Motor imagery training to improve language processing: What are the arguments?

Studies showed that motor expertise was found to induce improvement in language processing. Grounded and situated approaches attributed this effect to an underlying automatic simulation of the motor experience elicited by action words, similar to motor imagery (MI), and suggest shared representations of action conceptualization. Interestingly, recent results also suggest that the mental simulation of action by MI training induces motor-system modifications and improves motor performance. Consequently, we hypothesize that, since MI training can induce motor-system modifications, it could be used to reinforce the functional connections between motor and language system, and could thus lead to improved language performance. Here, we explore these potential interactions by reviewing recent fundamental and clinical literature in the action-language and MI domains. We suggested that exploiting the link between action language and MI could open new avenues for complementary language improvement programs. We summarize the current literature to evaluate the rationale behind this novel training and to explore the mechanisms underlying MI and its impact on language performance.

Resting-State Functional Connectivity following Phonological Component Analysis: The Combined Action of Phonology and Visual Orthographic Cues.

Anomia is the most frequent and pervasive symptom for people with aphasia (PWA). Phonological component analysis (PCA) is a therapy incorporating phonological cues to treat anomia. Investigations of neural correlates supporting improvements following PCA remain scarce. Resting-state functional connectivity (rsFC) as a marker of therapy-induced neuroplasticity has been reported by our team. The present study explores the efficacy of PCA in French and associated therapy-induced neuroplasticity using whole-brain rsFC analysis. Ten PWA participated in a pre-/post-PCA fMRI study with cognitive linguistic assessments. PCA was delivered in French following the standard procedure. PCA led to significant improvement with trained and untrained items. PCA also led to changes in rsFC between distributed ROIs in the semantic network, visual network, and sub-cortical areas. Changes in rsFC can be interpreted within the frame of the visual and phonological nature of PCA. Behavioral and rsFC data changes associated with PCA in French highlight its efficacy and point to the importance of phonological and orthographic cues to consolidate the word-retrieval strategy, contributing to generalization to untrained words.

Increased links between language and motor areas: A proof-of-concept study on resting-state functional connectivity following Personalized Observation, Execution and Mental imagery therapy in chronic aphasia.

A tight coupling of language and motor processes has been established, which is consistent with embodied cognition theory. However, very few therapies have been designed to exploit the synergy between motor and language processes to help rehabilitate people with aphasia (PWA). Moreover, the underlying mechanisms supporting the efficacy of such approaches remain unknown. Previous work in our laboratory has demonstrated that personalized observation, execution, and mental imagery therapy (POEM)-a new therapy using three sensorimotor strategies to trigger action verb naming-leads to significant improvements in verb retrieval in PWA. Moreover, these improvements were supported by significant activations in language and sensorimotor processing areas, which further reinforce the role of both processes in language recovery (Durand et al., 2018). The present study investigates resting state functional connectivity (rsFC) changes following POEM in a pre-/post-POEM therapy design. A whole brain network functional connectivity approach was used to assess and describe changes in rsFC in a group of four PWA, who were matched and compared with four healthy controls (HC). Results showed increased rsFC in PWA within and between visuo-motor and language areas (right cuneal cortex-left supracalcarin (SCC) cortex/right precentral gyrus (PreCG)-left lingual gyrus (LG)) and between areas involved in action processing (right anterior parahippocampal gyrus (aPaHC)-left superior parietal lobule (SPL). In comparison to HC, the PWA group showed increased rsFC between the right inferior frontal gyrus (IFG) and left thalamus, which are areas involved in lexico-semantic processing. This proof-of-concept study suggests that the sensorimotor and language strategies used in POEM may induce modifications in large-scale networks, probably derived from the integration of visual and sensorimotor systems to sustain action naming, which is consistent with the embodied cognition theory.

Thermal unfolding of calreticulin. Structural and thermodynamic characterization of the transition.

Calreticulin (CRT) is a calcium-binding protein that participates in several cellular processes including the control of protein folding and homeostasis of Ca2+. Its folding, stability and functions are strongly controlled by the presence of Ca2+. The oligomerization state of CRT is also relevant for its functions. We studied the thermal transitions of monomers and oligomers of CRT by differential scanning calorimetry (DSC), circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) in the presence and absence of Ca2+. We found three and two components for the calorimetric transition in the presence and absence of Ca2+ respectively. The presence of several components was also supported by CD and FTIR spectra acquired as a function of the temperature. The difference between the heat capacity of the native and the unfolded state strongly suggests that interactions between protein domains also contribute to the heat uptake in a calorimetry experiment. We found that once unfolded at high temperature the process is reversible and the native state can be recovered upon cooling only in the absence of Ca2+. We also propose a new simple method to obtain pure CRT oligomers.

The Neural and Behavioral Correlates of Anomia Recovery following Personalized Observation, Execution, and Mental Imagery Therapy: A Proof of Concept.

The impact of sensorimotor strategies on aphasia recovery has rarely been explored. This paper reports on the efficacy of personalized observation, execution, and mental imagery (POEM) therapy, a new approach designed to integrate sensorimotor and language-based strategies to treat verb anomia, a frequent aphasia sign. Two participants with verb anomia were followed up in a pre-/posttherapy fMRI study. POEM was administered in a massed stimulation schedule, with personalized stimuli, resulting in significant improvement in both participants, with both trained and untrained items. Given that the latter finding is rarely reported in the literature, the evidence suggests that POEM favors the implementation of a word retrieval strategy that can be integrated and generalized. Changes in fMRI patterns following POEM reflect a reduction in the number of recruited areas supporting naming and the recruitment of brain areas that belong to the language and mirror neuron systems. The data provide evidence on the efficacy of POEM for verb anomia, while pointing to the added value of combined language and sensorimotor strategies for recovery from verb anomia, contributing to the consolidation of a word retrieval strategy that can be better generalized to untrained words. Future studies with a larger sample of participants are required to further explore this avenue.

Maladaptive Plasticity in Aphasia: Brain Activation Maps Underlying Verb Retrieval Errors.

Anomia, or impaired word retrieval, is the most widespread symptom of aphasia, an acquired language impairment secondary to brain damage. In the last decades, functional neuroimaging techniques have enabled studying the neural basis underlying anomia and its recovery. The present study aimed to explore maladaptive plasticity in persistent verb anomia, in three male participants with chronic nonfluent aphasia. Brain activation maps associated with semantic verb paraphasia occurring within an oral picture-naming task were identified with an event-related fMRI paradigm. These maps were compared with those obtained in our previous study examining adaptive plasticity (i.e., successful verb naming) in the same participants. The results show that activation patterns related to semantic verb paraphasia and successful verb naming comprise a number of common areas, contributing to both maladaptive and adaptive neuroplasticity mechanisms. This finding suggests that the segregation of brain areas provides only a partial view of the neural basis of verb anomia and successful verb naming. Therefore, it indicates the importance of network approaches which may better capture the complexity of maladaptive and adaptive neuroplasticity mechanisms in anomia recovery.

Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding.

Protein arginylation mediated by arginyl-tRNA protein transferase is a post-translational modification that occurs widely in biology, it has been shown to regulate protein and properties and functions. Post-translational arginylation is critical for embryogenesis, cardiovascular development and angiogenesis but the molecular effects of proteins arginylated in vivo are largely unknown. In the present study, we demonstrate that arginylation reduces CRT (calreticulin) thermostability and induces a greater degree of dimerization and oligomerization. R-CRT (arginylated calreticulin) forms disulfide-bridged dimers that are increased in low Ca(2+) conditions at physiological temperatures, a similar condition to the cellular environment that it required for arginylation of CRT. Moreover, R-CRT self-oligomerizes through non-covalent interactions that are enhanced at temperatures above 40 °C, condition that mimics the heat shock treatment where R-CRT is the only isoespecies of CRT that associates in cells to SGs (stress granules). We show that in cells lacking CRT the scaffolding of larger SGs is impaired; the transfection with CRT (hence R-CRT expression) restores SGs assembly whereas the transfection with CRT mutated in Cys146 does not. Thus, R-CRT disulfide-bridged dimers (through Cys146) are essential for the scaffolding of larger SGs under heat shock, although these dimers are not required for R-CRT association to SGs. The alteration in SGs assembly is critical for the normal cellular recover of cells after heat induced stress. We conclude that R-CRT is emerging as a novel protein that has an impact on the regulation of SGs scaffolding and cell survival.

Galectin-1 confers immune privilege to human trophoblast: implications in recurrent fetal loss.

Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies.

De novo 15q21.1q21.2 deletion identified through FBN1 MLPA and refined by 244K array-CGH in a female teenager with incomplete Marfan syndrome.

Interstitial deletions involving the 15q21.1 band are very rare. Only 4 of these cases have been studied using molecular cytogenetic techniques in order to confirm the deletion of the whole FBN1 gene. The presence of clinical features of the Marfan syndrome (MFS) spectrum associated with mental retardation has been described in only 2/4 patients. Here we report on a 16-year-old female referred for suspicion of MFS (positive thumb and wrist sign, scoliosis, joint hyperlaxity, high-arched palate with dental crowding, dysmorphism, mitral insufficiency with dystrophic valve, striae). She had therefore 3 minor criteria according to the Ghent nosology. She also had speech disabilities but could follow normal school training. Direct sequencing of the FBN1, TGFBR1 and TGFBR2 genes was negative. MLPA revealed a genomic deletion of the whole FBN1 gene, confirmed by loss of heterozygosity of maternal alleles for several microsatellite markers surrounding the FBN1 gene. The deletion was confirmed by FISH using a FBN1 probe and was not found in the parents. Array-CGH permitted to define a 2.97 Mb deletion, which was the smallest 15q microdeletion including FBN1. Contrary to the other published observations, our proband does not exhibit mental retardation, but neuropsychological evaluations revealed an attention deficit as well as a deficit in information-processing speed. Haploinsufficiency of FBN1 is likely to contribute to the presence of MFS features. However, attenuated features could be explained because disturbances of TGF-beta signalling associated with FBN1 mutations do not exert full phenotypic effect through simple haploinsufficiency. Phenotypic variability in other patients with interstitial deletions including 15q21.1 band may reflect differences in deletion size and/or cys/trans modifying factors.

The arginylation-dependent association of calreticulin with stress granules is regulated by calcium.

Post-translational modifications of proteins are important for the regulation of cell functions; one of these modifications is post-translational arginylation. In the present study, we show that cytoplasmic CRT (calreticulin) is arginylated by ATE1 (arginyl-tRNA protein transferase). We also show that a pool of CRT undergoes retrotranslocation from the ER (endoplasmic reticulum) to the cytosol, because in CRT-knockout cells transfected with full-length CRT (that has the signal peptide), cytoplasmic CRT appears as a consequence of its expression and processing in the ER. After the cleavage of the signal peptide, an N-terminal arginylatable residue is revealed prior to retrotranslocation to the cytoplasm where arginylation takes place. SGs (stress granules) from ATE1-knockout cells do not contain CRT, indicating that CRT arginylation is required for its association to SGs. Furthermore, R-CRT (arginylated CRT) in the cytoplasm associates with SGs in cells treated with several stressors that lead to a reduction of intracellular Ca2+ levels. However, in the presence of stressors that do not affect Ca2+ levels, R-CRT is not recruited to these loci despite the fact that SGs are formed, demonstrating Ca2+-dependent R-CRT association to SGs. We conclude that post-translational arginylation of retrotranslocated CRT, together with the decrease in intracellular Ca2+, promotes the association of CRT to SGs.

Association of maternal obesity and childhood obesity: implications for healthcare providers.

The purpose of this critical appraisal was to assess the available literature on the association of maternal obesity as a risk factor for childhood obesity and to explore the implications for incorporating this evidence into practice. The increasing prevalence of childhood obesity, with its documented adverse health effects, is a critical public health threat in the United States and worldwide. Research studies have documented increased rates of childhood obesity associated with maternal obesity. Healthcare providers are challenged to expand their competencies to recognize the association of maternal obesity and childhood obesity and to address both primary and secondary prevention of childhood obesity. Stopping the cycle of obesity before it becomes the leading cause of preventable disease and death in the United States is a priority for community health nurses.