Motor versus body awareness: Voxel-based lesion analysis in anosognosia for hemiplegia and somatoparaphrenia following right hemisphere stroke

This is the accepted manuscript version of the following article: Valentina Moro, Simone Pernigo, Manos Tsakiris, Renato Avesani, Nicola M. J. Edelstyn, Paul M. Jenkinson, and Aikaterini Fotopoulou, ‘Motor versus body awareness: Voxel-based lesion analysis in anosognosia for hemiplegia and somatoparaphrenia following right hemisphere stroke’, Cortex, Vol 83, pp. 62-77, first published online 15 Jul 2016. The version of record is available online at doi: http://dx.doi.org/10.1016/j.cortex.2016.07.001 Published by Elsevier. © Elsevier Ltd. All rights reserved.Anosognosia for hemiplegia (AHP) is informative about the neurocognitive basis of motor awareness. However, it is frequently associated with concomitant symptoms, such as hemispatial neglect and disturbances in the sense of body ownership (DSO). Although double dissociations between these symptoms have been reported, there is ongoing debate about whether they are manifestations of independent abnormalities, or a single neuro- cognitive deficit. We aimed to investigate the specificity of lesions associated with AHP by surpassing four, existing methodological limitations: (a) recruit a relatively large sample of patients (total N 1⁄4 70) in a multi-centre study; (b) identify lesions associated with AHP in grey and white matter using voxel-based methods; (c) take into account the duration of AHP and concomitant neglect symptoms; and (d) compare lesions against a control hemiplegic group, patients suffering from AHP and DSO, and a few, rare patients with selective DSO. Results indicated that acute AHP is associated with a wide network, mainly including: (1) the Rolandic operculum, (2) the insula and (3) the superior temporal gyri. Subcortically, damage mainly involved the basal ganglia and white matter, mostly the superior corona radiate, arcuate fasciculus and the part of the ventral, superior longitu- dinal fasciculus. Persistent symptoms were linked with wider damage involving fronto- temporal cortex and long white matter tracts. A shift in the latero-medial direction (mainly involving the basal ganglia and surrounding white matter) emerged when DSO was taken accounted for. These results suggest that while bodily awareness is processed by areas widely distributed across the brain, intact subcortical structures and white matter tracts may be necessary to support basic feelings of owning and controlling contralateral body parts. An accurate and ‘up-to-date’ awareness of our motor abilities, however, may rely also on intact processing in cortical areas which presumably allow higher-order in- ferences about the current state of the body.Peer reviewedFinal Accepted Versio

Frame rate required for speckle tracking echocardiography: A quantitative clinical study with open-source, vendor-independent software

Background Assessing left ventricular function with speckle tracking is useful in patient diagnosis but requires a temporal resolution that can follow myocardial motion. In this study we investigated the effect of different frame rates on the accuracy of speckle tracking results, highlighting the temporal resolution where reliable results can be obtained. Material and methods 27 patients were scanned at two different frame rates at their resting heart rate. From all acquired loops, lower temporal resolution image sequences were generated by dropping frames, decreasing the frame rate by up to 10-fold. Results Tissue velocities were estimated by automated speckle tracking. Above 40 frames/s the peak velocity was reliably measured. When frame rate was lower, the inter-frame interval containing the instant of highest velocity also contained lower velocities, and therefore the average velocity in that interval was an underestimate of the clinically desired instantaneous maximum velocity. Conclusions The higher the frame rate, the more accurately maximum velocities are identified by speckle tracking, until the frame rate drops below 40 frames/s, beyond which there is little increase in peak velocity. We provide in an online supplement the vendor-independent software we used for automatic speckle-tracked velocity assessment to help others working in this field

Cytoskeletal protein kinases: titin and its relations in mechanosensing

Titin, the giant elastic ruler protein of striated muscle sarcomeres, contains a catalytic kinase domain related to a family of intrasterically regulated protein kinases. The most extensively studied member of this branch of the human kinome is the Ca2+–calmodulin (CaM)-regulated myosin light-chain kinases (MLCK). However, not all kinases of the MLCK branch are functional MLCKs, and about half lack a CaM binding site in their C-terminal autoinhibitory tail (AI). A unifying feature is their association with the cytoskeleton, mostly via actin and myosin filaments. Titin kinase, similar to its invertebrate analogue twitchin kinase and likely other “MLCKs”, is not Ca2+–calmodulin-activated. Recently, local protein unfolding of the C-terminal AI has emerged as a common mechanism in the activation of CaM kinases. Single-molecule data suggested that opening of the TK active site could also be achieved by mechanical unfolding of the AI. Mechanical modulation of catalytic activity might thus allow cytoskeletal signalling proteins to act as mechanosensors, creating feedback mechanisms between cytoskeletal tension and tension generation or cellular remodelling. Similar to other MLCK-like kinases like DRAK2 and DAPK1, TK is linked to protein turnover regulation via the autophagy/lysosomal system, suggesting the MLCK-like kinases have common functions beyond contraction regulation

Structures of insect Imp-L2 suggest an alternative strategy for regulating the bioavailability of insulin-like hormones

The insulin/insulin-like growth factor signalling axis is an evolutionary ancient and highly conserved hormonal system involved in the regulation of metabolism, growth and lifespan in animals. Human insulin is stored in the pancreas, while insulin-like growth factor-1 (IGF-1) is maintained in blood in complexes with IGF-binding proteins (IGFBP1–6). Insect insulin-like polypeptide binding proteins (IBPs) have been considered as IGFBP-like structural and functional homologues. Here, we report structures of the Drosophila IBP Imp-L2 in its free form and bound to Drosophila insulin-like peptide 5 and human IGF-1. Imp-L2 contains two immunoglobulin-like fold domains and its architecture is unrelated to human IGFBPs, suggesting a distinct strategy for bioavailability regulation of insulin-like hormones. Similar hormone binding modes may exist in other insect vectors, as the IBP sequences are highly conserved. Therefore, these findings may open research routes towards a rational interference of transmission of diseases such as malaria, dengue and yellow fevers

Structural basis for kinesin-1:cargo recognition

Kinesin-mediated cargo transport is required for many cellular functions and plays a key role in pathological processes. Structural information on how kinesins recognize their cargoes is required for a molecular understanding of this fundamental and ubiquitous process. Here, we present the crystal structure of the tetratricopeptide repeat domain of kinesin light chain 2 in complex with a cargo peptide harboring a "tryptophan-acidic" motif derived from SKIP (SifA-kinesin interacting protein), a critical host determinant in Salmonella pathogenesis and a regulator of lysosomal positioning. Structural data together with biophysical, biochemical, and cellular assays allow us to propose a framework for intracellular transport based on the binding by kinesin-1 of W-acidic cargo motifs through a combination of electrostatic interactions and sequence-specific elements, providing direct molecular evidence of the mechanisms for kinesin-1:cargo recognition

The Neural Basis of Body Form and Body Action Agnosia

Visual analysis of faces and nonfacial body stimuli brings about neural activity in different cortical areas. Moreover, processing body form and body action relies on distinct neural substrates. Although brain lesion studies show specific face processing deficits, neuropsychological evidence for defective recognition of nonfacial body parts is lacking. By combining psychophysics studies with lesion-mapping techniques, we found that lesions of ventromedial, occipitotemporal areas induce face and body recognition deficits while lesions involving extrastriate body area seem causatively associated with impaired recognition of body but not of face and object stimuli. We also found that body form and body action recognition deficits can be double dissociated and are causatively associated with lesions to extrastriate body area and ventral premotor cortex, respectively. Our study reports two category-specific visual deficits, called body form and body action agnosia, and highlights their neural underpinnings

OPTICAL BISTABILITY WITH RYDBERG ATOMS

On présente une expérience sur la bistabilité optique d'absorption à un nombre extrêmement petit de photons et d'atomes. On s'y sert du couplage fort entre des atomes Rb de Rydberg et le champ électrique à l'intérieur d'une cavité supraconductrice de micro-ondes. Cela permet d'étudier l'influence des fluctuations sur le comportement d'un système bistable.We present an experiment on absorptive optical bistability at extremely low photon and atom numbers, making use of the strong coupling of Rydberg Rb atoms to the electric field in a superconducting microwave cavity. This allows to study the influence of fluctuations on the behaviour of a bistable device

The light chains of kinesin-1 are autoinhibited

The light chains (KLCs) of the microtubule motor kinesin-1 bind cargoes and regulate its activity. Through their tetratricopeptide repeat domain (KLCTPR), they can recognize short linear peptide motifs found in many cargo proteins characterized by a central tryptophan flanked by aspartic/glutamic acid residues (W-acidic). Using a fluorescence resonance energy transfer biosensor in combination with X-ray crystallographic, biochemical, and biophysical approaches, we describe how an intramolecular interaction between the KLC2TPR domain and a conserved peptide motif within an unstructured region of the molecule, partly occludes the W-acidic binding site on the TPR domain. Cargo binding displaces this interaction, effecting a global conformational change in KLCs resulting in a more extended conformation. Thus, like the motor-bearing kinesin heavy chains, KLCs exist in a dynamic conformational state that is regulated by self-interaction and cargo binding. We propose a model by which, via this molecular switch, W-acidic cargo binding regulates the activity of the holoenzyme

Massive somatic deafferentation and motor deefferentationof the lower part of the body impair its visual recognition: apsychophysical study of patients with spinal cord injury

Embodied cognition theories postulate that perceiving and understanding the body states of other individuals are underpinned by the neural structures activated during first-hand experience of the same states. This suggests that one\u2019s own sensorimotor system may be used to identify the actions and sensations of others. Virtual and real brain lesion studies show that visual processing of body action and body form relies upon neural activity in the ventral premotor and the extrastriate body areas, respectively. We explored whether visual body perception may also be altered in the absence of damage to the above cortical regions by testing healthy controls and spinal cord injury (SCI) patients whose brain was unable to receive somatic information from and send motor commands to the lower limbs. Participants performed tasks investigating the ability to visually discriminate changes in the form or action of body parts affected by somatosensory and motor disconnection. SCI patients showed a specific, cross-modal deficit in the visual recognition of the disconnected lower body parts. This deficit affected both body action and body form perception, hinting at a pervasive influence of ongoing body signals on the brain network dedicated to visual body processing. Testing SCI patients who did or did not practise sports allowed us to test the influence of motor practice on visual body recognition. We found better upper body action recognition in sport-practising SCI patients, indicating that motor practice is useful for maintaining visual representation of actions after deafferentation and deefferentation. This may be a potential resource to be exploited for rehabilitation

Fokker-Planck description of stochastic processes with colored noise.

A detailed theoretical discussion is presented of the effect of colored noise on nonlinear dynamical systems. The ideas arising from it are applied to a particular example of such a system: a model of dispersive optical bistability, considered in the contexts of both additive and multiplicative forcing. Analogue experiments and digital simulation techniques are used to explore the applicability and range of validity of theories proposed to date. The physical phenomenon of bimodality induced by the finite bandwidth (alone) of additive forcing is demonstrated in detail for the first time. The three existing theories capable of accounting for this phenomenon can each be categorized in terms of a single (constant) value of a characteristic parameter Pexp; but it is shown that, in reality, Pexpt varies weakly with the correlation time tau of the noise. The variation of Pexp, with tau is investigated in the currently accessible range of O.1<tau<infinity