Toward individualized medicine in stroke-The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke.

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.

Biofeedback training for partial weight bearing in patients after total hip arthroplasty.

OBJECTIVE: To evaluate a new biofeedback training method based on visual delivery of information in patients after total hip arthroplasty (THA). DESIGN: Intervention study with prepost design. SETTING: Hospitalized care in a university referral center. PARTICIPANTS: Patients (N=11) (age 56.1+/-9.0 y) shortly after THA. INTERVENTION: A mobile system has been used for biofeedback training with the predefined partial weight bearing (PWB) threshold of 20 kg. After the learning period, 4 retention tests, consisting of 3 successive walking cycles without feedback, were recorded for each patient: (1) acquisition test, (2) early retention test (after 30 min), (3) the day after, and (4) after 2 days. MAIN OUTCOME MEASURE: The pressure error and the maximum pressure force at each step before and after biofeedback training. RESULTS: A significant difference of pressure errors between the beginning and the end of the learning period has been measured (42.5+/-22.5 N vs 3.7+/-11.4N, P<.001). However, there was no difference between the beginning of the learning period and different retention tests (after 30 minutes, after 1 day, after 2 days). In terms of maximal pressure force, there was a difference between the beginning and the end of learning (251 N vs 195 N, P<.05). The retention tests did not show significant differences compared with the baseline values. CONCLUSIONS: THA patients were able to use the defined PWB during a short period of time and shortly after stopping the training; both the pressure errors and the maximal pressure force attended the values before training. These results confirm the difficulties to achieve PWB in patients after THA.

The Impact of Language Opacity and Proficiency on Reading Strategies in Bilinguals: An Eye Movement Study.

Reading strategies vary across languages according to orthographic depth - the complexity of the grapheme in relation to phoneme conversion rules - notably at the level of eye movement patterns. We recently demonstrated that a group of early bilinguals, who learned both languages equally under the age of seven, presented a first fixation location (FFL) closer to the beginning of words when reading in German as compared with French. Since German is known to be orthographically more transparent than French, this suggested that different strategies were being engaged depending on the orthographic depth of the used language. Opaque languages induce a global reading strategy, and transparent languages force a local/serial strategy. Thus, pseudo-words were processed using a local strategy in both languages, suggesting that the link between word forms and their lexical representation may also play a role in selecting a specific strategy. In order to test whether corresponding effects appear in late bilinguals with low proficiency in their second language (L2), we present a new study in which we recorded eye movements while two groups of late German-French and French-German bilinguals read aloud isolated French and German words and pseudo-words. Since, a transparent reading strategy is local and serial, with a high number of fixations per stimuli, and the level of the bilingual participants' L2 is low, the impact of language opacity should be observed in L1. We therefore predicted a global reading strategy if the bilinguals' L1 was French (FFL close to the middle of the stimuli with fewer fixations per stimuli) and a local and serial reading strategy if it was German. Thus, the L2 of each group, as well as pseudo-words, should also require a local and serial reading strategy. Our results confirmed these hypotheses, suggesting that global word processing is only achieved by bilinguals with an opaque L1 when reading in an opaque language; the low level in the L2 gives way to a local and serial reading strategy. These findings stress the fact that reading behavior is influenced not only by the linguistic mode but also by top-down factors, such as readers' proficiency.

Balanced bilinguals favor lexical processing in their opaque language and conversion system in their shallow language.

Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280 ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography.

Language context modulates reading route: an electrical neuroimaging study.

INTRODUCTION: The orthographic depth hypothesis (Katz and Feldman, 1983) posits that different reading routes are engaged depending on the type of grapheme/phoneme correspondence of the language being read. Shallow orthographies with consistent grapheme/phoneme correspondences favor encoding via non-lexical pathways, where each grapheme is sequentially mapped to its corresponding phoneme. In contrast, deep orthographies with inconsistent grapheme/phoneme correspondences favor lexical pathways, where phonemes are retrieved from specialized memory structures. This hypothesis, however, lacks compelling empirical support. The aim of the present study was to investigate the impact of orthographic depth on reading route selection using a within-subject design. METHOD: We presented the same pseudowords (PWs) to highly proficient bilinguals and manipulated the orthographic depth of PW reading by embedding them among two separated German or French language contexts, implicating respectively, shallow or deep orthography. High density electroencephalography was recorded during the task. RESULTS: The topography of the ERPs to identical PWs differed 300-360 ms post-stimulus onset when the PWs were read in different orthographic depth context, indicating distinct brain networks engaged in reading during this time window. The brain sources underlying these topographic effects were located within left inferior frontal (German > French), parietal (French > German) and cingular areas (German > French). CONCLUSION: Reading in a shallow context favors non-lexical pathways, reflected in a stronger engagement of frontal phonological areas in the shallow versus the deep orthographic context. In contrast, reading PW in a deep orthographic context recruits less routine non-lexical pathways, reflected in a stronger engagement of visuo-attentional parietal areas in the deep versus shallow orthographic context. These collective results support a modulation of reading route by orthographic depth.