Johns Hopkins Surgeons Implant First Brain ‘Pacemaker’ for Alzheimer’s Disease in United States as Part of a Clinical Trial Designed to Slow Memory Loss

Researchers at Johns Hopkins Medicine in November surgically implanted a pacemaker-like device into the brain of a patient in the early stages of Alzheimer’s disease, the first such operation in the United States. The device, which provides deep brain stimulation and has been used in thousands of people with Parkinson’s disease, is seen as a possible means of boosting memory and reversing cognitive decline.

The surgery is part of a federally funded, multicenter clinical trial marking a new direction in clinical research designed to slow or halt the ravages of the disease, which slowly robs its mostly elderly victims of a lifetime of memories and the ability to perform the simplest of daily tasks, researchers at Johns Hopkins say. Instead of focusing on drug treatments, many of which have failed in recent clinical trials, the research focuses on the use of the low-voltage electrical charges delivered directly to the brain. There is no cure for Alzheimer’s disease.

As part of a preliminary safety study in 2010, the devices were implanted in six Alzheimer’s disease patients in Canada. Researchers found that patients with mild forms of the disorder showed sustained increases in glucose metabolism, an indicator of neuronal activity, over a 13-month period. Most Alzheimer’s disease patients show decreases in glucose metabolism over the same period.

The first U.S. patient in the new trial underwent surgery at The Johns Hopkins Hospital, and a second patient is scheduled for the same procedure in December. The surgeries at Johns Hopkins are being performed by neurosurgeon William S. Anderson, M.D.

The surgery involves drilling holes into the skull to implant wires into the fornix on either side of the brain. The fornix is a brain pathway instrumental in bringing information to the hippocampus, the portion of the brain where learning begins and memories are made, and where the earliest symptoms of Alzheimer’s appear to arise. The wires are attached to a pacemaker-like device, the “stimulator,” which generates tiny electrical impulses into the brain 130 times a second. The patients don’t feel the current, says Paul B. Rosenberg, M.D., an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and site director of the trial’s Johns Hopkins location. 

Mammalian brain knows where it’s at

A new study in the journal Neuron suggests that the brain uses a different region than neuroscientists had thought to associate objects and locations in the space around an individual. Knowing where this fundamental process occurs could help treat disease and brain injury as well as inform basic understanding of how the brain supports memory and guides behavior.

“Understanding how and where context is represented in the brain is important,” said study senior author Rebecca Burwell, professor of psychology and neuroscience at Brown University. “Context, or the place in which events occur, is the hallmark of episodic memory, but context is more than a place or a location. This room, for example, has a window, furniture, and other objects. You walk into a room and all that information helps you remember what happened there.”

Pinpointing where the brain puts together objects and places to form a context could also matter for treating traumatic brain injuries or neuropsychiatric diseases, such as schizophrenia and depression, that involve that part of the brain, said Burwell, who is also affiliated with the Brown Institute for Brain Science.

“We know that contextual representations are disrupted in mental disorders, particularly schizophrenia and depression,” Burwell said. “Individuals with these disorders have trouble using context to plan actions or choose appropriate behaviors.”

After 100 Years, Understanding the Electrical Role of Dendritic Spines

It’s the least understood organ in the human body: the brain, a massive network of electrically excitable neurons, all communicating with one another via receptors on their tree-like dendrites. Somehow these cells work together to enable great feats of human learning and memory. But how?

Researchers know dendritic spines play a vital role. These tiny membranous structures protrude from dendrites’ branches; spread across the entire dendritic tree, the spines on one neuron collect signals from an average of 1,000 others. But more than a century after they were discovered, their function still remains only partially understood.

A Northwestern University researcher, working in collaboration with scientists at the Howard Hughes Medical Institute (HHMI) Janelia Farm Research Campus, has recently added an important piece of the puzzle of how neurons “talk” to one another. The researchers have demonstrated that spines serve as electrical compartments in the neuron, isolating and amplifying electrical signals received at the synapses, the sites at which neurons connect to one another.

The key to this discovery is the result of innovative experiments at the Janelia Farm Research Campus and computer simulations performed at Northwestern University that can measure electrical responses on spines throughout the dendrites.

A paper about the findings, “Synaptic Amplification by Dendritic Spines Enhances Input Cooperatively,” was published November 22 in the journal Nature.

“This research conclusively shows that dendritic spines respond to and process synaptic inputs not just chemically, but also electrically,” said William Kath, professor of engineering sciences and applied mathematics at Northwestern’s McCormick School of Engineering, professor of neurobiology at the Weinberg College of Arts and Sciences, and one of the paper’s authors.

Electronic brain hacks are turning insects into robotic helpers

We’re a long way from directly controlling human minds remotely, but recent years have seen a string of breakthroughs in hacking the minds of insects. Insect brains are probably the simplest interesting brains, as insects can perform a range of tasks (flying, smelling, carrying, etc.) with brains that have numbers of neurons orders of magnitude less than those in complex vertebrates. A fruit fly has around 100,00 neurons, compared to 85 billion in humans.

So at the conjunction of neuroscience and robotics lie insects — their tiny brains still too complex to model completely, but offering an easy way into modelling certain parts of the brain. It’s how engineers from Sheffield and Sussex universities can claim they’re preparing to upload the smell and sight parts of a bee’s brain into a bee-like flying robot, enmeshed with human-created software to create a completely new “brain”.

The hope is that the bee-bot could fly in areas that other robots can’t fit, like a collapsed building. And it makes sense to use nature’s own smell modules instead of developing new ones — their combination of efficiency in size and operation is so far unmatched by anything synthetic. A bee-bot could smell out explosives in a warzone, or drugs in shipping containers, or any of many other myriad uses, and actually go investigate. They can even be used as little spies. Who would notice a fly sitting on the wall of a meeting room?

A lot of research in the area of bug brains is being funded by the US Defense Advanced Research Projects Agency (Darpa), the Pentagon agency which seeks out new technologies for military use. It’s not hard to imagine a future where drones are grown on farms, with extra controls implanted at the larval stage — a process developed by bionic researchers at North Carolina State University.

Lipid metabolism regulates the activity of adult neural stem cells

Neural stem cells generate thousands of new neurons every day in two regions of the adult brain: the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus. This process, called adult neurogenesis, is critical for a number of processes implicated in certain forms of learning and memory. Impaired adult neurogenesis has been associated with a number of diseases such as depression, epilepsy, and Alzheimer’s disease.

A team led by Sebastian Jessberger, Professor of Neurosciences at the Brain Research Institute, has now identified a novel mechanism that plays a key role in adult neurogenesis and is required for the life-long activity of neural stem cells. Prof. Jessberger believes that “this finding will hopefully give us a new target to develop novel drugs against depression or neurodegenerative diseases”. The results of this study were published on December 2^nd in the scientific journal Nature.

Stem cells produce their own lipids

Researchers in his group could show that stem cells depend on glucose-derived production of new fatty acids and lipids. When the key enzyme of this pathway, fatty acid synthase (Fasn), is blocked in neural stem cells, they loose their ability to divide which results in a reduction in newborn neurons.

To prevent the constant division of neural stem cells, this pathway is regulated by a protein called Spot14, which inhibits lipid synthesis. Controlling Fasn activity is important to make sure that stem cells do not divide too often, which could lead to a premature exhaustion or depletion of the stem cell pool. Surprisingly, the metabolic state of neural stem cells seems to be fundamentally distinct from their daughter cells (newborn neurons) and other dividing cells in the central nervous system. These other cell types are able to take up lipids from the blood stream and use them as important structural components of cell membranes but also for signaling events and as an energy source.

Potential target for new drugs

The study published by the Jessberger group has identified a novel target to pharmacologically enhance the activity of neural stem cells in diseases that are associated with reduced levels of newborn neurons, such as depression.

Marlen Knobloch, postdoc in the Jessberger lab and first author of the study, says: “Currently, we have to understand in much greater detail why neural stem cells are in this distinct metabolic state; to this end, we are currently performing experiments in the lab with the aim to enhance neurogenesis through manipulation of lipid metabolism”. However, one must not place too high expectations for the quick development of novel drugs, although for Simon Braun, co-first author of the study, “the hope certainly is to increase the number of newborn neurons by targeting lipid metabolism in the human brain”.

Study supports link between stress, epileptic seizures

Scientists have long thought that stress plays a role in epileptic seizures, and new evidence suggests that epilepsy patients who believe this is the case experience a different brain response when faced with a nerve-wracking situation.

Researchers from the University of Cincinnati performed functional MRI brain scans during a stressful math exercise on 16 epilepsy patients who pegged stress as a factor in their seizure control and seven patients who did not. While both groups performed similarly on the test, those who perceived stress to have an impact on their epilepsy showed greater brain activation than the others during intimidating parts of the test.

"One of the things we often hear is that a lot of epilepsy patients feel their seizures are affected by stress … but no one had really looked at their [brain response] or other elements of their physiological response," said study author Jane Allendorfer, an instructor of neurology at the University of Alabama at Birmingham. Allendorfer worked at University of Cincinnati while the study was conducted.

"We were a bit surprised to see this difference," she added, "but really excited to see it as well because this is something that hadn’t been done before."

The research was scheduled to be presented Monday at the annual meeting of the American Epilepsy Society, in San Diego. Data presented at scientific conferences often has not been peer-reviewed or published and is considered preliminary.

A brain disorder producing repeated seizures, epilepsy affects more than 2 million people in the United States, according to the U.S. Centers for Disease Control and Prevention. An estimated 50 million to 65 million people are affected by the condition worldwide.

New Research on How the Brain Makes Decisions

Neuroscience researchers at Trinity College Dublin have opened a new avenue for research on how the brain enables us to make decisions about our environment. By observing the gradual formation of a decision in brain activity before the particular decision was actually reported, the findings also have the potential to contribute to improved understanding and diagnosis of numerous brain disorders that are associated with impaired perceptual decision making. The discovery was recently published in Nature Neuroscience.

When interacting with our environment, we need to be sure about what we’re seeing, feeling or hearing in order to decide how to act. What does that road sign ahead say? Is that a train I hear approaching? Is it too dark for me to cycle home without a light? Somehow the brain enables us to make concrete decisions about the vast and often unreliable array of information it continually receives through the senses. One influential theory about how this might be achieved proposes that the brain allows information from the senses to accumulate over time and only commits to a particular decision once a reliable quantity has been gathered. While this theory has existed for several decades Assistant Professor, Redmond O’Connell at the Trinity College Institute of Neuroscience and colleagues are the first to have identified exactly how this occurs in the human brain.

The researchers designed a new test which required participants to detect a gradual change in a visual display or an auditory tone. The gradual change occurred over several seconds and was undetectable at first but eventually became obvious. This allowed the researchers to pinpoint the precise moment at which participants decided that a change had occurred. At the same time, the researchers recorded brain activity using electrodes placed on the scalp. Using this method the authors succeeded in isolating a brain signal that increased in parallel with the visual or auditory change and continued to increase thereafter. Most importantly, the authors found that participants only reported perceiving the change once this signal had reached a certain level. As a result, it was possible to precisely predict both the timing and accuracy of the participant’s decisions simply by monitoring this brain signal. In other words, it was possible to observe the gradual formation of a decision in the participant’s brain activity before that decision was actually reported.

Infants learn to look and look to learn

Researchers at the University of Iowa have documented an activity by infants that begins nearly from birth: They learn by taking inventory of the things they see.

In a new paper, the psychologists contend that infants create knowledge by looking at and learning about their surroundings. The activities should be viewed as intertwined, rather than considered separately, to fully appreciate how infants gain knowledge and how that knowledge is seared into memory.

“The link between looking and learning is much more intricate than what people have assumed,” says John Spencer, a psychology professor at the UI and a co-author on the paper published in the journal Cognitive Science.

The researchers created a mathematical model that mimics, in real time and through months of child development, how infants use looking to understand their environment. Such a model is important because it validates the importance of looking to learning and to forming memories. It also can be adapted by child development specialists to help special-needs children and infants born prematurely to combine looking and learning more effectively.

“The model can look, like infants, at a world that includes dynamic, stimulating events that influence where it looks. We contend (the model) provides a critical link to studying how social partners influence how infants distribute their looks, learn, and develop,” the authors write.