From rubber hands to neuroprosthetics: Neural correlates of embodiment

© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Our interaction with the world rests on the knowledge that we are a body in space and time, which can interact with the environment. This awareness is usually referred to as sense of embodiment. For the good part of the past 30 years, the rubber hand illusion (RHI) has been a prime tool to study embodiment in healthy and people with a variety of clinical conditions. In this paper, we provide a critical overview of this research with a focus on the RHI paradigm as a tool to study prothesis embodiment in individuals with amputation. The RHI relies on well-documented multisensory integration mechanisms based on sensory precision, where parietal areas are involved in resolving the visuo-tactile conflict, and premotor areas in updating the conscious bodily representation. This mechanism may be transferable to prosthesis ownership in amputees. We discuss how these results might transfer to technological development of sensorised prostheses, which in turn might progress the acceptability by users.Peer reviewe

Intermittent Theta Burst Stimulation Over Ventral Premotor Cortex or Inferior Parietal Lobule Does Not Enhance the Rubber Hand Illusion

An enhanced sense of prosthesis ownership may be the key for higher amputees’ quality of life. In this study in 28 healthy subjects, neuronavigated intermittent Theta Burst Stimulation (iTBS) delivered over the right ventral premotor cortex or inferior parietal lobule has been tested, compared to sham stimulation, to enhance embodiment in the rubber hand illusion paradigm. Neuromodulation of both areas did not result in an enhancement of embodiment, as assessed by the results collected from a self-evaluation questionnaire for the extent of self-attribution of the rubber hand and proprioceptive drift. In all cases, the difference between synchronous and asynchronous stroking confirms the successful induction of the illusion. It may be speculated that the low consistency of iTBS over brain regions other than primary motor cortex may account for the absence of effect, suggesting to test other neuromodulating techniques, acting on cortical networks different from the ones sensitive to iTBS to enhance artificial hand embodiment

Halophenol bioremediation catalyzed by an artificial peroxidase

Halophenols (HPs) have been widely used as pesticides, herbicides and wood-preserving agents. Once released into the environment, they exert toxic effects onto living systems such as plants, animals and humans.[1] Among bioremediation strategies targeting HPs, oxidative degradation is efficiently catalyzed by natural heme-enzymes, such as Horseradish Peroxidase (HRP),[2,3] in the presence of hydrogen peroxide as an oxidant. Peroxidases activate the phenol ring, by generating both phenoxy radical and carbocationic species, which further react to give coupling and/or oxidative dehalogenation products, such as chlorinated benzo-p-dioxins and quinones. The ability of these enzymes to cause phenolic coupling may allow the immobilization of toxic phenolic substances, such as HPs, limiting their bioavailability and suppressing their toxic effects. Humic acids (HA) are ubiquitous organic materials in terrestrial and aquatic ecosystems to which HPs can covalenty bind upon activation. In order to improve the chemical stability of natural peroxidases along with their catalytic efficiency, in recent years a variety of artificial biomimetic systems has been developed and evaluated to this purpose. [4] In this area, our ongoing project, focused on the design and synthesis of artificial enzymes led us to explore the activity of an artificial peroxidase, FeIII-Mimochrome VI*a (FeMC6*a), towards HPs.[5] Herein, the oxidative degradation of HPs catalyzed by FeMC6*a and its use in bioremediation strategies are reported. FeMC6*a is able to convert a variety of HPs, including 2,4,6-trichlorophenol (TCP) with 840-fold higher catalytic efficiency than natural HRP. 1. J. Huff, Chemosphere 2012, 89, 521. 2. S. Sumithran, M. Sono, G. M. Raner, J. H. Dawson, J. Inorg. Biochem. 2012, 117, 316. 3. K. Morimoto, K.Tatsumi, K-I Kuroda, Soil Biology & Biochemistry 2000, 32, 1071. 4. M. Chino, L. Leone, G. Zambrano, F. Pirro, D. D’Alonzo, V. Firpo, D. Aref, L. Lista, O. Maglio, F. Nastri, A. Lombardi, Biopolymers, 2018, e23107. 5. G. Caserta, M. Chino, V. Firpo, G. Zambrano, L. Leone, D. D’Alonzo, F. Nastri, O. Maglio, V. Pavone, A. Lombardi, ChemBioChem 2018, cbic.201800200

A biomimetic metalloporphyrin catalyzes indole oxidation with high selectivity

Indole is one of the most common heterocyclic scaffolds available in nature. It occurs in several natural compounds, including alkaloids, plant hormones, flower scents and dyes.1 Despite the structural simplicity of this molecule, indole oxidation commonly results in the formation of a large number of products, including the 2- or 3-oxygenated compounds, di-oxygenated and more complex molecules. For this reason, indole oxidation has become a widespread model reaction to test the efficacy of both biological catalysts2,3 and their synthetic analogues.4,5 Most of the catalysts examined so far gave poor selectivity toward any of the oxidation products.2-5 Here we present the results concerning oxidation of indole and its derivatives catalyzed by Mn-Mimochrome VI*a (Mn-MC6*a). Mn-MC6*a is a synthetic peptide-porphyrin conjugate conceived to act as a miniaturized heme-protein model.6 Mn-MC6*a is able to oxidize indole under unprecedented site-selective conditions, yielding to 3-oxindolenine as single product. Additionally, the reaction selectivity is dramatically altered when 1- or 3-methyl-substituted indoles are used as substrates. The formation and isolation of the reactive 3-oxindolenine is highly important, since it is believed to represent a useful synthon in organic synthesis. Accordingly, the exploitation of its reactivity with nucleophiles, in order to provide one pot transformations, is currently ongoing, with the aim to further increase the synthetic potential of our catalyst. 1. Burton, T.C. in Heterocyclic scaffolds II: Reactions and applications of indoles; Gribble, G.W., Ed.; Springer-Verlag Berlin Heidelberg, 2011. 2. Kuo, H. H. and Mauk, A. G.; Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 13966–13971. 3. Barrios, D. A. et al. J. Am. Chem. Soc. 2014, 136, 7914-7925. 4. Linhares, M. et al. Appl. Catal. A. 2014, 470, 427–433. 5. Poon L. C.-H. et al. J. Am. Chem. Soc. 2011, 133, 1877–1884. 6. Caserta, G. et al. ChemBioChem 2018 (doi: 10.1002/cbic.201800200

A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = −0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model

Results of questionnaire for different conditions.

<p>Results of the questionnaire in the different stimulation conditions. By comparing the upper and lower panel it can be noted that the tapping conditions were overall lower rated lower than the brushstrokes conditions. Asterisks legend: * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001.</p

Experimental set-up.

<p>Experimental set-up during the modality mismatch experimental condition. A) Participants wore ear-muffs to block out any noise arising from the vibration and a skin conductance sensor on the palm of their right hand. Participants were instructed to fix their sight on the rubber hand, throughout the experiment. B) Close up on the placement of the vibrotactile units on the index and middle fingers of the participant, and on the keypad used to trigger them.</p

Results of proprioceptive drift (left) and of psychological induced sweating (right) for different conditions.

<p>Left panel. Mean proprioceptive drift (in cm) measured as a difference between the pre-stimulation and post-stimulation pointing tasks. The histogram shows data from all subjects in the different experimental conditions (* indicates p<0.05). <b>Right panel.</b> Mean psychologically induced sweating, as measured by the skin conductance response (SCR in microsiemens) after the threat stimuli on the rubber hand on all participants (N = 20), in the six different experimental conditions (* indicates p<0.05).</p

Experimental conditions.

<p>Schematic diagrams showing the six experimental conditions used to induce the Rubber Hand Illusion (RHI) in our experiments. A) Synchronous Congruent Brushstroke (SCB) was the classic RHI as designed by Botvinick and Cohen (1998). B) Asynchronous Congruent Brushstroke (ACB). C) Synchronous Incongruent Brushstroke (SIB) was our first experimental (modality mismatched) condition: brush strokes and vibrations were delivered synchronously on the rubber hand and real hand, respectively. D) Synchronous Congruent Tapping (SCT) was a modified version of RHI. E) Asynchronous Congruent Tapping (ACT). F) Synchronous Incongruent Tapping (SIT) was our second experimental condition: taps and vibrations were delivered synchronously on the rubber hand and real hand, respectively.</p