Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors

Background: A conventional treatment outcome is suboptimal for sensory impairments in stroke patients. Novel approaches based on electrical stimulation or robotics are proposed as an adjuvant for rehabilitation, though their efficacy for motor, sensory, and body representation recovery have not been tested. Methods: Sixty chronic stroke patients with unilateral motor deficits were included in a pseudo-randomized open-label multi-arm control trial (ClinicalTrials.gov: NCT03349138). We tested the effects of a robotic glove (GloReha [GR]) and a new neuromuscular electrical stimulation system (Helping Hand [HH]) and compared them with conventional treatment (CT) in restoring motor and sensory functions and the affected limb perception. HH was designed to concurrently deliver peripheral motor activation and enhanced cutaneous sensation. Patients were split in four dose-matched groups: CT, GR, HH, and GRHH (receiving 50% GR and 50% HH). Assessments were performed at inclusion, halfway, end of treatment (week 9), and follow-up (week 13). Findings: HH provided an earlier benefit, quantified by the Motricity Index (MI), than GR. At the end of the treatment, the amelioration was higher in groups GRHH and HH and extended to somatosensory functions. These benefits persisted at the follow-up. GRHH and HH also improved the perceived dimensions and altered feeling toward the affected limb. Interestingly, the reduction of altered feelings correlated with MI improvements and depended on the amount of HH. Conclusions: We suggest that HH concurrently stimulates sensory and motor systems by generating an enhanced cutaneous sensation, coherent in location with the elicited motor recruitment, leading to ameliorated sensorimotor functions and bodily perceptions in stroke patients. Funding: This work was supported by a Foundation advised by CARIGEST, by Fondazione CARIPLO, by the SNSF NCCR Robotics, and by the Bertarelli Foundation

Two-Dimensional Impulsively Stimulated Resonant Raman Spectroscopy of Molecular Excited States

Monitoring the interactions between electronic and vibrational degrees of freedom in molecules is critical to our understanding of their structural dynamics. This is typically hampered by the lack of spectroscopic probes able to detect different energy scales with high temporal and frequency resolution. Coherent Raman spectroscopy can combine the capabilities of multidimensional spectroscopy with structural sensitivity at ultrafast timescales. Here, we develop a three-color-based 2D impulsive stimulated Raman technique that can selectively probe vibrational mode couplings between different active sites in molecules by taking advantage of resonance Raman enhancement. Three temporally delayed pulses generate nuclear wave packets whose evolution reports on the underlying potential energy surface, which we decipher using a diagrammatic approach enabling us to assign the origin of the spectroscopic signatures. We benchmark the method by revealing vibronic couplings in the ultrafast dynamics following photoexcitation of the green fluorescent protein

Two-Dimensional Impulsively Stimulated Resonant Raman Spectroscopy of Molecular Excited States

Monitoring the interactions between electronic and vibrational degrees of freedom in molecules is critical to our understanding of their structural dynamics. This is typically hampered by the lack of spectroscopic probes able to detect different energy scales with high temporal and frequency resolution. Coherent Raman spectroscopy can combine the capabilities of multidimensional spectroscopy with structural sensitivity at ultrafast timescales. Here, we develop a three-color-based 2D impulsive stimulated Raman technique that can selectively probe vibrational mode couplings between different active sites in molecules by taking advantage of resonance Raman enhancement. Three temporally delayed pulses generate nuclear wave packets whose evolution reports on the underlying potential energy surface, which we decipher using a diagrammatic approach enabling us to assign the origin of the spectroscopic signatures. We benchmark the method by revealing vibronic couplings in the ultrafast dynamics following photoexcitation of the green fluorescent protein.C. S. acknowledges financial support by the Royal Commission for the Exhibition of 1851. G. Bat. acknowledges the “Avvio Alla Ricerca 2018” grant by Sapienza Universitá di Roma. T. W. acknowledges the Marie Curie Intra-European Fellowship (PIEF-GA-2013-623651) within the 7th European Community Framework Programme. S. M. gratefully acknowledges the support of the National Science Foundation Grant No. CHE-1663822

Analysis of sequence variability and transcriptional profile of cannabinoid synthase genes in cannabis sativa l. Chemotypes with a focus on cannabichromenic acid synthase

Cannabis sativa L. has been long cultivated for its narcotic potential due to the accumulation of tetrahydrocannabinolic acid (THCA) in female inflorescences, but nowadays its production for fiber, seeds, edible oil and bioactive compounds has spread throughout the world. However, some hemp varieties still accumulate traces of residual THCA close to the 0.20% limit set by European Union, despite the functional gene encoding for THCA synthase (THCAS) is lacking. Even if some hypotheses have been produced, studies are often in disagreement especially on the role of the cannabichromenic acid synthase (CBCAS). In this work a set of European Cannabis genotypes, representative of all chemotypes, were investigated from a chemical and molecular point of view. Highly specific primer pairs were developed to allow an accurate distinction of different cannabinoid synthases genes. In addition to their use as markers to detect the presence of CBCAS at genomic level, they allowed the analysis of transcriptional profiles in hemp or marijuana plants. While the high level of transcription of THCAS and cannabidiolic acid synthase (CBDAS) clearly reflects the chemical phenotype of the plants, the low but stable transcriptional level of CBCAS in all genotypes suggests that these genes are active and might contribute to the final amount of cannabinoids

Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6–12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI–FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways

Identification of a new R3 MYB type repressor and functional characterization of the members of the MBW transcriptional complex involved in anthocyanin biosynthesis in eggplant (S. Melongena L.)

Here we focus on the highly conserved MYB-bHLH-WD repeat (MBW) transcriptional complex model in eggplant, which is pivotal in the transcriptional regulation of the anthocyanin biosynthetic pathway. Through a genome-wide approach performed on the recently released Eggplant Genome (cv. 67/3) previously identified, and reconfirmed by us, members belonging to the MBW complex (SmelANT1, SmelAN2, SmelJAF13, SmelAN1) were functionally characterized. Furthermore, a regulatory R3 MYB type repressor (SmelMYBL1), never reported before, was identified and characterized as well. Through a qPCR approach, we revealed specific transcriptional patterns of candidate genes in different plant tissue/organs at two stages of fruit development. Two strategies were adopted for investigating the interactions of bHLH partners (SmelAN1, SmelJAF13) with MYB counterparts (SmelANT1, SmelAN2 and SmelMYBL1): Yeast Two Hybrid (Y2H) and Bimolecular Fluorescent Complementation (BiFC) in A. thaliana mesophylls protoplast. Agro-infiltration experiments highlighted that N. benthamiana leaves transiently expressing SmelANT1 and SmelAN2 showed an anthocyanin-pigmented phenotype, while their co-expression with SmelMYBL1 prevented anthocyanin accumulation. Our results suggest that SmelMYBL1 may inhibits the MBW complex via the competition with MYB activators for bHLH binding site, although this hypothesis requires further elucidation

A chromosome-anchored eggplant genome sequence reveals key events in Solanaceae evolution

With approximately 450 species, spiny Solanum species constitute the largest monophyletic group in the Solanaceae family, but a high-quality genome assembly from this group is presently missing. We obtained a chromosome-anchored genome assembly of eggplant (Solanum melongena), containing 34,916 genes, confirming that the diploid gene number in the Solanaceae is around 35,000. Comparative genomic studies with tomato (S. lycopersicum), potato (S. tuberosum) and pepper (Capsicum annuum) highlighted the rapid evolution of miRNA:mRNA regulatory pairs and R-type defense genes in the Solanaceae, and provided a genomic basis for the lack of steroidal glycoalkaloid compounds in the Capsicum genus. Using parsimony methods, we reconstructed the putative chromosomal complements of the key founders of the main Solanaceae clades and the rearrangements that led to the karyotypes of extant species and their ancestors. From 10% to 15% of the genes present in the four genomes were syntenic paralogs (ohnologs) generated by the pre-γ, γ and T paleopolyploidy events, and were enriched in transcription factors. Our data suggest that the basic gene network controlling fruit ripening is conserved in different Solanaceae clades, and that climacteric fruit ripening involves a differential regulation of relatively few components of this network, including CNR and ethylene biosynthetic genes

Different tool training induces specific effects on body metric representation

Morphology and functional aspects of the tool have been proposed to be critical factors modulating tool use-induced plasticity. However, how these aspects contribute to changing body representation has been underinvestigated. In the arm bisection task, participants have to estimate the length of their own arm by indicating its midpoint, a paradigm used to investigate the representation of the metric properties of the body. We employed this paradigm to investigate the impact of different actions onto tool embodiment. Our findings suggest that a training requiring actions mostly with proximal (shoulder) or distal (wrist) parts induces a different shift in the perceived arm midpoint. This effect is independent of, but enhanced by, the use of the tool during the training and in part influenced by specific demands of the task. These results suggest that specific motor patterns required by the training can induce different changes of body representation, calling for rethinking the concept of tool embodiment, which would be characterized not simply by the morphology of the tools, but also by the actions required for their specific use

Spatial limits of visuotactile interactions in the presence and absence of tactile stimulation

The presence of a light flash near to the body not only increases the ability to detect a weak touch but also increases reports of feeling a weak touch that did not occur. The somatic signal detection task (SSDT) provides a behavioural marker by which to clarify the spatial extent of such visuotactile interactions in peripersonal space. Whilst previous evidence suggests a limit to the spatial extent over which visual input can distort the perception of tactile stimulation during the rubber hand illusion, the spatial boundaries of light-induced tactile sensations are not known. In a repeated measures design, 41 participants completed the SSDT with the light positioned 1 cm (near), 17.5 cm (mid) or 40 cm (far) from the tactile stimulation. In the far condition, the light did not affect hit, or false alarm rates during the SSDT. In the near and mid conditions, the light significantly increased hit rates and led to a more liberal response criterion, that is, participants reported feeling the touch more often regardless of whether or not it actually occurred. Our results demonstrate a spatial boundary over which visual input influences veridical and non-veridical touch perception during the SSDT, and provide further behavioural evidence to show that the boundaries of the receptive fields of visuotactile neurons may be limited to reach space