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The ipsilateral hand (ILH) is impaired after unilateral stroke, but the underlying mechanisms remain unresolved. Based on the degeneracy theory of network connectivity that many connectivity patterns are functionally equivalent, we hypothesized that ILH impairment would result from the summation of microstructural white matter (WM) disruption in the motor network, with a task-related profile. We aimed to determine the WM disruption patterns associated with ILH impairment.This was a cross-sectional analysis of patients in the ISIS-HERMES Study with ILH and diffusion-MRI data collected 1 month post-stroke. Patients performed three tasks, the Purdue Pegboard Test (PPT), handgrip strength, and movement time. Fractional anisotropy (FA) derived from diffusion MRI was measured in 33 WM regions. We used linear regression models controlling for age, sex, and education to determine WM regions associated with ILH impairment.PPT was impaired in 42%, grip in 59%, and movement time in 24% of 29 included patients (mean age, 51.9 ± 10.5 years; 21 men). PPT was predicted by ipsilesional corticospinal tract (i-CST) (B = 17.95; p = 0.002) and superior longitudinal Fasciculus (i-SLF) (B = 20.52; p = 0.008); handgrip by i-CST (B = 109.58; p = 0.016) and contralesional anterior corona radiata (B = 42.69; p = 0.039); and movement time by the corpus callosum (B = - 1810.03; p = 0.003) i-SLF (B = - 917.45; p = 0.015), contralesional pons-CST (B = 1744.31; p = 0.016), and i-corticoreticulospinal pathway (B = - 380.54; p = 0.037).ILH impairment was associated with WM disruption to a combination of ipsilateral and contralesional tracts with a pattern influenced by task-related processes, supporting the degeneracy theory. We propose to integrate ILH assessment in rehabilitation programs and treatment interventions such as neuromodulation.

Ipsilateral hand (ILH) impairment is documented following motor stroke, but its impact on long-term outcome remains unknown. We assessed ILH impairment in subacute stroke and tested whether ILH impairment predicted long-term outcome.We performed a longitudinal study in 209 consecutive patients with unilateral stroke and sensorimotor deficit at admission. ILH impairment was evaluated using the Purdue Pegboard Test (PPT) and handgrip strength and defined as mild (z-score -1) or moderate (z-score -1.65). We used logistic regression (LR) to predict outcome assessed 9 (range, 7-12) months post-stroke with the modified Rankin scale (mRS) categorized into good (mRS ≤ 1) and poor outcome (mRS ≥ 2). For internal validation, LR-bootstrapping and cross-validation with LASSO and Random Forest were performed.ILH impairment assessed at 89.04 ± 45.82 days post-stroke was moderate in 10.53% (95% CI 6.7, 14.83) for PPT and 17.22% (95% CI 11.96, 22.49) for grip, and mild in 21.05% (95% CI 15.78, 26.79) for PPT and 35.89 (95% CI 29.67, 42.58) for grip. Good outcome was predicted by ILH-PPT (B = 1.03 [95% CI 0.39, 3.31]), ILH-grip (B = 1.16 [95% CI 0.54, 3.53]), low NIHSS-discharge (B = -1.57 [95% CI -4.0, -1.19]), and no depression (B = -0.62 [95% CI -1.63, -0.43]), accounting for stroke delay (B = -0.011 [95% CI -0.06, 0.01]). Model efficiency was 91.6% (AUC = 0.977; 95% CI 0.959, 0.996). LASSO and Random Forest methods provided similar results, confirming the LR model robustness.ILH impairment is frequent after motor stroke and predicts long-term outcome. We propose to integrate ILH impairment into rehabilitation programs to improve recovery and serve research interventions such as neuromodulation.

Motor hand deficits impact autonomy in everyday life, and neuroplasticity processes of motor recovery can be explored using functional MRI (fMRI). However, few studies have used fMRI to explore the mechanisms underlying hand recovery following stroke. Based on the dual visuomotor model positing that two segregated dorsomedial and dorsolateral cerebral networks control reach and grasp movements, we explored the relationship between motor task-related activity in the sensorimotor network and hand recovery following stroke. Behavioral recovery was explored with a handgrip force task assessing simple grasp, and a visuomotor reaching and precise grasping task, the Purdue Pegboard Test (PPT). We used a passive wrist flexion-extension task to measure fMRI activity in 36 sensorimotor brain areas. Behavioral and fMRI measurements were performed in 27 patients (53.2 ± 9.5 years) 1-month following stroke, and then 6-month and 24-month later. The effects of sensorimotor activity on hand recovery were analyzed using correlations and linear mixed models (LMMs). PPT and handgrip force correlated with fMRI activity measures in the sensorimotor and parietal areas. PPT recovery was modeled by fMRI measures in the ipsilesional primary motor cortex (MI-4p), superior parietal lobule (SPL-7M) and parietal operculum OP1, and lesion side. Handgrip force was modeled by ipsilesional MI-4a, OP1, and contralesional inferior parietal lobule (IPL-PFt). Moreover, the relationship between fMRI activity and hand recovery was time-dependent, occurring in the early recovery period in SPL-BA-7M, and later in MI. These results suggest that areas of both dorsolateral and dorsomedial networks participate to visuomotor reach and grasp tasks (PPT), while dorsolateral network areas may control recovery of simple grasp (handgrip force), suggesting that the type of movement modulates network recruitment. We also found functional dissociations between MI-4p related to PPT that required independent finger movements and MI-4a related to simple grasp without independent finger movements. These findings need to be replicated in further studies.

ObjectiveTo identify candidate biomarkers of walking recovery with motor tract integrity measurements using fractional anisotropy (FA) from the corticospinal tract (CST) and alternative motor pathways in patients with moderate to severe subacute stroke.MethodsWalking recovery was first assessed with generalized linear mixed model (GLMM) with repeated measures of walking scores (WS) over 2 years of follow-up in a longitudinal study of 29 patients with subacute ischemic stroke. Baseline FA measures from the ipsilesional and contralesional CST (i-CST and c-CST), cortico-reticulospinal pathway (i-CRP and c-CRP), and cerebellar peduncles were derived from a 60-direction diffusion MRI sequence on a 3T scanner. We performed correlation tests between WS and FA measures. Third, we investigated using GLMM whether motor tract integrity contributes to predict walking recovery.ResultsWe observed significant improvements of WS over time with a plateau reached at ≈6 months after stroke. WS significantly correlated with FA measures from i-CST, c-CST, i-CRP, and bilateral cerebellar peduncles. Walking recovery was predicted by FA measures from 3 tracts: i-CST, i-CRP, and contralesional superior cerebellar peduncle (c-SCP). Diffusion tensor imaging (DTI) predictors captured 80.5% of the unexplained variance of the model without DTI.ConclusionsWe identified i-CST and alternative motor-related tracts (namely i-CRP and c-SCP) as candidate biomarkers of walking recovery. The role of the SCP in walk recovery may rely on cerebellar nuclei projections to the thalamus, red nucleus, and reticular formation. Our findings suggest that a set of white matter tracts, part of subcortical motor networks, contribute to walking recovery in patients with moderate to severe stroke.

Although less-affected hand (LAH) deficits following unilateral stroke are well documented, many aspects of LAH impairment mechanisms remain unresolved. To provide a better understanding of these mechanisms, we used diffusion MRI to examine the disruptions of white matter structural connections. Based on the redundancy theory, we hypothesized that a summation of motor-related tract disruptions would characterize LAH impairment. We assessed LAH impairment and fractional anisotropy (FA) in 28 patients at one-month post-stroke (baseline), and 6 and 24 months later. LAH impairment was assessed with the Purdue Pegboard Test (PPT), handgrip strength, and movement time. FA was estimated in the CST, Anterior- Corona Radiata (ACR), and Limb of Internal Capsule (ALIC), Superior Longitudinal Fasciculus (SLF), and corpus callosum (CC). We used Linear Mixed Models to determine the tracts associated with LAH impairment over time. Baseline PPT, grip, and movement time were impaired in 43%, 61%, and 25%, respectively. PPT was modeled by baseline ipsilesional-CST (t=3.75; p

Lacunar stroke is a common subtype of stroke, comprising 20%–25% of ischemic strokes, linking a number of clinical syndromes to occlusion of a single perforating artery (40–900 μm in diameter) resulting from vasculopathy characterized by lipohyalinosis, arteriolosclerosis, and microatheroma. Hypertension is the leading cause, along with atherosclerosis and other stroke risk factors.1-3 Lacunes may be described as small deep cerebral infarcts, 3–17 mm in maximum diameter, located in cerebral hemisphere and brainstem regions supplied by perforating arteries.4 The term lacune stems from the French literature in the 19th century to describe, based on anatomical examination, small cavities with liquefaction necrosis.

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Background: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods: A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results: Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

Apraxia, a cognitive disorder of motor control, can severely impair transitive actions (object-related) and may lead to action errors (e.g., rubbing a hammer on a nail instead of pounding it) and hand posture errors (e.g., grasping a tool in a wrong way). Here, we report a rare observation of a left-handed patient, left-lateralized for language, who developed a severe apraxia following a right brain lesion. Interestingly the patient showed a significant number of hand posture errors, while she perfectly demonstrated the actual use of tools. This case stressed the predictions made by the current theories of tool use. According to the manipulation-based approach, the hand posture errors should be associated with an impaired manipulation knowledge. According to the reasoning-based approach, the absence of action errors should be associated with spared mechanical knowledge. Moreover, to better understand the neurocognitive origins of the deficit observed in VF, we examined several potential brain lateralization of praxis functions. We initiated a systematic examination of VF's performance in several contexts of tool use allowing us to investigate which kinds of tool-use representations were potentially impaired in VF. Our investigation did not reveal any major deficit of manipulation knowledge. This can hardly account for the high frequency of hand posture errors, contrary to the predictions of the manipulation-based approach. In contrast, in line with the reasoning-based approach, mechanical knowledge was spared and can explain the absence of action errors. We also found that VF probably had a bilateral organization of praxis functions, but irrespective of the possible brain lateralization considered, none of which established a satisfactory association between manipulation knowledge and hand posture errors. Taken together, the manipulation-based approach fails to explain fully the deficit presented by this patient and should lead us to consider alternative explanations.

Background Cell therapy is promising in experimental studies and has been assessed only in a few studies on humans. Aims To evaluate the effect of cell therapy in humans. Methods We included clinical trials with a control group that reported safety and efficacy six months following treatment. Quality was evaluated and clinical scales data were extracted. Quantitative analysis was based on the standardized means difference (SMD). Among 28 trials published from 1995 to 2016, nine studies (194 patients; 191 controls) were eligible. Publication biases were assessed with the funnel plot and pre-specified explanatory variables were tested with a group analysis and a meta-regression. Results The overall quality was moderate. Cell therapy had a positive effect on the outcome (SMD: 0.57, 95% CI: 0.22–0.92; p = 0.002). The sensitivity analysis showed an upper level of effect size of 0.81 (95% CI: 0.34–1.27; p = 0.001) and a lower level of 0.455 (95% CI: 0.04–0.87; p = 0.03). None of the pre-specified explanatory variable was significantly correlated to outcome: age, ratio infarction/hemorrhage, delay from stroke to treatment, route of administration, cell type, randomization, and blinded outcome assessment. The significant heterogeneity (p = 0.03) was not explained by publication biases (p = 0.09) and was more likely due to methodological and quality differences between the trials. Conclusions This result suggests that cell therapy is beneficial in stroke and is expected to help in the designing of stem cells controlled clinical trials (CCT) in large populations.

While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later. Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation. During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p, Highlights • Motor recovery after stroke can be robustly predicted using a passive task fMRI paradigm. • Sensorimotor network activity is decreased in moderate to severe stroke patients relative to healthy controls • Compensatory mechanisms in severe stroke involve both the dorsal (MI BA4a), and the ventral (OP1 and OP4) sensorimotor stream

International audience; We evaluated the effect of normal aging on the inter-hemispheric processing of semantic information by using the divided visual field (DVF) method, with words and pictures. Two main theoretical models have been considered, (a) the HAROLD model which posits that aging is associated with supplementary recruitment of the right hemisphere (RH) and decreased hemispheric specialization, and (b) the RH decline theory, which assumes that the RH becomes less efficient with aging, associated with increased LH specialization. Two groups of subjects were examined, a Young Group (YG) and an Old Group (OG), while participants performed a semantic categorization task (living vs. non-living) in words and pictures. The DVF was realized in two steps: (a) unilateral DVF presentation with stimuli presented separately in each visual field, left or right, allowing for their initial processing by only one hemisphere, right or left, respectively; (b) bilateral DVF presentation (BVF) with stimuli presented simultaneously in both visual fields, followed by their processing by both hemispheres. These two types of presentation permitted the evaluation of two main characteristics of the inter-hemispheric processing of information, the hemispheric specialization (HS) and the inter-hemispheric cooperation (IHC). Moreover, the BVF allowed determining the driver-hemisphere for processing information presented in BVF. Results obtained in OG indicated that: (a) semantic categorization was performed as accurately as YG, even if more slowly, (b) a non-semantic RH decline was observed, and (c) the LH controls the semantic processing during the BVF, suggesting an increased role of the LH in aging. However, despite the stronger involvement of the LH in OG, the RH is not completely devoid of semantic abilities. As discussed in the paper, neither the HAROLD nor the RH decline does fully explain this pattern of results. We rather suggest that the effect of aging on the hemispheric specialization and inter-hemispheric cooperation during semantic processing is explained not by only one model, but by an interaction between several complementary mechanisms and models.

Tinnitus mechanisms remain poorly understood. Our previous functional MRI (fMRI) studies demonstrated an abnormal hyperactivity in the right parietal operculum 3 (OP3) in acoustic trauma tinnitus and during provoked phantom sound perceptions without hearing loss, which lead us to propose a new model of tinnitus. This new model is not directly linked with hearing loss and primary auditory cortex abnormalities, but with a proprioceptive disturbance related to middle-ear muscles. In the present study, a seed-based resting-state functional MRI method was used to explore the potential abnormal connectivity of this opercular region between an acoustic trauma tinnitus group presenting slight to mild tinnitus and a control group. Primary auditory cortex seeds were also explored because they were thought to be directly involved in tinnitus in most current models. In such a model, hearing loss and tinnitus handicap were confounding factors and were therefore regressed in our analysis. Between-groups comparisons showed a significant specific connectivity between the right OP3 seeds and the potential human homologue of the premotor ear-eye field (H-PEEF) bilaterally and the inferior parietal lobule (IPL) in the tinnitus group. Our findings suggest the existence of a simultaneous premotor ear-eye disturbance in tinnitus that could lift the veil on unexplained subclinical abnormalities in oculomotor tests found in tinnitus patients with normal vestibular responses. The present work confirms the involvement of the OP3 subregion in acoustic trauma tinnitus and provides some new clues to explain its putative mechanisms.

Recent studies on speech rehabilitation in aphasic patients show that a visual articulatory input can be useful for speech recovery, alongside the auditory input conventionally used. Moreover, the persistence of disorders, despite speech-therapy training generally undergone by these patients, emphasizes the need to develop new methods of speech rehabilitation. In this study, we evaluated a method of rehabilitation based on perceptual motor integration (PMI) – via the Ultraspeech player software – in two patients with chronic non-fluent aphasia after stroke. P1 showed a clinical picture of Broca’s aphasia, while P2 presented a global aphasia after stroke, which later transformed into a Broca’s aphasia. The Ultraspeech player software allows the visualization by the patient of reference tongue movements using ultrasound and video imaging for phonemes. The evaluation of the effect of this method was based on the comparison, before and after reeducation, of multimodal data allowing: a quantitative analysis of the acoustic parameters of the speech signal, a qualitative analysis of language performances and language scores, and a neurophysiological assessment of the anatomo-functional networks recruited in several language tasks. Our results show the efficiency of PMI in P1 but only a limited benefit in P2. In qualitative terms, naming, reading, word repetition, and rhyme detection improved in P1, while P2 declined in reading and rhyme detection. Quantitatively speaking, P1 improved in her production of vowels and consonants whereas P2 only partially improved in the quality of some consonants and vowels. In terms of cerebral correlates, in P1, we observed a modulation of the cerebral activity in language networks, in agreement with the behavioral improvement in speech and language, as well as efficient functional reorganization patterns. We discuss these results in the framework of theoretical models of speech motor control and we describe the conditions of PMI application in patients with non-fluent aphasia., Des études portant sur la rééducation de la parole chez des patients aphasiques montrent que l’ajout d’un support visuel, en complément du support auditif utilisé classiquement, peut être utile pour la récupération de la parole. Nous avons évalué une méthode de rééducation basée sur l’intégration perceptivo-motrice (IPM) via le logiciel Ultraspeech player, chez deux patientes présentant une aphasie non fluente chronique post-accident vasculaire cérébral (AVC). L’évaluation de l’effet de cette méthode s’est appuyée sur la comparaison, avant et après rééducation, de données multimodales permettant : une évaluation quantitative des paramètres acoustiques du signal de parole, une évaluation qualitative des performances langagières et scores de langage, et une évaluation neurophysiologique des réseaux recrutés dans des tâches langagières. Nos résultats montrent l’efficacité de l’IPM chez P1 mais un bénéfice limité chez P2. Qualitativement, la dénomination, la lecture, la répétition des mots et le jugement de rimes s’améliorent chez P1, tandis que P2 décline en lecture et jugement de rimes. Quantitativement, P1 améliore sa production de voyelles et consonnes alors que P2 s’améliore pour quelques consonnes et voyelles uniquement. En IRMf, nous observons, chez P1, une modulation de l’activité des réseaux langagiers, en accord avec l’amélioration comportementale du langage ainsi que des patrons de réorganisation fonctionnelle efficaces.

International audience; In this dynamic causal modeling (DCM) study, we evaluated the effect of age on the effective connectivity of a cerebral network involved in lexical production. Younger and older adults performed an object naming task during fMRI. The DCM was used to explore the interactions between four regions of interest: the occipital cortex, OC; the lateral temporal cortex, LTC; the medial temporal cortex, MTC; and the inferior frontal cortex, IFC. We mainly focused on the modulation of the fronto-temporal interaction, according to the hypothesis that aging requires strategies that modulate the access to the semantic knowledge, either through a neural reserve mechanism (increased MTC-LTC connectivity) or through a neural compensation mechanism (supplementary IFC-MTC connectivity). For younger adults, our results indicated a bi-directional interaction between the left IFC and LTC suggesting a typical activation related to lexico-semantic representations. For older adults, our results reveal the existence of bi-directional interaction between the IFC and MTC, but not between the IFC and LTC – which in turn suggests that older adults adapt a new strategy, via supplemental access to conceptual access and semantic retrieval processes. This neural compensation strategy would be facilitated by a top-down mechanism from the IFC to the MTC. We discuss our results in the context of the possible additional strategies used by older compared to younger adults, to retrieve and produce words.

Environmental factors contribute to the constitution and maintenance of the cognitive reserve and partially explain the variability of cognitive performance in older individuals. We assessed the role of leisure activities - social and individual - on the access to lexico-semantic representations evaluated through a task of object naming (ON). We hypothesize that compared to individual, social leisure activities explain better the ON performance in the older adults, which is explained by a mechanism of neural reserve. Our results in older adults indicate (a) a significant correlation between leisure social activities and the response time for ON, (b) a significant correlation between link the neural activity of the left superior and medial frontal (SmFG) for ON and leisure social activities. Interestingly, the activity of the left SmFG partially mediates the relationship between social activities and OD performance. We suggest that social leisure activities may contribute to maintain ON performances in healthy aging, through a neural reserve mechanism, in relation with left SmFG activity. This region is typically involved in the access to semantic representations, guided by the emotional state. These results open interesting perspectives on the role of social leisure activities on lexical production during aging.

Background Patients with posttraumatic stress disorder (PTSD) are hyperresponsive to unexpected or potentially threatening environmental stimuli. Research in lower animals and humans suggests that sensitization of the locus coeruleus–norepinephrine system may underlie behavioral and autonomic hyperresponsiveness in PTSD. However, direct evidence linking locus coeruleus system hyperactivity to PTSD hyperresponsiveness is sparse. Methods Psychophysiological recording and functional magnetic resonance imaging were used during passive listening to brief, 95-dB sound pressure level, white noise bursts presented intermittently to determine whether behavioral and autonomic hyperresponsiveness to sudden sounds in PTSD is associated with locus coeruleus hyperresponsiveness. Results Participants with PTSD (n = 28) showed more eye-blink reflexes and larger heart rate, skin conductance, and pupil area responses to loud sounds (multivariate p = .007) compared with trauma-exposed participants without PTSD (n = 26). PTSD participants exhibited larger responses in locus coeruleus (t = 2.60, region of interest familywise error corrected), intraparietal sulcus, caudal dorsal premotor cortex, and cerebellar lobule VI (t ≥ 4.18, whole-brain familywise error corrected). Caudal dorsal premotor cortex activity was associated with both psychophysiological response magnitude and levels of exaggerated startle responses in daily life in PTSD participants (t ≥ 4.39, whole-brain familywise error corrected). Conclusions Behavioral and autonomic hyperresponsiveness in PTSD may arise from a hyperactive alerting/orienting system in which processes related to attention and motor preparation localized to lateral premotor cortex, intraparietal sulcus, and posterior superior cerebellar cortex are modulated by atypically high phasic noradrenergic influences originating in the locus coeruleus.

Automatic segmentation of chronic stroke lesion from magnetic resonance images (MRI) is motivated by the increasing need for reproducible and repeatable endpoints in clinical trials. The task is non-trivial, due to a number of confounding factors, including heterogeneous lesion intensity, irregular shape, and large deformations that render the conventional use of prior probabilistic atlases challenging. In this paper, we introduce a hidden Markov random field model that avails of a novel prior probabilistic vascular territory atlas to describe the natural vascular constraints in the brain. The vascular territory atlas is deformed in a joint registration-segmentation framework to overcome subject-specific morphological variability. T1-w and Flair sequences are used to populate our model, and a variational approach is implemented to find a solution. The performance of our model is demonstrated on two datasets, and compared to manual delineations by expert raters.

International audience; The rehabilitation of speech disorders benefits from providing visual information which may improve speech motor plans in patients. We tested the proof of concept of a rehabilitation method (Sensori-Motor Fusion, SMF; Ultraspeech player) in one post-stroke patient presenting chronic non-fluent aphasia. SMF allows visualisation by the patient of target tongue and lips movements using high-speed ultrasound and video imaging. This can improve the patient?s awareness of his/her own lingual and labial movements, which can, in turn, improve the representation of articulatory movements and increase the ability to coordinate and combine articulatory gestures. The auditory and oro-sensory feedback received by the patient as a result of his/her own pronunciation can be integrated with the target articulatory movements they watch. Thus, this method is founded on sensorimotor integration during speech. The SMF effect on this patient was assessed through qualitative comparison of language scores and quantitative analysis of acoustic parameters measured in a speech production task, before and after rehabilitation. We also investigated cerebral patterns of language reorganisation for rhyme detection and syllable repetition, to evaluate the influence of SMF on phonological-phonetic processes. Our results showed that SMF had a beneficial effect on this patient who qualitatively improved in naming, reading, word repetition and rhyme judgment tasks. Quantitative measurements of acoustic parameters indicate that the patient?s production of vowels and syllables also improved. Compared with pre-SMF, the fMRI data in the post-SMF session revealed the activation of cerebral regions related to articulatory, auditory and somatosensory processes, which were expected to be recruited by SMF. We discuss neurocognitive and linguistic mechanisms which may explain speech improvement after SMF, as well as the advantages of using this speech rehabilitation method.

L’ischemia cerebrale (IC) rappresenta l’80% degli accidenti vascolari cerebrali (AVC), seconda causa di mortalita nel mondo. Essa fa seguito all’interruzione del flusso ematico in un’arteria cerebrale. Si definisce come una riduzione della pressione di perfusione cerebrale sotto la soglia di autoregolazione fisiologica del flusso ematico cerebrale, che conduce a un insufficiente apporto in ossigeno e in energia. Si tratta di un fenomeno che evolve molto rapidamente nel tempo e nello spazio, andando dal «silenzio elettrofisiologico» di neuroni ancora vitali (penombra) alla necrosi irreversibile (infarto). La risonanza magnetica o la TC di perfusione permettono di visualizzare in urgenza queste zone di IC. I meccanismi che inducono la morte cellulare (omeostasi di Ca2+, Na+/Cl–, K+ ed eccitotossicita, depolarizzazione peri-infartuale, stress ossidativo, infiammazione, ecc.) non sono limitati ai neuroni. Essi coinvolgono l’insieme dell’unita neurovascolare, gli oligodendrociti e la microglia. Inoltre, l’immunodepressione sistemica causata dall’AVC e responsabile di infezioni che peggiorano la prognosi funzionale. E necessaria una migliore comprensione integrativa «al di la del neurone» di questi fenomeni per sviluppare dei trattamenti limitati, a tutt’oggi, alla gestione specializzata delle AVC, alla riperfusione per trombolisi e all’emicraniectomia decompressiva per gli infarti estesi. Parallelamente ai meccanismi deleteri, esistono una neuroprotezione endogena iniziale e, poi, un recupero che dura diversi mesi. Questo recupero, facilitato dalla rieducazione, e legato a un compenso dei deficit e alla plasticita cerebrale: riorganizzazione dei circuiti danneggiati e neurosinaptogenesi in relazione con la glia e i microvasi all’interno di «nicchie neuro-oligo-vascolari» perilesionali. L’ottimizzazione di questa plasticita multicellulare e, oggi, l’obiettivo di trattamenti promettenti di medicina rigenerativa basati sull’utilizzo di fattori di crescita e di cellule staminali o differenziate (terapia cellulare).

Although older adults exhibit normal accuracy in performing word retrieval and generation (lexical production; e.g., object naming), they are generally slower in responding than younger adults. To maintain accuracy, older adults recruit compensatory mechanisms and strategies. We focused on two such possible compensatory mechanisms, one semantic and one executive. These mechanisms are reflected at inter- and intra-hemispheric levels by various patterns of reorganization of lexical production cerebral networks. Hemispheric reorganization (HR) changes were also evaluated in relation to increase naming latencies. Using functional magnetic resonance imaging (fMRI), we examined 27 healthy participants (from 30 years to 85 years) during an object naming task, exploring and identifying task-related patterns of cerebral reorganization. We report two main results. First, we observed a left intra-hemispheric pattern of reorganization, the left anterior-posterior aging (LAPA) effect, consisting of supplementary activation of left posterior (temporo-parietal) regions in older adults and asymmetric activation along the left fronto-temporal axis. This pattern suggests that older adults recruit posterior semantic regions to perform object naming. The second finding consisted of bilateral recruitment of frontal regions to maintain appropriate response times, especially in older adults who were faster performers. This pattern is discussed in terms of compensatory mechanism. We suggest that aging is associated with multiple, co-existing compensation and reorganization mechanisms and patterns associated with lexical production.

BACKGROUND: Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous. PURPOSE: Our aim was to evaluate the consistency across studies of HIV effects on DTI measures and then examine the DTI reliability in a longitudinal seropositive cohort. DATA SOURCES: Published studies and investigators. STUDY SELECTION: The meta-analysis included 16 cross-sectional studies reporting fractional anisotropy and 12 studies reporting mean diffusivity in the corpus callosum. DATA ANALYSIS: Random-effects meta-analysis was used to estimate study standardized mean differences and heterogeneity. DTI longitudinal reliability was estimated in seropositive participants studied before and 3 and 6 months after beginning treatment. DATA SYNTHESIS: Meta-analysis revealed lower fractional anisotropy (standardized mean difference, −0.43; P 0.96. LIMITATIONS: Many studies pooled participants with varying treatments, ages, and disease durations. CONCLUSIONS: HIV effects on WM microstructure had substantial variations that could result from acquisition, processing, or cohort-selection differences. When acquisition parameters and processing were carefully controlled, the resulting DTI measures did not show high temporal variation. HIV effects on WM microstructure may be age-dependent. The high longitudinal reliability of DTI WM microstructure measures makes them promising disease-activity markers.

Diffusion Tensor Imaging (DTI), the Fractional Anisotropy (FA) is used to measure the integrity of the white matter (WM); it is considered as a biomarker for stroke recovery. This measure is highly sensitive to applied pre-processing steps; in particular, the presence of a lesion may result into severe misregistration. In this paper, it is proposed to quantitatively assess the impact of large stroke lesions onto the registration process. To reduce this impact, a new registration algorithm, that localizes the lesion via Bayesian estimation, is proposed.

International audience; Stroke, resulting in focal structural damage, induces changes in brain function at both local and global levels. Following stroke, cerebral networks present structural, and functional reorganization to compensate for the dysfunctioning provoked by the lesion itself and its remote effects. As some recent studies underlined the role of the contralesional hemisphere during recovery, we studied its role in the reorganization of brain function of stroke patients using resting state fMRI and graph theory. We explored this reorganization using the "hub disruption index" (κ), a global index sensitive to the reorganization of nodes within the graph. For a given graph metric, κ of a subject corresponds to the slope of the linear regression model between the mean local network measures of a reference group, and the difference between that reference and the subject under study. In order to translate the use of κ in clinical context, a prerequisite to achieve meaningful results is to investigate the reliability of this index. In a preliminary part, we studied the reliability of κ by computing the intraclass correlation coefficient in a cohort of 100 subjects from the Human Connectome Project. Then, we measured intra-hemispheric κ index in the contralesional hemisphere of 20 subacute stroke patients compared to 20 age-matched healthy controls. Finally, due to the small number of patients, we tested the robustness of our results repeating the experiment 1000 times by bootstrapping on the Human Connectome Project database. Statistical analysis showed a significant reduction of κ for the contralesional hemisphere of right stroke patients compared to healthy controls. Similar results were observed for the right contralesional hemisphere of left stroke patients. We showed that κ, is more reliable than global graph metrics and more sensitive to detect differences between groups of patients as compared to healthy controls. Using new graph metrics as κ allows us to show that stroke induces a network-wide pattern of reorganization in the contralesional hemisphere whatever the side of the lesion. Graph modeling combined with measure of reorganization at the level of large-scale networks can become a useful tool in clinic.

Introduction/Background The sense of verticality results from a complex multisensory integration suggesting the existence of internal models of verticality perception. Recent data from our team suggest that the parietal operculum, the posterior insula and the posterior-lateral thalamus, in the right hemisphere, constitute the core polymodal regions that construct and update the internal models of verticality. The aim of this study was double. First, to analyse functional connectivity, in a group of healthy participants, of the three core regions in a larger verticality perception network, established on literature data. Second, to analyse functional connectivity of these three regions in a group of stroke patients presenting an altered perception of verticality. Material and method Functional connectivity was studied using ROI-to-ROI method in Connectivity toolbox with resting state functional Magnetic Resonance Imaging (fMRI). The regions of interest were selected from Anatomy toolbox, with source regions OP1, OP2, Ig1, Ig2, parietal and somatosensory thalamus. The first study concerned 74 healthy participants and the second study concerned 5 stroke patients with altered verticality perception in visual modality. Results In the healthy participants group, the three regions (represented by OP1, OP2, Ig1, Ig2, ThP and ThS) constitute a highly connected network in both hemispheres. In stroke patients group, this network was globally preserved in the healthy hemisphere, but disrupted in the brain-damaged hemisphere. Moreover, we observed a correlation between the loss of inter-hemispheric connectivity within this network and the altered perception of verticality in the visual modality. Conclusion The parietal operculum, the posterior insula and the posterior-lateral thalamus form a network that could correspond to the ‘sense of upright’ network.

In the last decade, functional MRI (fMRI) has become one of the most widely used functional imaging technique in neurosciences. However, its clinical applications remain limited. Despite methodological and practical issues, fMRI data has been validated by different techniques (magnetoencephalography, Wada test, electrical and magnetic stimulations, and surgical resections). In neurosurgical practice, fMRI can identify eloquent areas involved in motor and language functions, and may evaluate characteristics of postoperative neurological deficit including its occurrence, clinical presentation and duration. This may help to inform patients and to prepare postoperative care. fMRI may also identify epileptic foci. In neurological practice, fMRI may help to determine prognosis of recovery after stroke, appropriate medication, and rehabilitation. fMRI may help to identify patients at risk of developing Alzheimer disease. Finally, cerebrovascular reactivity imaging is an interesting approach that might provide new radiological insights of vascular function.

Background: Little is known about the relationship between hypercholesterolaemia and specific aetiological subtypes of brain infarction (BI). Methods: In a cross-sectional study of 492 pairs of patients with a BI proven by MRI and matched hospital controls, we determined the blood levels of triglycerides, total, HDL and LDL cholesterol, and apolipoprotein A1 and B, in the same centralized laboratory. We performed aetiological BI subtype classification. Results: Except for triglycerides, the risk of BI increased continuously with the lipid levels, without any heterogeneity between the main BI subtypes or the group on lipid-lowering therapy. The adjusted odds ratio per standard deviation in LDL cholesterol (0.93 mmol/l) was 1.74 (95% confidence interval, 1.02–2.98) in atherothrombotic strokes (n = 109) and 2.71 (95% confidence interval, 1.60–4.55) in lacunar strokes (n = 105). Eighty percent of patients were above the ATP-III guideline threshold LDL cholesterol of 2.59 mmol/l (100 mg/dl), with a major contribution of both atherothrombotic and lacunar stroke subtypes to this group. Conclusions: These findings suggest that blood lipids, particularly total and LDL cholesterol levels, are associated with all subtypes of BI, and that LDL above 2.59 mmol/l is highly prevalent.

While experimental studies in the monkey have shown that motor recovery after partial destruction of the hand motor cortex was based on adjacent motor reorganization, functional MRI (fMRI) studies with isolated primary motor cortical stroke have not yet been reported in humans. Based on experimental data, we designed a study to test if recovery after stroke within primary motor cortex (M1) was associated with reorganization within the surrounding motor cortex, i.e. the motor cortex was able to vicariate. Since motor recovery is time-dependent and might be inflected according to the tested task, the delay after stroke and two motor tasks were included in our design. We examined four patients with one ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in a temporally balanced prospective longitudinal fMRI study over three sessions

Pain, in its various manifestations, is our most distressing human experience. A large volume of evidence extending from psychology to neuroimaging emphasizes the powerful influence of both social and physical pain on mammalian well-being and survival.1 Although pain is defined as an unpleasant sensation caused by nociceptive stimuli,2 the concept encompasses social as well as physical pain. Painful emotional feelings are associated with the loss of social connection owing to rejection, exclusion from a group, personal failure, or the death of a loved one. We often describe the experience of social pain by using terms for physical pain,1 making reference . . .

Resume L’hypoglycemie est une cause de coma frequente et grave. Les indicateurs du pronostic, telles la severite de l’hypoglycemie et la duree du coma, sont peu nombreux et leur fiabilite est incertaine. Nous rapportons un cas de coma hypoglycemique associe a la presence d’hypersignaux en IRM de diffusion, suivie de l’installation rapide d’une atrophie cerebrale au niveau des memes aires. Ces constatations suggerent que l’IRM de diffusion serait un marqueur des lesions neuronales dans l’hypoglycemie et pourrait constituer un indicateur du pronostic.

International audience; ObjectiveTo assess the efficiency of Visual Feedback (VF) on language recovery and plasticity in three chronic non-fluent aphasic patients. VF is based on language-action interaction, thus, language skills are improved by rehabilitation strategies based on execution and observation of motor actions. VF is an ultrasound system coupled with video images, allowing patients to ‘see their own lips and tongue at work’ during speech and improve their awareness of their lingual and labial movements and their ability to coordinate and combine phonemes and syllables. Brain plasticity was explored with functional MRI.Material/Patients and methods– Control group tested with functional MRI to identify language networks underlying three tasks of interest;– three patients with non-fluent chronic aphasia after ischemic stroke, were examined in neuropsychology, speech therapy, acoustics and fMRI, before and after VF. VF has been applied during 14 sessions (2 weeks, 1 per day). The performance was evaluated before and after VF. In fMRI, specific comparisons were performed to identify: – patterns of reorganization reflecting spontaneous neuro-plasticity, – the effect of VF on speech recovery and language plasticity.ResultsAfter 14 sessions of VF, acoustic analyses showed a more canonical vowel production and better repetition of consonants. Speech analysis for repetition of syllables, naming and rhytme judgment, showed a general improvement of performances, variable among patients. In terms of cerebral activation, various patterns of language reorganization were obtained according to task and level of language recovery. A general trend can be identified with the improvement of language performance after VF, which is a right hemispheric predominance before VF, followed by a return of the activity to the left hemisphere, after VF.Discussion - ConclusionResults are discussed according to current models of inter and intra-hemispheric reorganization of language.

Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a "glio-neurovascular niche". Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while "peripheral" stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell characterization, delivery route and in vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells and NSC are most investigated notably in clinical trials. Finally, we discuss perspectives concerning potential novel biotherapies such as combinatorial approaches (growth factor combined with cell therapy, in vitro optimization of cell products, or co-transplantation) and the development of biomaterials, which could be used as injectable hydrogel scaffold matrices that could protect a cell graft or selectively deliver drugs and growth factors into the post-stroke cavity at chronic stages. Considering the remaining questions about the best procedure and the safety cautions, we can hope that future translational research about biotherapies will bring more efficient treatments that will decrease post-stroke disability for many patients.