Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition.

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control. Modafinil effects were evaluated both within this patient group and compared to a healthy subject group. Modafinil modulated activity in the locus coeruleus (LC) and ventral tegmental area (VTA) in the patient group. However, compared to the healthy comparison group, these effects were altered as a function of task demands: the control-independent drug effect on deactivation was relatively attenuated (shallower) in the LC and exaggerated (deeper) in the VTA; in contrast, again compared to the comparison group, the control-related drug effects on positive activation were attenuated in LC, VTA and the cortical cognitive control network. These altered effects in the LC and VTA were significantly and specifically associated with the degree of antagonism of alpha-2 adrenergic and dopamine-2 receptors, respectively, by concurrently prescribed antipsychotics. These sources of evidence suggest interacting effects on catecholamine neurons of chronic antipsychotic treatment, which respectively increase and decrease sustained neuronal activity in LC and VTA. This is the first direct evidence in a clinical population to suggest that antipsychotic medications alter catecholamine neuronal activity to mitigate pro-cognitive drug action on cortical circuits

Reading out a spatiotemporal population code by imaging neighbouring parallel fibre axons in vivo.

The spatiotemporal pattern of synaptic inputs to the dendritic tree is crucial for synaptic integration and plasticity. However, it is not known if input patterns driven by sensory stimuli are structured or random. Here we investigate the spatial patterning of synaptic inputs by directly monitoring presynaptic activity in the intact mouse brain on the micron scale. Using in vivo calcium imaging of multiple neighbouring cerebellar parallel fibre axons, we find evidence for clustered patterns of axonal activity during sensory processing. The clustered parallel fibre input we observe is ideally suited for driving dendritic spikes, postsynaptic calcium signalling, and synaptic plasticity in downstream Purkinje cells, and is thus likely to be a major feature of cerebellar function during sensory processing

Longitudinal Optogenetic Motor Mapping Revealed Structural and Functional Impairments and Enhanced Corticorubral Projection after Contusive Spinal Cord Injury in Mice

Current evaluation of impairment and repair after spinal cord injury (SCI) is largely dependent on behavioral assessment and histological analysis of injured tissue and pathways. Here, we evaluated whether transcranial optogenetic mapping of motor cortex could reflect longitudinal structural and functional damage and recovery after SCI. In Thy1-Channelrhodopsin2 transgenic mice, repeated motor mappings were made by recording optogenetically evoked electromyograms (EMGs) of a hindlimb at baseline and 1 day and 2, 4, and 6 weeks after mild, moderate, and severe spinal cord contusion. Injuries caused initial decreases in EMG amplitude, losses of motor map, and subsequent partial recoveries, all of which corresponded to injury severity. Reductions in map size were positively correlated with motor performance, as measured by Basso Mouse Scale, rota-rod, and grid walk tests, at different time points, as well as with lesion area at spinal cord epicenter at 6 weeks post-SCI. Retrograde tracing with Fluoro-Gold showed decreased numbers of cortico- and rubrospinal neurons, with the latter being negatively correlated with motor map size. Combined retro- and anterograde tracing and immunostaining revealed more neurons activated in red nucleus by cortical stimulation and enhanced corticorubral axons and synapses in red nucleus after SCI. Electrophysiological recordings showed lower threshold and higher amplitude of corticorubral synaptic response after SCI. We conclude that transcranial optogenetic motor mapping is sensitive and efficient for longitudinal evaluation of impairment and plasticity of SCI, and that spinal cord contusion induces stronger anatomical and functional corticorubral connection that may contribute to spontaneous recovery of motor function

Learning the meaning of new stimuli increases the cross-correlated activity of prefrontal neurons

The prefrontal cortex (PF) has a key role in learning rules and generating associations between stimuli and responses also called conditional motor learning. Previous studies in PF have examined conditional motor learning at the single cell level but not the correlation of discharges between neurons at the ensemble level. In the present study, we recorded from two rhesus monkeys in the dorsolateral and the mediolateral parts of the prefrontal cortex to address the role of correlated firing of simultaneously recorded pairs during conditional motor learning. We trained two rhesus monkeys to associate three stimuli with three response targets, such that each stimulus was mapped to only one response. We recorded the neuronal activity of the same neuron pairs during learning of new associations and with already learned associations. In these tasks after a period of fixation, a visual instruction stimulus appeared centrally and three potential response targets appeared in three positions: right, left, and up from center. We found a higher number of neuron pairs significantly correlated and higher cross-correlation coefficients during stimulus presentation in the new than in the familiar mapping task. These results demonstrate that learning affects the PF neural correlation structure

Machine Learning in Wireless Sensor Networks: Algorithms, Strategies, and Applications

Wireless sensor networks monitor dynamic environments that change rapidly over time. This dynamic behavior is either caused by external factors or initiated by the system designers themselves. To adapt to such conditions, sensor networks often adopt machine learning techniques to eliminate the need for unnecessary redesign. Machine learning also inspires many practical solutions that maximize resource utilization and prolong the lifespan of the network. In this paper, we present an extensive literature review over the period 2002-2013 of machine learning methods that were used to address common issues in wireless sensor networks (WSNs). The advantages and disadvantages of each proposed algorithm are evaluated against the corresponding problem. We also provide a comparative guide to aid WSN designers in developing suitable machine learning solutions for their specific application challenges.Comment: Accepted for publication in IEEE Communications Surveys and Tutorial

Spatiotemporally dissociable neural signatures for generating and updating expectation over time in children: A High Density-ERP study

Temporal orienting (TO) is the allocation of attentional resources in time based on the a priori generation of temporal expectancy of relevant stimuli as well as the a posteriori updating of this expectancy as a function of both sensory-based evidence and elapsing time. These processes rely on dissociable cognitive mechanisms and neural networks. Yet, although there is evidence that TO may be a core mechanism for cognitive functioning in childhood, the developmental spatiotemporal neural dynamics of this mechanism are little understood. In this study we employed a combined approach based on the application of distributed source reconstruction on a high spatial resolution ERP data array obtained from eighteen 8- to 12-year-old children completing a TO paradigm in which both the cue (Temporal vs. Neutral) and the SOA (Short vs. Long) were manipulated. Results show both cue (N1) and SOA (CNV, Omission Detection Potential and Anterior Anticipatory Index) ERP effects, which were associated with expectancy generation and updating, respectively. Only cue-related effects were correlated with age, as revealed by a reduction of the N1 delta effect with increasing age. Our data suggest that the neural correlates underlying TO are already established at least from 8 to 12 years of age

Source and dynamics of a volcanic caldera unrest : Campi Flegrei, 1983–84

Acknowledgements We thank Tiziana Vanorio, Antonella Amoruso, Luca Crescentini, Nicholas Rawlinson, Yasuko Takei, and David Cornwell for the valuable suggestions regarding the methodology and interpretation. Reviews from Tim Greenfield and two anonymous reviewers helped improving both clarity of the manuscript and interpretation. The Royal Society of Edinburgh - Accademia dei Lincei Bilateral Agreement, the Santander Mobility Award of the College of Physical Sciences, University of Aberdeen, and the TIDES EU COST action granted L.D.S. travel grants for the realisation of this study. E.D.P. has been supported by the EPHESTO and KNOWAVES projects, funded by the Spanish Ministry of Education and Science.Peer reviewedPublisher PD