We argue that mirror neurons may both develop through associative learning and contribute to inferences about the actions of others.

The role of management and landscape context in the restoration of grassland phytophagous beetles

1. Declines in area and quality of species-rich mesotrophic and calcareous grasslands have occurred all across Europe.While the European Union has promoted schemes to restore these grasslands, the emphasis for management has remained largely focused on plants. Here we focus on restoration of the phytophagous beetles of these grasslands. Although local management, particularly that which promotes the establishment of host plants, is key to restoration success, dispersal limitation is also likely to be an important limiting factor during the restoration of phytophagous beetle assemblages. 2. Using a 3-year multi-site experiment, we investigated how restoration success of phytophagous beetles was affected by hay-spreading management (intended to introduce target plant species), success in restoration of the plant communities and the landscape context within which restoration was attempted. 3. Restoration success of the plants was greatest where green hay spreading had been used to introduce seeds into restoration sites. Beetle restoration success increased over time, although hayspreading had no direct effect. However, restoration success of the beetles was positively correlated with restoration success of the plants. 4. Overall restoration success of the phytophagous beetles was positively correlated with the proportion of species-rich grassland in the landscape, as was the restoration success of the polyphagous beetles. Restoration success for beetles capable of flight and those showing oligophagous host plant specialism were also positively correlated with connectivity to species-rich grasslands. There was no indication that beetles not capable of flight showed greater dependence on landscape scale factors than flying species. 5. Synthesis and applications. Increasing the similarity of the plant community at restoration sites to target species-rich grasslands will promote restoration success for the phytophagous beetles. However, landscape context is also important, with restoration being approximately twice as successful in those landscapes containing high as opposed to low proportions of species-rich grassland. By targeting grassland restoration within landscapes containing high proportions of species-rich grassland, dispersal limitation problems associated with restoration for invertebrate assemblages are more likely to be overcome.