Functional mapping of the human visual cortex with intravoxel incoherent motion MRI.

Functional imaging with intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is demonstrated. Images were acquired at 3 Tesla using a standard Stejskal-Tanner diffusion-weighted echo-planar imaging sequence with multiple b-values. Cerebro-spinal fluid signal, which is highly incoherent, was suppressed with an inversion recovery preparation pulse. IVIM microvascular perfusion parameters were calculated according to a two-compartment (vascular and non-vascular) diffusion model. The results obtained in 8 healthy human volunteers during visual stimulation are presented. The IVIM blood flow related parameter fD* increased 170% during stimulation in the visual cortex, and 70% in the underlying white matter.

Functional assessment of chest wall integrity after methylmethacrylate reconstruction.

BACKGROUND: All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS: Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS: There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS: Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.

Anatomic and functional outcome after 23-gauge sutureless transconjunctival vitrectomy, peeling and intravitreal triamcinolone for idiopathic macular epiretinal membranes

Purpose:To report the functional, anatomic outcome and safety profile of 23-gauge pars plana vitrectomy (PPV) combined with peeling and intravitreal injection of triamcinolone acetonide (TA) in eyes with idiopathic epiretinal membranes (ERM). Methods:Retrospective, nonrandomized study of consecutive patients who underwent 23-gauge transconjunctival sutureless PPV with subsequent membrane peeling and intravitreal TA injection for an idiopathic ERM. All patients were operated between February 2007 and February 2008 at the Jules Gonin University Eye Hospital. The minimum follow-up was 6-months. Results:Thirty-nine eyes of 39 patients were included. The mean follow-up was 7 months (SD: 2.2, range: 6-15 months). Twenty-two (56%) eyes were pseudophakic and 17 (44%) were phakic at the time of surgery. Mean preoperative intraocular pressure (IOP) was 14 mmHg (SD: 3.5). At the final follow-up mean IOP was 14.5 (SD: 2.7) that did not differ significantly from the IOP at baseline (P: 0.14- 2-tailed t test). Five patients (13%) needed temporary topical anti-glaucoma treatment.Mean preoperative BCVA was 0.28 decimal equivalent (logMAR 0.54, SD: 0.2, range: 1.0 - 0.2). and improved significantly (P <0.0001, 2-tailed t test) to a mean of 0.6 decimal equivalent (logMAR 0.22, SD: 0.16, range: 0.6 - 0) at the final follow-up. The visual acuity improved by a mean of 3.2 lines (SD 2.1, range 0- 8). Twenty-nine patients (74%) demonstrated a gain of 3 or more lines.Mean central macular thickness (CMT) was 456 µm (SD: 77) at the baseline that reduced significantly (P <0.0001, 2-tailed t test) at the final follow-up to 327µm (SD: 79). Average CMT reduction was 131µm (SD: 77, range: 36- 380 µm). A subgroup analysis of 15 selected cases that had CMT measurement 1 week after surgery demonstrated that 84% of the total final reduction in CMT occurred during the first week. Conclusions:23-gauge sutureless transconjunctival vitrectomy with the concomitant administration of intravitreal TA is a safe and effective technique for the treatment of idiopathic ERM and may speed up anatomical recovery.

Ultra-fast recovery from right neglect after 'awake surgery' for slow-growing tumor invading the left parietal area

It is now possible to perform resections of slow-growing tumors in awake patients. Using direct electrical stimulation, real-time functional mapping of the brain can be used to prevent the resection of essential areas near the tumor. Simple clinical observations of patients with a resection of slow-growing tumors have demonstrated substantial recovery within a few days of such 'awake surgery'. The aim of this study was to investigate the kinetics of recovery following the resection of slow-growing tumors invading the left parietal area and to focus mainly on its rapidity. Two patients were assessed by standard line bisection tests and compared with eight healthy individuals. Independently of the pure nature of the symptoms, we report that the patients rapidly and substantially recovered from pronounced right neglect. They were tested 48 hours after the surgery and the recovery was significant for both patients after less than 4 hours. Strikingly, for one patient, recovery was ultra fast and substantial in the first practice session within less than 7 minutes: it occurred without verbal feedback and was substantially retained during the following testing session. Its rapidity suggests a process of unmasking redundant networks. With the slow growth of the lesion, the contralesional hemisphere is probably progressively prepared for rapid unmasking of homologue networks. These results have major clinical implications. For patients with an invading left-side tumor, it is now clear that line bisections are required before, during, and after awake surgery to: plan the surgery, control the quality of the resection, and also optimize the rehabilitation of the patient

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.

Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of changes induced by spared nerve injury (SNI) to Na(v)1 mRNA levels and tetrodotoxin-sensitive and -resistant (TTX-S/TTX-R) Na(+) currents in injured and adjacent non-injured small DRG neurons. VGSC transcripts were down-regulated in injured neurons except for Na(v)1.3, which increased, while they were either unchanged or increased in non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs.

Identification of optimal structural connectivity using functional connectivity and neural modeling.

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions.

Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair.

INTRODUCTION: Functional muscle recovery after peripheral nerve injury is far from optimal, partly due to atrophy of the muscle arising from prolonged denervation. We hypothesized that injecting regenerative cells into denervated muscle would reduce this atrophy. METHODS: A rat sciatic nerve lesion was performed, and Schwann cells or adipose-derived stem cells, untreated or induced to a "Schwann-cell-like" phenotype (dASC), were injected into the gastrocnemius muscle. Nerves were either repaired immediately or capped to prevent muscle reinnervation. One month later, functionality was measured using a walking track test, and muscle atrophy was assessed by examining muscle weight and histology. RESULTS: Schwann cells and dASC groups showed significantly better scores on functional tests when compared with injections of growth medium alone. Muscle weight and histology were also significantly improved in these groups. CONCLUSION: Cell injections may reduce muscle atrophy and could benefit nerve injury patients.

Visual activity predicts auditory recovery from deafness after adult cochlear implantation.

Modern cochlear implantation technologies allow deaf patients to understand auditory speech; however, the implants deliver only a coarse auditory input and patients must use long-term adaptive processes to achieve coherent percepts. In adults with post-lingual deafness, the high progress of speech recovery is observed during the first year after cochlear implantation, but there is a large range of variability in the level of cochlear implant outcomes and the temporal evolution of recovery. It has been proposed that when profoundly deaf subjects receive a cochlear implant, the visual cross-modal reorganization of the brain is deleterious for auditory speech recovery. We tested this hypothesis in post-lingually deaf adults by analysing whether brain activity shortly after implantation correlated with the level of auditory recovery 6 months later. Based on brain activity induced by a speech-processing task, we found strong positive correlations in areas outside the auditory cortex. The highest positive correlations were found in the occipital cortex involved in visual processing, as well as in the posterior-temporal cortex known for audio-visual integration. The other area, which positively correlated with auditory speech recovery, was localized in the left inferior frontal area known for speech processing. Our results demonstrate that the visual modality's functional level is related to the proficiency level of auditory recovery. Based on the positive correlation of visual activity with auditory speech recovery, we suggest that visual modality may facilitate the perception of the word's auditory counterpart in communicative situations. The link demonstrated between visual activity and auditory speech perception indicates that visuoauditory synergy is crucial for cross-modal plasticity and fostering speech-comprehension recovery in adult cochlear-implanted deaf patients.

Combined functional and viability cardiac MR imaging in a single breathhold

The combination of cardiac viability and functional information enhances the identification of different heart tissues in the setting of ischemic heart disease. A method has recently been proposed for obtaining black-blood delayed-enhancement (DE) viability images using the stimulated-echo acquisition mode (STEAM) MRI pulse sequence in a single short breathhold. The method was validated against conventional inversion-recovery (IR) DE images for identifying regions of myocardial infarction (MI). The method was based on the acquisition of three consecutive images of the same anatomical slice. One image has T(1)-weighted contrast in which infarction appears bright. The two other images are used to construct an anatomical image of the heart, which is combined with the first image to produce a black-blood viability image. However, using appropriate modulation and demodulation frequencies, the latter two images bear useful information about myocardial deformation that results in a cardiac strain-encoding (SENC) functional image. In this work, a method is proposed for obtaining three consecutive SENC images in a single acquisition that can be combined to produce a composite image of the heart, which shows both functional and viability information. The proposed technique reduces scan time by one-half, compared with separate acquisitions of functional and viability images, and alleviates misregistration problems caused by separate breathholds.

Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart.

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.

Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

Identification and functional characterization of auxiliary enzymes of the β-oxidation in " Arabidopsis thaliana "

Abstract: The ß-oxidation is the universal pathway that allows living organisms to degrade fatty acids. leading to lipid homeostasis and carbon and energy recovery from the fatty acid molecules. This pathway is centred on four core enzymatic activities sufficient to degrade saturated fatty acids. Additional auxiliary enzymes of the ß-oxidation are necessary for the complete degradation of a larger array of molecules encompassing the unsaturated fatty acids. The main pathways of the ßoxidation of fatty acids have been investigated extensively and auxiliary enzymes are well-known in mammals and yeast. The comparison of the established ß-oxidation systems suggests that the activities that are required to proceed to the full degradation of unsaturated fatty acids are present regardless of the organism and rely on common active site templates. The precise identity of the plant enzymes was unknown. By homology searches in the genome of Arabidopsis thaliana, I identified genes. encoding for proteins that could be orthologous to the yeast or animal auxiliary enzymes Δ 3, Δ 2-enoyl-CoA isomerase, Δ 3,5, Δ 2,4 -dienoyl-CoA isomerase, and type 2 enoyl-CoA hydratase. I established that these genes are expressed in Arabidopsis and that their expression can be correlated to the expression of core ß-oxidation genes. Through the observation of chimeric fluorescent protein fusions, I demonstrated that the identified proteins are localized in the peroxisóme, the only organelle where the ß-oxidation occurs in plants. Enzymatic assays were performed with the partially purified enzymes to demonstrate that the identified enzymes can catalyze the same in vitro reactions as their non-plant orthologs. The activities in vivo of the plant enzymes were demonstrated by heterologous complementation of the corresponding yeast Saccharomyces cerevisiae mutants. The complementation was visualized using the artificial polyhydroxyalkanoate (PHA) production in yeast peroxisomes. The recombinant strains, expressing a Pseudomonas aeruginosa PHA synthase modified for a peroxisomal localization, produce this polymer that serves as a trap for the 3-hydroxyacyl-CoA intermediaries of the ßoxidation and that reflects qualitatively and quantitatively the array of molecules that are processed through the ß-oxidation. This complementation demonstrated the implication of the plant Δ 3, Δ 2-enoyl-CoA isomerases and Δ3,5, Δ2,4-dienoyl-CoA isomerase in the degradation of odd chain position unsaturated fatty acids. The presence of a monofunctional type 2 enoyl-CoA hydratase is a novel in eukaryotes. Downregulation of the corresponding gene expression in an Arabidopsis line, modified to produce PHA in the peroxisome, demonstrated thàt this enzyme participates in vivo to the conversion of the intermediate 3R-hydroxyacyl-CoA, generated by the metabolism of fatty acids with a cis (Z)-unsaturated bond on an even-numbered carbon, to the 2Eenoyl-CoA for further degradation through the core ß-oxidation cycle. Résumé: La ß-oxydation est une voie universelle de dégradation des acides gras qui permet aux organismes vivants d'assurer une homéostasie lipidique et de récupérer l'énergie et le carbone contenus dans les acides gras. Le coeur de cette voie est composé de quatre réactions enzymatiques suffisantes à la dégradation des acides gras saturés. La présence des enzymes auxiliaires de la ß-oxydation est nécessaire à la dégradation d'une gamme plus étendue de molécules comprenant les acides gras insaturés. Les voies principales de la ß-oxydation des acides gras ont été étudiées en détail et les enzymes auxiliaires sont déterminées chez les mammifères et la levure. La comparaison entre les systèmes de ß-oxydation connus suggère que les activités requises pour la dégradation complète des acides gras insaturés reposent sur la présence de site actifs similaires. L'identité précise des enzymes auxiliaires chez les plantes était inconnue. En cherchant par homologie dans le génome de la plante modèle Arabidopsis thaliana, j'ai identifié des gènes codant pour des protéines pouvant être orthologues aux enzymes auxiliaires Δ3 Δ2-enoyl-CoA isomérase, Δ 3,5 Δ 2,4-dienoyl-CoA isomérase et enoyl-CoA hydratase de type 2 d'origine fongique ou mammalienne. J'ai établi la corrélation de l'expression de ces gènes dans Arabidopsis avec celle de gènes des enzymes du coeur de la ß-oxydation. En observant des chimères de fusion avec des protéines fluorescentes, j'ai démontré que les protéines identifiées sont localisées dans le péroxysomes, le seul organelle où la ß-oxydation se déroule chez les plantes. Des essais enzymatiques ont été conduits avec ces enzymes partiellement purifiées pour démontrer que les enzymes identifiées sont capables de catalyser in vitro les mêmes réactions que leurs orthologues non végétaux. Les activités des enzymes végétales in vivo ont été .démontrées par complémentation hétérologue des mutants de délétion correspondants de levure Saccharomyces cerevisiae. La visualisation de la complémentation est rendue possible par la synthèse de polyhydroxyalcanoate (PHA) dans les péroxysomes de levure. Les souches recombinantes expriment la PHA synthase de Pseudomonas aeruginosa modifiée pour être localisée dans le péroxysome produisent ce polymère qui sert de piège pour les 3-hydroxyacylCoAs intermédiaires de la ß-oxydation et qui reflète qualitativement et quantitativement la gamme de molécules qui subit la ß-oxydation. Cette complémentation a permis de démontrer que les Δ3, Δ2-enoyl-CoA isomérases, et la Δ3.5, Δ2,4-dienoyl-CoA isomérase végétales sont impliquées dans la dégradation des acides gras insaturés en position impaire. L'enoyl-CoA hydratase de type 2 monofonctionelle est une enzyme nouvelle chez les eucaryotes. La sous-expression du gène correspondant dans une lignée d'Arabidopsis modifiée pour produite du PHA dans le péroxysome a permis de démontrer que cette enzyme participe in vivo à la dégradation des acides gras ayant une double liaison en conformation cis (Z) en position paire.

The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: a randomized controlled trial.

BACKGROUND: Upper limb paresis remains a relevant challenge in stroke rehabilitation. AIM: To evaluate if adding mirror therapy (MT) to conventional therapy (CT) can improve motor recovery of the upper limb in subacute stroke patients. DESIGN: Prospective, single-center, single-blind, randomised, controlled trial. SETTING: Subacute stroke patients referred to a Physical and Rehabilitation Medicine Unit between October 2009 and August 2011. POPULATION: Twenty-six subacute stroke patients (time from stroke <4 weeks) with upper limb paresis (Motricity Index â0/00¤ 77). METHODS: Patients were randomly allocated to the MT (N.=13) or to the CT group (N.=13). Both followed a comprehensive rehabilitative treatment. In addition, MT Group had 30 minutes of MT while the CT group had 30 minutes of sham therapy. Action Research Arm Test (ARAT) was the primary outcome measures. Motricity Index (MI) and the Functional Independence Measure (FIM) were the secondary outcome measures. RESULTS: After one month of treatment patients of both groups showed statistically significant improvements in all the variables measured (P<0.05). Moreover patients of the MT group had greater improvements in the ARAT, MI and FIM values compared to CT group (P<0.01, Glass's Î" Effect Size: 1.18). No relevant adverse event was recorded during the study. CONCLUSION: MT is a promising and easy method to improve motor recovery of the upper limb in subacute stroke patients. CLINICAL REHABILITATION IMPACT: While MT use has been advocated for acute patients with no or negligible motor function, it can be usefully extended to patients who show partial motor recovery. The easiness of implementation, the low cost and the acceptability makes this therapy an useful tool in stroke rehabilitation.