Rhythm makes the world go round:an MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally “embodying” another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general.

Characterising the central mechanisms of sensory modulation in human swallowing motor cortex

Objective: Pharyngeal stimulation can induce remarkable increases in the excitability of swallowing motor cortex, which is associated with short-term improvements in swallowing behaviour in dysphagic stroke patients. However, the mechanism by which this input induces cortical change remains unclear. Our aims were to explore the stimulus-induced facilitation of the cortico-bulbar projections to swallowing musculature and examine how input from the pharynx interacts with swallowing motor cortex. Methods: In 8 healthy subjects, a transcranial magnetic stimulation (TMS) paired-pulse investigation was performed comprising a single conditioning electrical pharyngeal stimulus (pulse width 0.2 ms, 240 V) followed by cortical TMS at inter-stimulus intervals (ISI) of 10-100 ms. Pharyngeal sensory evoked potentials (PSEP) were also measured over the vertex. In 6 subjects whole-brain magnetoencephalography (MEG) was further acquired following pharyngeal stimulation. Results: TMS evoked pharyngeal motor evoked potentials were facilitated by the pharyngeal stimulus at ISI between 50 and 80 ms (Δ mean increase: 47±6%, P<0.05). This correlated with the peak latency of the P1 component of the PSEP (mean 79.6±8.5 ms). MEG confirmed that the equivalent P1 peak activities were localised to caudolateral sensory and motor cortices (BA 4, 1, 2). Conclusions: Facilitation of the cortico-bulbar pathway to pharyngeal stimulation relates to coincident afferent input to sensorimotor cortex. Significance: These findings have mechanistic importance on how pharyngeal stimulation may increase motor excitability and provide guidance on temporal windows for future manipulations of swallowing motor cortex. © 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ligand binding and activation of the CGRP receptor

The receptor for CGRP (calcitonin gene-related peptide) is a heterodimer between a GPCR (G-protein-coupled receptor), CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). Models have been produced of RAMP1 and CLR. It is likely that the C-terminus of CGRP interacts with the extracellular N-termini of CLR and RAMP1; the extreme N-terminus of CLR is particularly important and may interact directly with CGRP and also with RAMP1. The N-terminus of CGRP interacts with the TM (transmembrane) portion of the receptor; the second ECL (extracellular loop) is especially important. Receptor activation is likely to involve the relative movements of TMs 3 and 6 to create a G-protein-binding pocket, as in Family A GPCRs. Pro321 in TM6 appears to act as a pivot. At the base of TMs 2 and 3, Arg151, His155 and Glu211 may form a loose equivalent of the Family A DRY (Asp-Arg-Tyr) motif. Although the details of this proposed activation mechanism clearly do not apply to all Family B GPCRs, the broad outlines may be conserved. ©The Authors.

Solvent induced NMR chemical shifts that arise from molecular encounters

Recently Homer and Percival have postulated that intermolecular van der Waals dispersion forces can be characterized by three mechanisms. The first arises via the mean square reaction field < R1; 2> due to the transient dipole of a particular solute molecule that is considered situated in a cavity surrounded by solvent molecules; this was characterized by an extended Onsager approach. The second stems from the extra cavity mean square reaction field < R2; 2> of the near neighbour solvent molecules. The third originates from square field electric fields E2BI due to a newly characterized effect in which solute atoms are `buffeted' by the peripheral atoms of adjacent solvent molecules. The present work concerns more detailed studies of the buffeting screening, which is governed by sterically controlled parameter (2T - T)2, where and are geometric structural parameters. The original approach is used to characterise the buffeting shifts induced by large solvent molecules and the approach is found to be inadequate. Consequently, improved methods of calculating and are reported. Using the improved approach it is shown that buffeting is dependent on the nature of the solvent as well as the nature of the solute molecule. Detailed investigation of the buffeting component of the van der Waals chemical shifts of selected solutes in a range of solvents containing either H or Cl as peripheral atoms have enabled the determination of a theoretical acceptable value for the classical screening coefficient B for protons. 1H and 13C resonance studies of tetraethylmethane and 1H, 13C and 29Si resonance studies of TMS have been used to support the original contention that three (< R1; 2> , < R2; 2> and E2BI) components of intermolecular van der Waals dispersion fields are required to characterise vdW chemical shifts.

Studies of the effects of molecular encounters on N.M.R. spin-lattice relaxation times

This thesis is concerned with investigations of the effects of molecular encounters on nuclear magnetic resonance spin-lattice relaxation times, with particular reference to mesitylene in mixtures with cyclohexane and TMS. The purpose of the work was to establish the best theoretical description of T1 and assess whether a recently identified mechanism (buffeting), that influences n.m.r. chemical shifts, governs Tl also. A set of experimental conditions are presented that allow reliable measurements of Tl and the N. O. E. for 1H and 13C using both C. W. and F.T. n.m.r. spectroscopy. Literature data for benzene, cyclohexane and chlorobenzene diluted by CC14 and CS2 are used to show that the Hill theory affords the best estimation of their correlation times but appears to be mass dependent. Evaluation of the T1 of the mesitylene protons indicates that a combined Hill-Bloembergen-Purcell-Pound model gives an accurate estimation of T1; subsequently this was shown to be due to cancellation of errors in the calculated intra and intemolecular components. Three experimental methods for the separation of the intra and intermolecular relaxation times are described. The relaxation times of the 13C proton satellite of neat bezene, 1,4 dioxane and mesitylene were measured. Theoretical analyses of the data allow the calculation of Tl intra. Studies of intermolecular NOE's were found to afford a general method of separating observed T1's into their intra and intermolecular components. The aryl 1H and corresponding 13C T1 values and the NOE for the ring carbon of mesitylene in CC14 and C6H12-TMS have been used in combination to determine T1intra and T1inter. The Hill and B.P.P. models are shown to predict similarly inaccurate values for T1linter. A buffeting contribution to T1inter is proposed which when applied to the BPP model and to the Gutowsky-Woessner expression for T1inter gives an inaccuracy of 12% and 6% respectively with respect to theexperimentally based T1inter.

Cognitive neuroscience and (very) high level vision

THE PURPOSE OF THIS ARTICLE is two-fold, first to provide a general overview of two of the main cognitive neuroscientific techniques available, specifically functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS); and secondly to apply these techniques to elaborate a discussion of an aspect of higher level vision, namely implied motion, that is the perception of movement from a static image.

Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function

The first and third extracellular loops (ECL) of G protein-coupled receptors (GPCRs) have been implicated in ligand binding and receptor function. This study describes the results of an alanine/leucine scan of ECLs 1 and 3 and loop-associated transmembrane (TM) domains of the secretin-like GPCR calcitonin receptor-like receptor which associates with receptor activity modifying protein 1 to form the CGRP receptor. Leu195Ala, Val198Ala and Ala199Leu at the top of TM2 all reduced aCGRP-mediated cAMP production and internalization; Leu195Ala and Ala199Leu also reduced aCGRP binding. These residues form a hydrophobic cluster within an area defined as the "minor groove" of rhodopsin-like GPCRs. Within ECL1, Ala203Leu and Ala206Leu influenced the ability of aCGRP to stimulate adenylate cyclase. In TM3, His219Ala, Leu220Ala and Leu222Ala have influences on aCGRP binding and cAMP production; they are likely to indirectly influence the binding site for aCGRP as well as having an involvement in signal transduction. On the exofacial surfaces of TMs 6 and 7, a number of residues were identified that reduced cell surface receptor expression, most noticeably Leu351Ala and Glu357Ala in TM6. The residues may contribute to the RAMP1 binding interface. Ile360Ala impaired aCGRP-mediated cAMP production. Ile360 is predicted to be located close to ECL2 and may facilitate receptor activation. Identification of several crucial functional loci gives further insight into the activation mechanism of this complex receptor system and may aid rational drug design.

Investigating central mechanisms underlying the effects of action observation and imagery through transcranial magnetic stimulation

Sport and exercise psychologists provide some interventions for clients based on limited direct evidence and partial understanding of the mechanisms that underpin their efficacy. The authors review a recent technique, transcranial magnetic stimulation (TMS), which offers a tested procedure for investigating cortical activity during observation and imagery processes. They provide a detailed description of the TMS protocol and highlight some of the key studies that inform sport and exercise psychology research. Finally, the authors offer some thoughts on the direct application to practice.

Prior action execution has no effect on corticospinal facilitation during action observation

Transcranial magnetic stimulation (TMS) has been used widely in research investigating corticospinal (CS) excitability during action observation. Generally, this work has shown that observation of an action performed by others, in the absence of overt movement, modulates the excitability of the CS pathway in humans. Despite the extent of the literature exploring action observation effects, however, there has been little research to date that has compared observation with the combination of observation and execution directly. Here, we report a single-pulse TMS study that investigated whether CS excitability during action observation was modulated by actions performed by the observers prior to viewing a ball pinching action. The results showed that CS excitability during action observation increased when compared to observation of a static hand, but that there was no additional motor facilitation when participants performed the same action prior to observing it. Our findings highlight the importance of action observation and its consequences on the CS system, whilst also illustrating the limited effect of prior action execution on the CS pathway for a simple action task.

Lifting the lid on GPCRs:the role of extracellular loops

GPCRs exhibit a common architecture of seven transmembrane helices (TMs) linked by intracellular loops and extracellular loops (ECLs). Given their peripheral location to the site of G-protein interaction, it might be assumed that ECL segments merely link the important TMs within the helical bundle of the receptor. However, compelling evidence has emerged in recent years revealing a critical role for ECLs in many fundamental aspects of GPCR function, which supported by recent GPCR crystal structures has provided mechanistic insights. This review will present current understanding of the key roles of ECLs in ligand binding, activation and regulation of both family A and family B GPCRs.

Reflecting on mirror mechanisms:motor resonance effects during action observation only present with low-intensity transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) studies indicate that the observation of other people's actions influences the excitability of the observer's motor system. Motor evoked potential (MEP) amplitudes typically increase in muscles which would be active during the execution of the observed action. This 'motor resonance' effect is thought to result from activity in mirror neuron regions, which enhance the excitability of the primary motor cortex (M1) via cortico-cortical pathways. The importance of TMS intensity has not yet been recognised in this area of research. Low-intensity TMS predominately activates corticospinal neurons indirectly, whereas high-intensity TMS can directly activate corticospinal axons. This indicates that motor resonance effects should be more prominent when using low-intensity TMS. A related issue is that TMS is typically applied over a single optimal scalp position (OSP) to simultaneously elicit MEPs from several muscles. Whether this confounds results, due to differences in the manner that TMS activates spatially separate cortical representations, has not yet been explored. In the current study, MEP amplitudes, resulting from single-pulse TMS applied over M1, were recorded from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles during the observation of simple finger abductions. We tested if the TMS intensity (110% vs. 130% resting motor threshold) or stimulating position (FDI-OSP vs. ADM-OSP) influenced the magnitude of the motor resonance effects. Results showed that the MEP facilitation recorded in the FDI muscle during the observation of index-finger abductions was only detected using low-intensity TMS. In contrast, changes in the OSP had a negligible effect on the presence of motor resonance effects in either the FDI or ADM muscles. These findings support the hypothesis that MN activity enhances M1 excitability via cortico-cortical pathways and highlight a methodological framework by which the neural underpinnings of action observation can be further explored. © 2013 Loporto et al.

Are we on the same page? Knowledge boundaries and transactive memory system development in cross-functional teams

One of the key challenges that organizations face when trying to integrate knowledge across different functions is the need to overcome knowledge boundaries between team members. In cross-functional teams, these boundaries, associated with different knowledge backgrounds of people from various disciplines, create communication problems, necessitating team members to engage in complex cognitive processes when integrating knowledge toward a joint outcome. This research investigates the impact of syntactic, semantic, and pragmatic knowledge boundaries on a team’s ability to develop a transactive memory system (TMS)—a collective memory system for knowledge coordination in groups. Results from our survey show that syntactic and pragmatic knowledge boundaries negatively affect TMS development. These findings extend TMS theory beyond the information-processing view, which treats knowledge as an object that can be stored and retrieved, to the interpretive and practice-based views of knowledge, which recognize that knowledge (in particular specialized knowledge) is localized, situated, and embedded in practice.

Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex

We evaluated inter-individual variability in optimal current direction for biphasic transcranial magnetic stimulation (TMS) of the motor cortex. Motor threshold for first dorsal interosseus was detected visually at eight coil orientations in 45° increments. Each participant (n = 13) completed two experimental sessions. One participant with low test–retest correlation (Pearson's r < 0.5) was excluded. In four subjects, visual detection of motor threshold was compared to EMG detection; motor thresholds were very similar and highly correlated (0.94–0.99). Similar with previous studies, stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our sample the optimal orientation of current direction was normally distributed around the postero-lateral orientation with a range of 63° (S.D. = 13.70°). Whenever the intensity of stimulation at the target site is calculated as a percentage from the motor threshold, in order to minimize intensity and side-effects it may be worthwhile to check whether rotating the coil 45° from the traditional posterior–lateral orientation decreases motor threshold.

Current knowledge on the role of the inferior frontal gyrus in Theory of Mind - a commentary on Schurz and Tholen (2016)

Schurz and Tholen (2016) argue that common approaches to studying the neural basis of “theory of mind” (ToM) obscure a potentially important role for inferior frontal gyrus (IFG) in managing conflict between perspectives, and urge new work to address this question: “to gain a full understanding of the IFG's role in ToM, we encourage future imaging studies to use a wider range of control conditions.” (p332). We wholeheartedly agree, but note that this observation has been made before, and has already led to a programme of work that provides evidence from fMRI, EEG, and TMS on the role of IFG in managing conflict between self and other perspectives in ToM. We highlight these works, and in particular we demonstrate how careful manipulation within ToM tasks has been used to act as an internal control condition, wherein conflict has been manipulated within-subject. We further add to the discussion by framing key questions that remain regarding IFG in the context of these. Using limitations in the existing research, we outline how best researchers can proceed with the challenge set by Schurz and Tholen (2016).