Robot Allows ‘Remote Presence’ in Programming Brain and Spine Stimulators

With the rapidly expanding use of brain and spinal cord stimulation therapy (neuromodulation), new “remote presence” technologies may help to meet the demand for experts to perform stimulator programming, reports a study in the January issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The preliminary study by Dr. Ivar Mendez of Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, Canada, supports the feasibility and safety of using a remote presence robot—called the “RP-7”—to increase access to specialists qualified to program the brain and spine stimulators used in neuromodulation.

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Light Switch Inside Brain: Laser Controls Individual Nerve Cells in Mouse

Activating and deactivating individual nerve cells in the brain is something many neuroscientists wish they could do, as it would help them to better understand how the brain works.

Scientists in Freiburg and Basel, Switzerland, have developed an implant that is able to genetically modify specific nerve cells, control them with light stimuli, and measure their electrical activity all at the same time. This novel 3-in-1 tool paves the way for completely new experiments in neurobiology, also at Freiburg’s new Cluster of Excellence BrainLinks-BrainTools.

Birthe Rubehn and her colleagues from the Department of Microsystems Engineering (IMTEK) and the Bernstein Center of the University of Freiburg as well as the Friedrich Miescher Institute for Biomedical Research in Basel describe the prototype of their implant in the journal Lab on a Chip. They report that initial experiments in which they implanted prototypes into mice were successful: The team was able to influence the activity of nerve cells in the brain in a controlled manner by means of laser light pulses.

The team used an innovative genetic technique that makes nerve cells change their activity by shining different colored lights on them. In optogenetics, genes from certain species of algae are inserted into the genome of another organism, for instance a mouse. The genes lead to the inclusion of light-sensitive pores for electrically charged particles into a nerve cell’s membrane. These additional openings allow neuroscientists to control the cells’ electrical activity.

However, only the new implant from Freiburg and Basel makes this principle actually practicable. The device, at its tip only a quarter of a millimeter wide and a tenth of a millimeter thick, was constructed on the basis of polymers, special plastics whose safety for implantation into the nervous system has been proven.

Unlike probes developed so far, it is capable of injecting substances necessary for genetic modification, emitting light for the stimulation of the nerve cells, and measuring the effect through various electrical contacts all at once. Besides optimizing the technique for production, the scientists want to develop a second version whose injection channel dissolves over time, reducing the implant’s size even further.

Study findings have potential to prevent, reverse serious disabilities affecting children born prematurely

Physician-scientists at Oregon Health & Science University Doernbecher Children’s Hospital are challenging the way pediatric neurologists think about brain injury in the pre-term infant. In a study published online in the Jan. 16 issue of Science Translational Medicine, the OHSU Doernbecher researchers report for the first time that low blood and oxygen flow to the developing brain does not, as previously thought, cause an irreversible loss of brain cells, but rather disrupts the cells’ ability to fully mature. This discovery opens up new avenues for potential therapies to promote regeneration and repair of the premature brain.

“As neurologists, we thought ischemia killed the neurons and that they were irreversibly lost from the brain. But this new data challenges that notion by showing that ischemia, or low blood flow to the brain, can alter the maturation of the neurons without causing the death of these cells. As a result, we can focus greater attention on developing the right interventions, at the right time early in development, to promote neurons to more fully mature and reduce the often serious impact of preterm birth. We now have a much more hopeful scenario,” said Stephen Back, M.D., Ph.D., lead investigator and professor of pediatrics and neurology in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital.

Researchers at OHSU Doernbecher have conducted a number of studies in preterm fetal sheep to define how disturbances in brain blood flow lead to injury in the developing brain. Their findings have led to important advances in the care of critically ill newborn infants.

For this study, Back and colleagues used pioneering new MRI studies that allow injury to the developing brain to be identified much earlier than previously feasible. They looked at the cerebral cortex, or “thinking” part of the brain, which controls the complex tasks involved with learning, attention and social behaviors that are frequently impaired in children who survive preterm birth. Specifically, they observed how brain injury in the cerebral cortex of fetal sheep evolved over one month and found no evidence that cells were dying or being lost. They did notice, however, that more brain cells were packed into a smaller volume of brain tissue, which led to, upon further examination, the discovery that the brain cells weren’t fully mature.

In a related study published in the same online issue of Science Translational Medicine, investigators at The Hospital for Sick Children and the University of Toronto studied 95 premature infants using MRI and found that impaired growth of the infants was the strongest predictor of the MRI abnormalities, suggesting that interventions to improve infant nutrition and growth may lead to improved cortical development.

“I believe these studies provide hope for the future for preterm babies with brain injury, because our findings suggest that neurons are not being permanently lost from the human cerebral cortex due to ischemia. This raises the possibility that neurodevelopmental enrichment — or perhaps improved early infant nutrition — as suggested by the companion paper, might make a difference in terms of improved cognitive outcome,” Back said.

“Together, these studies challenge the conventional wisdom that preterm birth is associated with a loss of cortical neurons. This finding may change the way neurologists think about diagnosing and treating children born prematurely,” said Jill Morris, Ph.D., a program director at the National Institute’s of Health’s National Institute Neurological Disorders and Stroke.

How the brain copes with multi-tasking alters with age

The pattern of blood flow in the prefrontal cortex in the brains alters with age during multi-tasking, finds a new study in BioMed Central’s open access journal BMC Neuroscience. Increased blood volume, measured using oxygenated haemoglobin (Oxy-Hb) increased at the start of multitasking in all age groups. But to perform the same tasks, healthy older people had a higher and more sustained increase in Oxy-Hb than younger people.

Age related changes to the brain occur earliest in the prefrontal cortex, the area of the brain associated with memory, emotion, and higher decision making functions. It is changes to this area of the brain that are also associated with dementia, depression and other neuropsychiatric disorders. Some studies have shown that regular physical activity and cognitive training can prevent cognitive decline (use it or lose it!) but to establish what occurs in a healthy aging brain researchers from Japan and USA have compared brain activity during single and dual tasks for young (aged 21 to 25) and older (over 65) people.

Near infrared spectroscopy (NIRS) measurements of Oxy-Hb showed that blood flow to the prefrontal cortex was not affected by the physical task for either age group but was affected by the mental task. For both the young and the over 65s the start of the calculation task  coincided with an increase in blood volume which reduced to baseline once the task was completed.

The main difference between the groups was only seen when performing the physical and mental tasks at the same time - older people had a higher prefrontal cortex response which lasted longer than the younger group.

Hironori Ohsugi, from Seirei Christopher University, and one of the team who performed this research explained “From our observations during the dual task it seems that the older people turn their attention to the calculation at the expense of the physical task, while younger people are able to maintain concentration on both. Since our subjects were all healthy it seems that this requirement for increased activation of the prefrontal cortex is part of normal decrease in brain function associated with aging. Further study will show whether or not dual task training can be used to maintain a more youthful brain.”

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Is Athleticism Linked to Brain Size?

To find out, researchers at the University of California, Riverside performed laboratory experiments on house mice and found that mice that have been bred for dozens of generations to be more exercise-loving have larger midbrains than those that have not been selectively bred this way.

Theodore Garland’s lab measured the brain mass of these uniquely athletic house mice, bred for high voluntary wheel-running, and analyzed their high-resolution brain images. The researchers found that the volume of the midbrain — a small region of the brain that relays information for the visual, auditory, and motor systems — in the bred-for-athleticism mice was nearly 13 percent larger than the midbrain volume in the control or “regular” mice.

“To our knowledge, this is the first example in which selection for a particular mammalian behavior — high voluntary wheel running in house mice in our set of experiments — has been shown to result in a change in size of a specific brain region,” said Garland, a professor of biology and the principal investigator of the research project.

Study results appeared online Jan. 16 in The Journal of Experimental Biology

Individuals with a low risk for cocaine dependence have a differently shaped brain to those with addiction

People who take cocaine over many years without becoming addicted have a brain structure which is significantly different from those individuals who developed cocaine-dependence, researchers have discovered. New research from the University of Cambridge has found that recreational drug users who have not developed a dependence have an abnormally large frontal lobe, the section of the brain implicated in self-control. Their research was published in the journal Biological Psychiatry.

For the study, led by Dr Karen Ersche, individuals who use cocaine on a regular basis underwent a brain scan and completed a series of personality tests. The majority of the cocaine users were addicted to the drug but some were not (despite having used it for several years).

The scientists discovered that a region in the frontal lobes of the brain, known to be critically implicated in decision-making and self-control, was abnormally bigger in the recreational cocaine users. The Cambridge researchers suggest that this abnormal increase in grey matter volume, which they believe predates drug use, might reflect resilience to the effects of cocaine, and even possibly helps these recreational cocaine users to exert self-control and to make advantageous decisions which minimize the risk of them becoming addicted.

They found that this same region in the frontal lobes of the brain was significantly reduced in size in people with cocaine dependence, confirming earlier research that had found similar results. They believe that at least some of these changes are the result of drug use, which causes drug users to lose grey matter.

They also found that people who use illicit drugs like cocaine exhibit high levels of sensation-seeking personality traits, but only those developing dependence show personality traits of impulsivity and compulsivity.

Dr Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the University of Cambridge, said: “These findings are important because they show that the use of cocaine does not inevitably lead to addiction in people with good self-control and no familial risk.

“Our findings indicate that preventative strategies might be more effective if they were tailored more closely to those individuals at risk according to their personality profile and brain structure.”

The researchers will next explore the basis of the recreational users’ apparent resilience to drug dependence. Dr Ersche added: “Their high level of education, less troubled family background or the beginning of drug-taking only after puberty may all play a role.”

Mouse Research Links Adolescent Stress and Severe Adult Mental Illness

Working with mice, Johns Hopkins researchers have established a link between elevated levels of a stress hormone in adolescence - a critical time for brain development - and genetic changes that, in young adulthood, cause severe mental illness in those predisposed to it.

The findings, reported in the journal Science, could have wide-reaching implications in both the prevention and treatment of schizophrenia, severe depression and other mental illnesses.

"We have discovered a mechanism for how environmental factors, such as stress hormones, can affect the brain’s physiology and bring about mental illness," says study leader Akira Sawa, M.D., Ph.D., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We’ve shown in mice that stress in adolescence can affect the expression of a gene that codes for a key neurotransmitter related to mental function and psychiatric illness. While many genes are believed to be involved in the development of mental illness, my gut feeling is environmental factors are critically important to the process."

Sawa, director of the Johns Hopkins Schizophrenia Center, and his team set out to simulate social isolation associated with the difficult years of adolescents in human teens. They found that isolating healthy mice from other mice for three weeks during the equivalent of rodent adolescence had no effect on their behavior. But, when mice known to have a genetic predisposition to characteristics of mental illness were similarly isolated, they exhibited behaviors associated with mental illness, such as hyperactivity. They also failed to swim when put in a pool, an indirect correlate of human depression. When the isolated mice with genetic risk factors for mental illness were returned to group housing with other mice, they continued to exhibit these abnormal behaviors, a finding that suggests the effects of isolation lasted into the equivalent of adulthood.

"Genetic risk factors in these experiments were necessary, but not sufficient, to cause behaviors associated with mental illness in mice," Sawa says. "Only the addition of the external stressor - in this case, excess cortisol related to social isolation - was enough to bring about dramatic behavior changes."

The investigators not only found that the “mentally ill” mice had elevated levels of cortisol, known as the stress hormone because it’s secreted in higher levels during the body’s fight-or-flight response. They also found that these mice had significantly lower levels of the neurotransmitter dopamine in a specific region of the brain involved in higher brain function, such as emotional control and cognition. Changes in dopamine in the brains of patients with schizophrenia, depression and mood disorders have been suggested in clinical studies, but the mechanism for the clinical impact remains elusive.

Light Exposure During Pregnancy Key to Normal Eye Development

New research in Nature concludes the eye – which depends on light to see – also needs light to develop normally during pregnancy.

Scientists say the unexpected finding offers a new basic understanding of fetal eye development and ocular diseases caused by vascular disorders – in particular one called retinopathy of prematurity that can blind premature infants. The research, led by scientists at Cincinnati Children’s Hospital Medical Center and the University of California, San Francisco (UCSF), appears online Jan. 16 ahead of print publication.

“This fundamentally changes our understanding of how the retina develops,” says study co-author Richard Lang, PhD, a researcher in the Division of Pediatric Ophthalmology at Cincinnati Children’s Hospital Medical Center. “We have identified a light-response pathway that controls the number of retinal neurons. This has downstream effects on developing vasculature in the eye and is important because several major eye diseases are vascular diseases.”

Lang is a principal investigator on the ongoing research along with project collaborator, David Copenhagen, PhD, a scientist in the departments of Ophthalmology and Physiology at UCSF. The scientists say their current study, conducted in mouse models, includes several unexpected findings.

"Several stages of mouse eye development occur after birth," says Copenhagen. "Because of this, we had always assumed that if light played a role in the development of the eye, it would also happen only after birth."

But researchers in the current study found that activation of the newly described light-response pathway must happen during pregnancy to activate the carefully choreographed program that produces a healthy eye. Specifically, they say it is important for a sufficient number of photons to enter the mother’s body by late gestation, or about 16 days into a mouse pregnancy.

Researchers were also surprised to learn that photons of light activate a protein called melanopsin directly in the fetus – not the mother – to help initiate normal development of blood vessels and retinal neurons in the eye.

One purpose of the light-response pathway is to suppress the number of blood vessels that form in the retina. These vessels are critical to retinal neurons, which require large amounts of oxygen to form and to function. When retinopathy of prematurity occurs in infants, retinal vessels grow almost unchecked. This continued expansion puts intense pressure on the developing eye and in extreme cases causes severe damage and blindness.

The research team led by Lang and Copenhagen conducted several experiments in laboratory mouse models that allowed them to identify the light-response pathway’s specific components and function.

Mice were reared in the dark and in a normal day-night cycle beginning at late gestation to observe the comparative effects on vascular development of the eye. The researchers verified the function of the light response pathway by mutating an opsin gene in mice called Opn4 that produces melanopsin, in essence preventing activation of the photo pigment.

Both mice reared under dark conditions from late gestation, and those with mutated Opn4, exhibited nearly identical promiscuous expansion of hyaloid vessels and abnormal retinal vascular growth. The unchecked vascular growth was driven by the protein vascular endothelial growth factor (Vegfa). When the light response pathway is properly engaged, it modulates Vegfa to help prevent promiscuous vascular growth, according to researchers.

The melanopsin protein is present in both mice and humans during pregnancy. Lang said the research team is continuing to study how the light-response pathway might influence the susceptibility of pre-term infants to retinopathy of prematurity and also be related to other diseases of the eye.

New research finds slower growth of preterm infants linked to altered brain development

Preterm infants who grow more slowly as they approached what would have been their due dates also have slower development in an area of the brain called the cerebral cortex, report Canadian researchers in a new study published in Science Translational Medicine.

The cerebral cortex is a two to four millimetre layer of cells that envelopes the top part of the brain and is involved in cognitive, behavioural, and motor processes.

Researchers analyzed MRI brain scans of 95 preterm infants born eight to 16 weeks too early at BC Women’s Hospital & Health Centre between 2006 and 2009. Infants were scanned soon after birth and a second time close to what would have been their due date, the ninth month of pregnancy. These MRI scans allowed researchers to measure the pattern of water movement inside the brain, which normally changes between scans as the brain matures. The researchers also assessed the babies’ weight, length, and head size. They found that preterm infants with slower growth had delayed development in the cerebral cortex compared to those infants who grew more quickly between scans.

“These results are an exciting first step because understanding the importance of growth in relation to the brain in these small babies may eventually lead to new discoveries that will help us optimize their brain development,” says Dr. Steven Miller, the study’s co‐lead. Dr. Miller is head of neurology at The Hospital for Sick Children (SickKids), the Bloorview Children’s Hospital Chair in Paediatric Neuroscience, professor in the department of Paediatrics at the University of Toronto, affiliate professor in the department of Pediatrics at the University of British Columbia (UBC), and affiliate investigator at the Child & Family Research Institute (CFRI) at BC Children’s Hospital. He led the study with Dr. Ruth Grunau, a professor in the UBC Department of Pediatrics and CFRI senior scientist.

“More research needs to be done to understand what is the optimal growth rate for the brain development of these babies,” says Jillian Vinall, the study’s first author and a UBC PhD student cosupervised by Dr. Grunau and Dr. Miller.

We’re especially grateful to the families for their generous and ongoing participation in this study,” says Dr. Miller. The researchers are following the babies through childhood to understand how preterm brain development is associated with their neurodevelopment outcomes.