Obama proposes $100m to map the human brain

President Barack Obama on Tuesday asked Congress to spend $100 million next year on a new project to map the human brain in hopes of eventually finding cures for disorders like Alzheimer’s, epilepsy and traumatic injuries.

Obama said the so-called BRAIN Initiative could create jobs and eventually lead to answers to ailments including Parkinson’s and autism and help reverse the effect of a stroke. The president told scientists gathered in the White House’s East Room that the research has the potential to improve the lives of billions of people worldwide.

‘‘As humans we can identify galaxies light-years away,’’ Obama said. ‘‘We can study particles smaller than an atom, but we still haven’t unlocked the mystery of the three pounds of matter that sits between our ears.’’

BRAIN stands for Brain Research through Advancing Innovative Neurotechnologies. The idea, which Obama first proposed in his State of the Union address, would require the development of new technology that can record the electrical activity of individual cells and complex neural circuits in the brain ‘‘at the speed of thought,’’ the White House said.

Obama wants the initial $100 million investment to support research at the National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation. He also wants private companies, universities and philanthropists to partner with the federal agencies in support of the research. And he wants a study of the ethical, legal and societal implications of the research.

The goals of the work are unclear at this point. A working group at NIH, co-chaired by Cornelia ‘‘Cori’’ Bargmann of The Rockefeller University and William Newsome of Stanford University, would work on defining the goals and develop a multi-year plan to achieve them that included cost estimates.

Forget about plaque when diagnosing Alzheimer’s Disease

An Australian study has shown that plaque, long considered to be the hallmark of Alzheimer’s disease, is one of the last events to occur in the Alzheimer’s brain. This finding will impact the current debate about how best to diagnose and treat Alzheimer’s disease.

PhD student Amanda Wright and Dr Bryce Vissel from Sydney’s Garvan Institute of Medical Research studied a mouse model of Alzheimer’s disease in order to identify early versus late disease mechanisms and markers.

The data, published online today in the journal PLOS ONE, suggest that plaques occur long after memory loss, so may not be a useful early pathological marker for Alzheimer’s disease.

The Investigators found that significant nerve cell loss and a range of brain pathologies, including inflammation, began at the same time as subtle memory problems appeared, early in the disease process. Plaques occurred much later, well after significant memory loss.

“Ever since Alois Alzheimer first described this disease in 1906, plaque has been regarded as the definitive Alzheimer’s diagnosis,” said project leader Dr Vissel.

“Just last year, the first ever method of plaque detection through positron emission tomography (PET) was introduced into the clinic to assist in the diagnosis of Alzheimer’s disease – precisely because plaque is regarded as the conclusive marker for Alzheimer’s disease. Our study suggests that this method may not be accurate in earlier disease stages.”

Dr Vissel said that many billions of dollars have been spent around the world in trying to develop markers and drugs to block the development of plaque. Several drug trials based on this idea have failed recently.

“Our study supports the increasingly common view that treatment should start much earlier in the disease process. It also suggests that brain inflammation and cell loss may be an earlier indicator of disease pathology than plaque and an alternative target for treatment.”

“In addition, what’s coming out in various studies is that mild cognitive impairment may be another early predictor of Alzheimer’s. This seems to fit perfectly with our findings, which show mild memory loss and behavioural changes at an early stage before plaque appears.”

“I can see that the development of some clever learning and language tests to test for early signs of cognitive impairment will be an important indicator of dementia, when combined with a range of yet to be developed tests.”

(Image: Getty Images)

Personalized Brain Mapping Technique Preserves Function Following Brain Tumor Surgery

Neurosurgeons can visualize important pathways in the brain using an imaging technique called diffusion tensor imaging (DTI), to better adapt brain tumor surgeries and preserve language, visual and motor function while removing cancerous tissue. In the latest issue of Neurosurgical Focus, researchers from the Perelman School of Medicine at the University of Pennsylvania review research showing that this ability to visualize relevant white matter tracts during glioma resection surgeries can improve accuracy and, in some groups, significantly extend survival (median survival of 21.2 months) compared to cases where DTI was not used  (median survival of 14 months).

"We can view the brain from the inside out now, with 3D images detailing connectivity within the brain, making a virtual intraoperative map," said senior author Steven Brem, MD, professor of Neurosurgery, chief of the Division of Neurosurgical Oncology and co-director of the Penn Brain Tumor Center. "Penn is at the forefront of a major shift in the field - we now have such detail about each individual’s brain tumor - combining diffusion tensor imaging and advanced imaging with the entire personalized diagnostics analysis available for all brain tumor patients at Penn Medicine."

Diffusion tensor imaging (DTI) provides a rendering of axon pathways, by tracking water molecules in the brain as they travel in a direction parallel to axonal fibers, in a 3D model known as “the diffusion tensor.” The diffusion tensor directly represents the direction of water and indirectly represents the orientation of white matter fibers. The colorful images, captured as part of an 8 minute sequence during an MRI, show representations of clusters of axon fibers, where each color indicates a direction of travel, and offer a glimpse of the interwoven communication superhighways of the brain.

"The DTI images can be overlaid with structural and functional MRI images, providing a hybrid map showing topography layered with a road map," said Neurosurgery resident Kalil Abdullah, MD, lead author of the paper. "This rendering gives us increased clarity to visualize important white matter tracts in the brain and adapt our surgical approaches to each person’s case. Rather than focusing on solely taking the tumor out, we can avoid damage to healthy tissue and preserve important pathways responsible for speech, vision and motor function."

Relying heavily on the expertise of radiologists who process and analyze the DTI images, including Ronald L. Wolf, MD, PhD, associate professor of Radiology at Penn, the research on DTI is being translated into clinical practice to guide surgical procedures. Further research efforts are targeted at defining language deficits before surgery and following-up post-operatively to determine any changes or improvements following treatment based on the use of DTI.

Working collaboratively with colleagues in Penn’s departments of Neurosurgery, Neurology, Radiology, Radiation Oncology, Nursing, Pathology and Laboratory Medicine and the Abramson Cancer Center, the Penn Brain Tumor Center combines the latest imaging, biomarker and genetic tumor testing to provide a personalized treatment plan for all types of brain cancers. Brain tumors are among the first areas of interest for Penn’s Center for Personalized Diagnostics (CPD), a joint initiative by Penn Medicine’s Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, which integrates Molecular Genetics, Pathology Informatics, and Genomic Pathology for individualized patient diagnoses and to elucidate cancer treatment options for physicians.

(Image: Swedish Research)

New Research on the Effects of Traumatic Brain Injury (TBI)

Considerable opportunity exists to improve interventions and outcomes of traumatic brain injury (TBI) in older adults, according to three studies published in the recent online issue of NeuroRehabilitation by researchers from the Icahn School of Medicine at Mount Sinai.

An Exploration of Clinical Dementia Phenotypes Among Individuals With and Without Traumatic Brain Injury

Some evidence suggests that a history of TBI is associated with an increased risk of dementia later in life, but the clinical features of dementia associated with TBI have not been well investigated.  Researchers at the Icahn School of Medicine as well as other institutions analyzed data from elderly individuals with dementia with and without a history of TBI to characterize the clinical profiles of patients with post-TBI dementia.

The results of the study indicate that compared to older adults with dementia with no history of TBI, those with a history of TBI had higher fluency and verbal memory scores and later onset of decline. However, their general health was worse, they were more likely to have received medical attention for depression, and were more likely to have a gait disorder, falls, and motor slowness.  These findings suggest that dementia among individuals with a history of TBI may represent a unique clinical phenotype that is distinct from that seen among elderly individuals who develop dementia without a history of TBI.

"Our study indicates that individuals with dementia and without a history of TBI may present clinical characteristics that differ in subtle but meaningful ways," said Kristen Dams-O’Connor, PhD, first author of the study and an Assistant Professor of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai. "It is imperative that clinicians take a history of TBI into account when making dementia diagnoses."

For this study, researchers used data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) collected between September 2005 and May 2012 to analyze 332 elderly individuals with dementia and a history of TBI and 664 elderly individuals without dementia who do have a history of TBI. Statistical analyses focused on evaluating differences in the areas of neurocognitive functioning, psychiatric functioning, medical history and health, clinical characteristics of dementia, and dementia diagnosis using data collected at the baseline (first) NACC study visit.

Mortality of Elderly Individuals with TBI in the First 5 Years Following Injury

After observing a high rate of mortality among patients over the age of 55 in the first five years after sustaining a TBI, researchers at the Icahn School of Medicine at Mount Sinai were interested in learning more about the precise causes for what may be considered a premature death.

The results of this study indicate that for approximately a third of the patients, death one to five years after TBI resulted from health conditions that were present at the time of injury before the onset of TBI, suggesting a continuation of an already ongoing process. The remainder of patients died from conditions that appeared to unfold in the years after injury. According to the authors, each cause of death in this sample would have required pro-active medical management, medical intervention and medication compliance.

"Like those with other chronic health conditions, individuals with TBI could benefit from the development of a disease management model of primary care," said one of the study authors, Wayne Gordon, PhD, Jack Nash Professor and Vice Chair of the Department of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai and Chief of the Rehabilitation Psychology and Neuropsychology service. "This study suggests that close medical management and lifestyle interventions may help to prevent premature death among elderly survivors of TBI in the future."

Researchers reviewed the charts of 30 individuals over the age of 55 who completed inpatient acute rehabilitation during the period from 2003-2009 and who died one to four years after TBI, and then compared that data to a matched sample of 30 patients who did not die. They found that 53 percent of deceased subjects had been diagnosed with gait abnormalities, 32 percent were taking respiratory medications at admission, and 17 percent were taking respiratory medications at discharge. Compared to patients who survived several years after injury, deceased patients were discharged from the hospital with significantly more medications.

Inpatient Rehabilitation for Traumatic Brain Injury: The Influence of Age on Treatments and Outcomes

For this study, researchers analyzed the difference in treatment and outcomes between elderly and younger patients with TBI. They found that patients over 65 had lower brain injury severity and a shorter length of stay in acute care. Elderly patients also received fewer hours of rehabilitation therapy, due to a shorter length of stay, and fewer hours of treatment per day, especially from psychology and therapeutic recreation. They gained less functional ability during and after rehabilitation, and had a very high mortality rate.

"We know significantly more about the treatment received by adolescents and young adults with TBI than we do about those over 65," said Marcel Dijkers, PhD, lead author and Research Professor in the Department of Rehabilitation Medicine at Mount Sinai.  "Our data indicates that elderly people can be rehabilitated successfully, but it raises a number of questions. For instance: is the high mortality due to the TBI or is it the result of the continuation of a condition that began pre-TBI?"

The researchers analyzed data on 1,419 patients with TBI admitted to nine TBI rehabilitation inpatient programs across the country between 2009 and 2011. They collected data through abstracting of medical records, point-of-care forms completed by therapists, and interviews conducted three and nine months after discharge.

Which Came First, the Head or the Brain?

The sea anemone, a cnidarian, has no brain. It does have a nervous system, and its body has a clear axis, with a mouth on one side and a basal disk on the other. However, there is no organized collection of neurons comparable to the kind of brain found in bilaterians, animals that have both a bilateral symmetry and a top and bottom. (Most animals except sponges, cnidarians, and a few other phyla are bilaterians.) So an interesting evolutionary question is, which came first, the head or the brain? Do animals such as sea anemones, which lack a brain, have something akin to a head?

In this issue of PLOS Biology, Chiara Sinigaglia and colleagues report that at least some developmental pathways seen in cnidarians share a common lineage with head and brain development in bilaterians. It might seem intuitive to expect to find genes involved in brain development around the mouth of the anemone, and previous work has suggested that the oral region in cnidarians corresponds to the head region of bilaterians. However, there has been debate over whether the oral or aboral pole of cnidarians is analogous to the anterior pole of bilaterians. At the start of its life cycle a sea anemone exists as a free swimming planula, which then attaches to a surface and becomes a sea anemone. That free-swimming phase contains an apical tuft, a sensory structure at the front of the swimming animal’s body. The apical tuft is the part that attaches and becomes the aboral pole (the part distal from the mouth) of the adult anemone.

To test whether genetic expression in the aboral pole of cnidarians does in fact resemble the head patterning seen in bilaterians, the researchers analyzed gene expression in Nematostella vectensis, a sea anemone found in estuaries and bays. They focused on the six3 and FoxQ2 transcription factors, as these genes are known to regulate development of the anterior-posterior axis in bilaterian species. (six3 knockout mice, for example, fail to develop a forebrain, and in humans, six3 is known to regulate the development of forebrain and eyes.)

The N. vectensis genome contains one gene from the six3/6 group and four foxQ2 genes. Sinigaglia and colleagues found that Nvsix3/6 and one of the foxQ2 genes, NvFoxQ2a, were expressed predominantly on the aboral pole of the developing cnidarian but, after gastrulation, were excluded from a small spot in that region (NvSix3/6 was also expressed in a small number of other cells of the planula that resembled neurons). Because of this, the authors call NvSix3/6 and NvFoQ2a “ring genes”, and genes that are then expressed in that spot “spot genes.” The spot then develops into the apical tuft.

Through knockdown and rescue experiments, the researchers demonstrate that NvSix3/6 is required for the development of the aboral region; without it, the expression of spot genes is reduced or eliminated and the apical tuft of the planula doesn’t form. This suggests that development of the region distal from the cnidarian mouth appears to parallel the development of the bilaterian head.

This research demonstrates that at least a subset of the genes that cause head and brain formation in bilaterians are also differentially expressed in the aboral region of the sea urchin. The expression patterns are not identical to those in all bilaterians; however, the similarities suggest that the patterns of gene expression arose in an ancestor common to bilaterians and cnidarians, and that the process was then modified in bilaterians to produce a brain. So to answer the evolutionary question posed above, it seems that the developmental module that produces a head came first.

Is Obama’s Plan to Map the Human Brain this Generation’s Equivalent to Landing a Man on the Moon?

President John F. Kennedy’s mission in the 1960s was to land a man on the moon. President Bill Clinton made cracking the human genome one of his top priorities. Now, President Barack Obama says a detailed map of the human brain is necessary to understand how it works and what needs to be done when it’s not working properly. The president is expected to unveil his plans for an estimated $3 billion, decade-long commitment to the Brain Activity Map project next month in his 2014 budget proposal.

Rutgers Today talked with Rutgers University behavioral neuroscientist Timothy Otto, professor and director of the Behavioral and Systems Neuroscience program in the Department of Psychology, about what we know about the brain, how much we still need to discover and if spending billions of dollars in research will enable scientists to develop new treatments for debilitating neurological diseases like Alzheimer’s, Parkinson’s and autism.

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Rats’ brains are more like ours than scientists previously thought

Neuroscientists face a multitude of challenges in their efforts to better understand the human brain. If not for model organisms such as the rat, they might never know what really goes on inside our heads.

The brain is a phenomenal processor that in a year’s time can generate roughly 300,000 petabytes of data — 30,000 times the amount generated by the Large Hadron Collider. Trying to decipher its signals is a daunting prospect.

But particularly for individuals who have lost a limb or been partially or fully paralyzed, such research has potentially life-changing results because it can enable such biotechnological advances as the development of a brain-computer interface for controlling prosthetic limbs.

Such devices require a detailed understanding of the motor cortex, a part of the brain that is crucial in issuing the neural commands that execute behavioral movements. A recent paper published in the journal Frontiers in Neural Circuits by Jared Smith and Kevin Alloway, researchers at the Penn State Center for Neural Engineering and affiliates of the Huck Institutes of the Life Sciences, details their discovery of a parallel between the motor cortices of rats and humans that signifies a greater relevance of the rat model to studies of the human brain than scientists had previously known.

"The motor cortex in primates is subdivided into multiple regions, each of which receives unique inputs that allow it to perform a specific motor function," said Alloway, professor of neural and behavioral sciences. "In the rat brain, the motor cortex is small and it appeared that all of it received the same type of input. We know now that sensory inputs to the rat motor cortex terminate in a small region of the motor cortex that is distinct from the larger region that issues the motor commands. Our work demonstrates that the rat motor cortex is parcellated into distinct subregions that perform specific functions, and this result appears to be similar to what is seen in the primate brain."

"You have to take into account the animal’s natural behaviors to best understand how its brain is structured for sensory and motor processing," said Jared Smith, graduate student in the Huck Institutes’ neuroscience program and the first author of the paper. "For primates like us, that means a strong reliance on visual information from the eyes, but for rats it’s more about the somatosensory inputs from their whiskers."

In fact, nearly a third of the rat’s sensorimotor cortex is devoted to processing whisker-related information, even though the whiskers’ occupy only one-third of one percent of the rat’s total body surface. In humans, nearly 40 percent of the entire cortex is devoted to processing visual information even though the eyes occupy a very tiny portion of our body’s surface.

To understand the structure and function of the rat motor cortex, Smith and Alloway conducted a series of experiments focused on the medial agranular region, which responds to whisker stimulation and elicits whisker movements when stimulated.

"Our research," said Smith, "was conducted in two stages to investigate the functional organization of the brain: first tracing the neuronal connectivity, and then measuring how the circuits behave in terms of their electrophysiology. Just like in any electrical circuit, the first thing you need to do is trace the wires to see how the different components are connected. Then you can use this information to make sense of the activity going on at any particular node. In the end, you can step back and see how all the circuits work together to achieve something more complex, such as motor control."

"We discovered different sensory input regions that were distinct from the region that issued the motor commands to move the whiskers," said Alloway. "In this respect, we were fortunate to have Patrick Drew [assistant professor of engineering science and mechanics and neurosurgery at Penn State] help us analyze the EMG signals produced by microstimulation because this showed that the sensory input region was significantly less effective in evoking whisker movements."

As a result of Smith and Alloway’s discovery, previously published data on the rat motor cortex can be revisited with a new degree of specificity, and more similarities between the brains and neural processes of rats and humans may eventually come to light, perhaps even informing studies of other model organisms. This discovery is also likely to advance the study of the human brain.

"This study opens up avenues for studying some very complex neural processes in rodents that are more like our own than we had previously thought," said Smith. "The tools now available for studying activity in the rodent brain are improving at a remarkable pace, and the findings are even more interesting as we discover just how similar these mammalian relatives are to us. This is a very exciting time in neuroscience."