American Association for Cancer Research Genetics and Biology of Brain Cancers 2009, December 13–15, 2009, San Diego, CA

Molecularly targeted therapies promise to transform the treatment of cancer patients, including those with brain tumors. A deeper understanding of the biology of brain tumors has led to a palpable excitement that new and more effective treatments are on the horizon for these deadly diseases. This conference brought basic, genomic, and translational scientists together with clinicians to discuss how to develop more effective molecularly targeted therapies for brain tumor patients based on a mechanistic understanding of the molecular circuitry and biology of the disease

Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk.

BackgroundThe development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment.Main bodyRecent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD.ConclusionThe understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods

Non-invasive brain stimulation and plasticity changes in aging

Our conceptualization of brain changes across the lifespan is evolving (Pascual-Leone et al., 2011). There appears to be no period when the brain and its functions are static. Instead, changes are continuous throughout the lifespan, some resulting in benefits, others in functional loss and decline (Park and Reuter-Lorenz, 2009; Pascual-Leone and Taylor, 2011). Therefore, the most suitable framework appears to be that of life-long, continued “developmental” processes that influence each other, and there is a growing need for deeper understanding of brain changes (plasticity) from prenatal states and infancy through childhood into adult and old age..

Redundant variables and Granger causality

We discuss the use of multivariate Granger causality in presence of redundant variables: the application of the standard analysis, in this case, leads to under-estimation of causalities. Using the un-normalized version of the causality index, we quantitatively develop the notions of redundancy and synergy in the frame of causality and propose two approaches to group redundant variables: (i) for a given target, the remaining variables are grouped so as to maximize the total causality and (ii) the whole set of variables is partitioned to maximize the sum of the causalities between subsets. We show the application to a real neurological experiment, aiming to a deeper understanding of the physiological basis of abnormal neuronal oscillations in the migraine brain. The outcome by our approach reveals the change in the informational pattern due to repetitive transcranial magnetic stimulations.Comment: 4 pages, 5 figures. Accepted for publication in Physical Review

Magnetic resonance spectroscopy — Revisiting the biochemical and molecular milieu of brain tumors

AbstractBackgroundMagnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of ‘live biochemistry’ helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above.Scope of reviewPresented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice.Major conclusionsMR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same.General significanceThe review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology

ADVANCED OPTICAL TECHNIQUES TO EXPLORE BRAIN STRUCTURE AND FUNCTION

Understanding brain structure and function, and the complex relationships between them, is one of the grand challenges of contemporary sciences. Thanks to their flexibility, optical techniques could be the key to explore this complex network. In this manuscript, we briefly review recent advancements in optical methods applied to three main issues: anatomy, plasticity and functionality. We describe novel implementations of light-sheet microscopy to resolve neuronal anatomy in whole fixed brains with cellular resolution. Moving to living samples, we show how real-time dynamics of brain rewiring can be visualized through two-photon microscopy with the spatial resolution of single synaptic contacts. The plasticity of the injured brain can also be dissected through cutting-edge optical methods that specifically ablate single neuronal processes. Finally, we report how nonlinear microscopy in combination with novel voltage sensitive dyes allow optical registrations of action potential across a population of neurons opening promising prospective in understanding brain functionality. The knowledge acquired from these complementary optical methods may provide a deeper comprehension of the brain and of its unique features

The Boy Who Grew a New Brain: Understanding this Miracle from a Neuro-Quantum Perspective

In this paper, we present a case of a boy – Noah Wall, who till today surprises the world of neuroscience with his will to grow his brain and survive. The case presented in this study sets a stepping stone in understanding the advent of the will to make a choice, from a neuro-quantum mechanics interpretation. We propose that besides our internal states of choices (neurogenesis, neuroplasticity, cell differentiation, etc.) we also relate with external states of choices (love, compassion, empathy, emotions, etc.) that contributes to its emergence. Quantum uncertainty seems to support the existence of a fundamental property based on which the universe functions; which means that even the nothing of free space has a small chance of containing something. Outcomes are not determined by prior or random events but by consciousness that gives rise to these outcomes. This provides us a lead into understanding the existence of the will and the origin of choice when we look deeper into the realms of the implausible interpretations of quantum mechanics. Free will is the ability for the mind to choose between possible outcomes. Willful power is therefore not only a psychological intervention but also a biological and quantum intervention, where we have the capacity to make choices about what direction we will take, making a change to the systematic functioning of our body

Development of Novel Models to Study Deep Brain Effects of Cortical Transcranial Magnetic Stimulation

Neurological disorders require varying types and degrees of treatments depending on the symptoms and underlying causes of the disease. Patients suffering from medication-refractory symptoms often undergo further treatment in the form of brain stimulation, e.g. electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or transcranial magnetic stimulation (TMS). These treatments are popular and have been shown to relieve various symptoms for patients with neurological conditions. However, the underlying effects of the stimulation, and subsequently the causes of symptom-relief, are not very well understood. In particular, TMS is a non-invasive brain stimulation therapy which uses time-varying magnetic fields to induce electric fields on the conductive parts of the brain. TMS has been FDA-approved for treatment of major depressive disorder for patients refractory to medication, as well as symptoms of migraine. Studies have shown that TMS has relieved severe depressive symptoms, although researchers believe that it is the deeper regions of the brain which are responsible for symptom relief. Many experts theorize that cortical stimulation such as TMS causes brain signals to propagate from the cortex to these deep brain regions, after which the synapses of the excited neurons are changed in such a way as to cause plasticity. It has also been widely observed that stimulation of the cortex causes signal firing at the deeper regions of the brain. However, the particular mechanisms behind TMS-caused signal propagation are unknown and understudied. Due to the non-invasive nature of TMS, this is an area in which investigation can be of significant benefit to the clinical community. We posit that a deeper understanding of this phenomenon may allow clinicians to explore the use of TMS for treatment of various other neurological symptoms and conditions. This thesis project seeks to investigate the various effects of TMS in the human brain, with respect to brain tissue stimulation as well as the cellular effects at the level of neurons. We present novel models of motor neuron circuitry and fiber tracts that will aid in the development of deep brain stimulation modalities using non-invasive treatment paradigms