Predicting Clinical Outcome of Stroke Patients with Tractographic Feature

The volume of stroke lesion is the gold standard for predicting the clinical outcome of stroke patients. However, the presence of stroke lesion may cause neural disruptions to other brain regions, and these potentially damaged regions may affect the clinical outcome of stroke patients. In this paper, we introduce the tractographic feature to capture these potentially damaged regions and predict the modified Rankin Scale (mRS), which is a widely used outcome measure in stroke clinical trials. The tractographic feature is built from the stroke lesion and average connectome information from a group of normal subjects. The tractographic feature takes into account different functional regions that may be affected by the stroke, thus complementing the commonly used stroke volume features. The proposed tractographic feature is tested on a public stroke benchmark Ischemic Stroke Lesion Segmentation 2017 and achieves higher accuracy than the stroke volume and the state-of-the-art feature on predicting the mRS grades of stroke patients. In addition, the tractographic feature also yields a lower average absolute error than the commonly used stroke volume feature.Comment: 12 pages, 4 figures, 3 tables. Accepted by MICCAI-BrainLesion 2019 as an oral presentatio

Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy

A Novel Interhemispheric Interaction: Modulation of Neuronal Cooperativity in the Visual Areas

Background: The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres. Methods/Principal Findings: To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate. Conclusions/Significance: These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization

Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report

BACKGROUND: After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants. CASE PRESENTATION: The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age. CONCLUSION: Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation

Functional activation of microgyric visual cortex in a human.

(+)-Ryanodine is a natural product modulator of ryanodine receptors, important intracellular calcium ion channels that play a critical role in signal transduction leading to muscle movement and synaptic transmission. Chemical derivatization of (+)-ryanodine has demonstrated that certain peripheral structural modifications can alter its pharmacology, and that the pyrrole-2-carboxylate ester is critical for high affinity binding to ryanodine receptors. However, the structural variation of available ryanodine analogues has been limited by the challenge of site-specific functionalization of semisynthetic intermediates, such as (+)-ryanodol. Here we report a synthetic strategy that provides access to (+)-ryanodine and the related natural product (+)-20-deoxyspiganthine in 18 and 19 steps, respectively. A key feature of this strategy is the reductive cyclization of an epoxide intermediate that possesses the critical pyrrole-2-carboxylate ester. This approach allows for the direct introduction of this ester in the final stage of the synthesis and provides a framework for the synthesis of previously inaccessible synthetic ryanoids

Functional activation of microgyric visual cortex in a human.

We report on the case of a 20-year-old man with bilateral parasagittal parieto-occipital polymicrogyria and epilepsy. Functional magnetic resonance imaging responses to reversing checkerboard and interhemispheric electroencephalogram coherence changes to moving gratings were investigated. Results of both studies indicate that the polymicrogyric cortex was activated by visual stimuli, suggesting preserved function in the dysplastic area

The Formation of an Anti-Cancer Complex Under Simulated Gastric Conditions

This is the author’s version of a work that was accepted for publication in Food Digestion. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Food Digestion, 2013, 4(1), 7-18. The final publication is available at http://link.springer.com, DOI: 10.1007/s13228-012-0030-0.peer-reviewedA potent anti-cancer complex has previously been formed from two major components of milk. Human/bovine α-lactalbumin made lethal to tumour cells (H/BAMLET) is a protein–fatty acid complex that has been produced using the whey protein α-lactalbumin (α-LA) and the fatty acid oleic acid (OA). It was shown that it possesses selective anti-tumour and anti-microbial activity, which was first identified in acidic fractions of human breast milk. The aim of this study was to determine whether the two components would form a bioactive complex during simulated gastric (GI) transit. Results showed that a complex consisting of α-LA and OA is formed as the protein unfolds under acidic conditions and subsequently refolds upon pH increase. Analysis of this complex using Nuclear Magnetic Resonance and Fourier Transform Infra-Red (FTIR) spectroscopies estimated a stoichiometry of 4.1 and 4.4 oleic acids per mole of protein, respectively. FTIR and fluorescence spectroscopies showed that the structure was similar to that of BAMLET. Cytotoxicity testing against cancer cell line U937 cells showed that the complex had an LC50 value of 14.08 μM compared to 9.15 μM for BAMLET. These findings suggest that a BAMLET-like complex may be formed under the tested in vitro GI conditions.Department of Agriculture, Food and Marine, Ireland - Food Institutional Research Measure (project number 08RDTMFRC650); Teagasc Walsh Fellowship scheme; COST Action FA 1005, Infogest