Ipsilateral hand impairment predicts long-term outcome in patients with subacute stroke.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

White matter tract disruption is associated with ipsilateral hand impairment in subacute stroke: a diffusion MRI study.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Speech recovery and language plasticity can be facilitated by Sensori-Motor Fusion training in chronic non-fluent aphasia. A case report study.

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.

Upper limb recovery after stroke is associated with ipsilesional primary motor cortical activity: a meta-analysis.

BACKGROUND AND PURPOSE: Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. METHODS: Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke. RESULTS: When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems. CONCLUSIONS: Activity in ipsilesional primary motor and medial-premotor cortices in chronic stroke signals good motor recovery, whereas cerebellar vermis activity signals poor recovery. Functional MRI may be useful in identifying recovery biomarkers.

Surface-Based Cortical Measures in Multimodal Association Brain Regions Predict Chess Expertise.

The complex structure of the brain supports high-order cognition, which is crucial for mastering chess. Surface-based measures, including the fractional dimension (FD) and gyrification index (GI), may be more sensitive in detecting cortical changes relative to volumetric indexes. For this reason, structural magnetic resonance imaging data from 29 chess experts and 29 novice participants were analyzed using the CAT12 toolbox. FD and GI for each brain region were compared between the groups. A multivariate model was used to identify surface-based brain measures that can predict chess expertise. In chess experts, FD is increased in the left frontal operculum (p < 0.01), and this change correlates with the starting age of chess practice (ρ = −0.54, p < 0.01). FD is decreased in the right superior parietal lobule (p < 0.01). Chess expertise is predicted by the FD in a network of fronto-parieto-temporal regions and is associated with GI changes in the middle cingulate gyrus (p < 0.01) and the superior temporal sulcus (p < 0.01). Our findings add to the evidence that chess expertise is based on the complex properties of the brain surface of a network of transmodal association areas important for flexible high-level cognitive functions. Interestingly, these changes are associated with long-lasting practice, suggesting that neuroplastic effects develop over time.

Predicting cognitive dysfunctioning in nondemented patients early after stroke.

BACKGROUND: Cognitive dysfunctioning (CDF) is an important issue in stroke, interfering with recovery and social dysfunctioning. We aimed to investigate the clinical and imaging correlates of CDF in patients with a first-ever subacute ischemic stroke and no dementia. METHODS: We evaluated CDF 15 days after stroke in a prospective cohort of consecutive patients with a Mini Mental State Examination score > or =23 using a comprehensive neuropsychological battery. CDF was ranked into 3 categories according to Z scores calculated for each test and adjusted for age and education. CDF was analyzed in relation to stroke features. Imaging was assessed using MRI. An ordinal regression procedure was used to determine the clinical correlates of CDF and to compute probabilities. RESULTS: Cognitive evaluation was achieved in 177 consecutive patients (age 50.0 +/- 16.0 years). In bivariate analysis, CDF was associated with age, low level of education, depression, neurological deficit at day 15, stroke subtype, arterial territory and leukoaraiosis but not with stroke volume or location. The predictors of CDF were NIHSS score at day 15 (OR = 1.35; 95% CI = 1.05-1.73), middle cerebral artery infarct (OR = 2.96; 95% CI = 1.30-6.73), depression interacting with left stroke side (OR = 1.09; 95% CI = 1.03-1.15), and female gender interacting with high level of education (OR = 0.209; 95% CI = 0.085-0.514). CONCLUSIONS: Stroke features correlate with CDF in nondemented patients. These simple criteria may help to predict CDF at bedside in the subacute phase after stroke and to recommend a neuropsychological evaluation for patients' management. Modeling CDF soon after stroke using simple neurological criteria may be a useful tool for designing clinical trials.

Using tools effectively despite defective hand posture: A single-case study.

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.

Functional Connectivity in Chronic Nonbothersome Tinnitus Following Acoustic Trauma: A Seed-Based Resting-State Functional Magnetic Resonance Imaging Study.

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.

Spatiotemporal patterns of sensorimotor fMRI activity influence hand motor recovery in subacute stroke: A longitudinal task-related fMRI study.

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.

Motor tract integrity predicts walking recovery: A diffusion MRI study in subacute stroke.

OBJECTIVE: To 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. METHODS: Walking 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. RESULTS: We 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. CONCLUSIONS: We 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.

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial.

While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity. ClinicalTrials.gov Identifier NCT00875654.

Hidden dysfunctioning in subacute stroke.

BACKGROUND AND PURPOSE: Determining cognitive dysfunctioning (CDF) after stroke is an important issue because it influences choices for management in terms of return to previous activities. Because previous research in subacute stroke has shown important variations in CDF rates, we aimed to describe the frequency and neuropsychological profile of CDF in subacute stroke outside dementia. We used a large battery of tests to screen any potentially hidden CDF. METHODS: Patients with Mini-Mental State Examination scores >or=23 were prospectively and consecutively included 2 weeks after a first-ever ischemic brain infarct. Stroke features were based on MRI. Four domains were evaluated: instrumental and executive functions, episodic memory, and working memory (WM). Patients were scored using means and compared with education- and age-matched control subjects. Then we attributed Z-scores for each test and each domain. The most relevant cognitive tests characterizing CDF were determined using logistic regression. RESULTS: Among 177 patients (mean age, 50.6 years), 91.5% failed in at least one cognitive domain. WM was the most impaired domain (87.6%) with executive functions (64.4%), episodic memory (64.4%), and instrumental functions (24.9%) being relatively preserved. CDF was associated with age, education, depression, neurological deficit, and leukoaraiosis in bivariate analysis. Using logistic regression, WM tests and age predicted CDF (Modified Paced Auditorial Serial Addition Test: OR=0.96 CI=0.93 to 0.98; Owen-spatial-WM: OR=1.07 CI=1.02 to 1.12; age: OR=0.96 CI=0.93 to 0.98). CONCLUSIONS: CDF appears to be almost constant, although underestimated, in subacute stroke. WM could reflect some hidden dysfunctioning, which may interfere with rehabilitation and return to work. Clinical routine may include WM tests in young patients with mild stroke.

Gray Matter Volume and Cognitive Performance During Normal Aging. A Voxel-Based Morphometry Study.

Normal aging is characterized by decline in cognitive functioning in conjunction with extensive gray matter (GM) atrophy. A first aim of this study was to determine GM volume differences related to aging by comparing two groups of participants, middle-aged group (MAG, mean age 41 years, N = 16) and older adults (OG, mean age 71 years, N = 14) who underwent an magnetic resonance images (MRI) voxel-based morphometry (VBM) evaluation. The VBM analyses included two optimized pipelines, for the cortex and for the cerebellum. Participants were also evaluated on a wide range of cognitive tests assessing both domain-general and language-specific processes, in order to examine how GM volume differences between OG and MAG relate to cognitive performance. Our results show smaller bilateral GM volume in the OG relative to the MAG, in several cerebral and right cerebellar regions involved in language and executive functions. Importantly, our results also revealed smaller GM volume in the right cerebellum in OG relative to MAG, supporting the idea of a complex cognitive role for this structure. This study provides a broad picture of cerebral, but also cerebellar and cognitive changes associated with normal aging.

Effect of social leisure activities on object naming in healthy aging A multimodal approach.

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.

Locus Coeruleus Activity Mediates Hyperresponsiveness in Posttraumatic Stress Disorder.

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.

Controlled clinical trials of cell therapy in stroke: Meta-analysis at six months after treatment.

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.

Aging Modulates the Hemispheric Specialization during Word Production.

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.