Neuroscience

Dyslexia, the most commonly diagnosed learning disability in the United States, is a neurological reading disability that occurs when the regions of the brain that process written language don’t function normally.

The use of non-invasive functional neuroimaging tools has helped characterize how brain activity is disrupted in dyslexia. However, most prior work has focused on only a small number of brain regions, leaving a gap in our understanding of how multiple brain regions communicate with one another through networks, called functional connectivity, in persons with dyslexia.

This led neuroscience PhD student Emily Finn and her colleagues at the Yale University School of Medicine to conduct a whole-brain functional connectivity analysis of dyslexia using functional magnetic resonance imaging (fMRI). They report their findings in the current issue of Biological Psychiatry.

"In this study, we compared fMRI scans from a large number of both children and young adults with dyslexia to scans of typical readers in the same age groups. Rather than activity in isolated brain regions, we looked at functional connectivity, or coordinated fluctuations between pairs of brain regions over time," explained Finn.

In total, they recruited and scanned 75 children and 104 adults. Finn and her colleagues then compared the whole-brain connectivity profiles of the dyslexic readers to the non-impaired readers, which revealed widespread differences.

Dyslexic readers showed decreased connectivity within the visual pathway as well as between visual and prefrontal regions, increased right-hemisphere connectivity, reduced connectivity in the visual word-form area, and persistent connectivity to anterior language regions around the inferior frontal gyrus. This altered connectivity profile is consistent with dyslexia-related reading difficulties.

Dr. John Krystal, Editor of Biological Psychiatry, said, “This study elegantly illustrates the value of functional imaging to map circuits underlying problems with cognition and perception, in this case, dyslexia.”

"As far as we know, this is one of the first studies of dyslexia to examine differences in functional connectivity across the whole brain, shedding light on the brain networks that crucially support the complex task of reading," added Finn. "Compared to typical readers, dyslexic readers had weaker connections between areas that process visual information and areas that control attention, suggesting that individuals with dyslexia are less able to focus on printed words."

Additionally, young-adult dyslexic readers maintained high connectivity to brain regions involved in phonology, suggesting that they continue to rely on effortful “sounding out” strategies into adulthood rather than transitioning to more automatic, visual-based strategies for word recognition.

A better understanding of brain organization in dyslexia could potentially lead to better interventions to help struggling readers.

McLean Hospital researchers are reporting that xenon gas, used in humans for anesthesia and diagnostic imaging, has the potential to be a treatment for post-traumatic stress disorder (PTSD) and other memory-related disorders.

“In our study, we found that xenon gas has the capability of reducing memories of traumatic events,” said Edward G. Meloni, PhD, assistant psychologist at McLean Hospital and an assistant professor of Psychiatry at Harvard Medical School. “It’s an exciting breakthrough, as this has the potential to be a new treatment for individuals suffering from PTSD.”

In the study, published in the current issue of PLOS ONE, Meloni, and Marc J. Kaufman, PhD, director of the McLean Hospital Translational Imaging Laboratory, examined whether a low concentration of xenon gas could interfere with a process called reconsolidation – a state in which reactivated memories become susceptible to modification. “We know from previous research that each time an emotional memory is recalled, the brain actually restores it as if it were a new memory. With this knowledge, we decided to see whether we could alter the process by introducing xenon gas immediately after a fear memory was reactivated,” explained Meloni.

The investigators used an animal model of PTSD called fear-conditioning to train rats to be afraid of environmental cues that were paired with brief footshocks. Reactivating the fearful memory was done by exposing the rats to those same cues and measuring their freezing response as a readout of fear. “We found that a single exposure to the gas, which is known to block NMDA receptors involved in memory formation in the brain, dramatically and persistently reduced fear responses for up to 2 weeks.  It was as though the animals no longer remembered to be afraid of those cues”, said Dr. Meloni.

Meloni points out that the inherent properties of a gas such as xenon make it especially attractive for targeting dynamic processes such as memory reconsolidation. “Unlike other drugs or medications that may also block NMDA receptors involved in memory, xenon gets in and out of the brain very quickly. This suggests that xenon could be given at the exact time the memory is reactivated, and for a limited amount of time, which may be key features for any potential therapy used in humans.”

“The fact that we were able to inhibit remembering of a traumatic memory with xenon is very promising because it is currently used in humans for other purposes, and thus it could be repurposed to treat PTSD,” added Kaufman.

For these investigators, several questions remain to be addressed with further testing. “From here we want to explore whether lower xenon doses or shorter exposure times would also block memory reconsolidation and the expression of fear. We’d also like to know if xenon is as effective at reducing traumatic memories from past events, so-called remote memories, versus the newly formed ones we tested in our study”.

Meloni and Kaufman indicate that future studies are planned to test if the effects of xenon in rats seen in their study translate to humans. Given that intrusive re-experiencing of traumatic memories – including flashbacks, nightmares, and distress and physiological reactions induced when confronted with trauma reminders – is a hallmark symptom for many who suffer from PTSD, a treatment that alleviates the impact of those painful memories could provide welcome relief.

Extremely low levels of the compound in marijuana known as delta-9-tetrahydrocannabinol, or THC, may slow or halt the progression of Alzheimer’s disease, a recent study from neuroscientists at the University of South Florida shows.

Findings from the experiments, using a cellular model of Alzheimer’s disease, were reported online in the Journal of Alzheimer’s Disease.

Researchers from the USF Health Byrd Alzheimer’s Institute showed that extremely low doses of THC reduce the production of amyloid beta, found in a soluble form in most aging brains, and prevent abnormal accumulation of this protein — a process considered one of the pathological hallmarks evident early in the memory-robbing disease. These low concentrations of THC also selectively enhanced mitochondrial function, which is needed to help supply energy, transmit signals, and maintain a healthy brain.

“THC is known to be a potent antioxidant with neuroprotective properties, but this is the first report that the compound directly affects Alzheimer’s pathology by decreasing amyloid beta levels, inhibiting its aggregation, and enhancing mitochondrial function,” said study lead author Chuanhai Cao, PhD and a neuroscientist at the Byrd Alzheimer’s Institute and the USF College of Pharmacy.

“Decreased levels of amyloid beta means less aggregation, which may protect against the progression of Alzheimer’s disease. Since THC is a natural and relatively safe amyloid inhibitor, THC or its analogs may help us develop an effective treatment in the future.”

The researchers point out that at the low doses studied, the therapeutic benefits of THC appear to prevail over the associated risks of THC toxicity and memory impairment.

Neel Nabar, a study co-author and MD/PhD candidate, recognized the rapidly changing political climate surrounding the debate over medical marijuana.

“While we are still far from a consensus, this study indicates that THC and THC-related compounds may be of therapeutic value in Alzheimer’s disease,” Nabar said. “Are we advocating that people use illicit drugs to prevent the disease? No. It’s important to keep in mind that just because a drug may be effective doesn’t mean it can be safely used by anyone. However, these findings may lead to the development of related compounds that are safe, legal, and useful in the treatment of Alzheimer’s disease.”

The body’s own system of cannabinoid receptors interacts with naturally-occurring cannabinoid molecules, and these molecules function similarly to the THC isolated from the cannabis (marijuana) plant.

Dr. Cao’s laboratory at the Byrd Alzheimer’s Institute is currently investigating the effects of a drug cocktail that includes THC, caffeine as well as other natural compounds in a cellular model of Alzheimer’s disease, and will advance to a genetically-engineered mouse model of Alzheimer’s shortly.

“The dose and target population are critically important for any drug, so careful monitoring and control of drug levels in the blood and system are very important for therapeutic use, especially for a compound such as THC,” Dr. Cao said.

Duke University researchers have found a ”roving detection system” on the surface of cells that may point to new ways of treating diseases like cancer, Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

The cells, which were studied in nematode worms, are able to break through normal tissue boundaries and burrow into other tissues and organs — a crucial step in many normal developmental processes, ranging from embryonic development and wound-healing to the formation of new blood vessels.

But sometimes the process goes awry. Such is the case with metastatic cancer, in which cancer cells spread unchecked from where they originated and form tumors in other parts of the body.

“Cell invasion is one of the most clinically relevant yet least understood aspects of cancer progression,” said David Sherwood, an associate professor of biology at Duke.

Sherwood is leading a team that is investigating the molecular mechanisms that control cell invasion in both normal development and cancer, using a one-millimeter worm known as C. elegans.

At one point in C. elegans development, a specialized cell called the anchor cell breaches the dense, sheet-like membrane that separate the worm’s uterus from its vulva, opening up the worm’s reproductive tract.

Anchor cells can’t see, so they need some kind of signal to tell them where to break through. In a 2009 study, Sherwood and colleagues discovered that an extracellular cue called netrin orients the anchor cell so that it invades in the right direction.

In a new study appearing Aug. 25 in the Journal of Cell Biology, the team shows how receptors on the invasive cells essentially rove around the cell membrane ”hunting” for the missing netrin signal that will guide the cell to the correct location.

The researchers used a video camera attached to a powerful microscope to take time-lapse movies of the slow movement of the C. elegans anchor cell during its invasion (Figure 1, Figure 2).

Their time-lapse analyses reveal that when netrin production is blocked, netrin receptors on the surface of the anchor cell periodically cluster, disperse and reassemble in a different region of the cell membrane. The receptors cluster alongside patches of actin filaments — thin flexible fibers that help cells change shape and form invasive protrusions –- that pop up in each new spot.

“It’s kind of like a missile detection system,” Sherwood said.

Rather than the whole cell having to move around, its receptors move around on the outside of the cell until they get a signal. Once the receptors locate the netrin signal, they stabilize in the region of the cell membrane that is closest to the source of the signal.

The findings redefine decades-old ideas about how the cell’s navigation system works. “Cells don’t just passively respond to the netrin signal — they’re actively searching for it,” Sherwood said.

Given that netrin has been found to promote cell invasion in some of the most lethal cancers, the findings could lead to new treatment strategies. Disrupting the cell’s netrin detection system, for example, could prevent cancer cells from finding their way to the bloodstream or the lymphatic system and stop them from metastasizing, or becoming invasive and spreading throughout the body.

“One of the things we’re gearing up to do next are drug screens with our collaborators to see if we can block this detection system during invasion,” Sherwood said.

Scientists have also known for years that netrin plays a key role in wiring the brain and nervous system by guiding developing nerve cells as they grow and form connections.

This means the results could also point to new ways of treating neurological disorders like Parkinson’s and ALS and recovering from spinal cord injuries.

Tinkering with the cell’s netrin detection machinery, for example, may make it possible to encourage damaged cells in the central nervous system — which normally have limited ability to regenerate — to regrow.

Researchers at the Gladstone Institutes and University of California, San Francisco have shown that a loss of cells in the retina is one of the earliest signs of frontotemporal dementia (FTD) in people with a genetic risk for the disorder—even before any changes appear in their behavior.

Published today in the Journal of Experimental Medicine, the researchers, led by Gladstone investigator Li Gan, PhD and UCSF associate professor of neurology Ari Green, MD, studied a group of individuals who had a certain genetic mutation that is known to result in FTD. They discovered that before any cognitive signs of dementia were present, these individuals showed a significant thinning of the retina compared with people who did not have the gene mutation.

“This finding suggests that the retina acts as a type of ‘window to the brain,’” said Dr. Gan. “Retinal degeneration was detectable in mutation carriers prior to the onset of cognitive symptoms, establishing retinal thinning as one of the earliest observable signs of familial FTD. This means that retinal thinning could be an easily measured outcome for clinical trials.”

Although it is located in the eye, the retina is made up of neurons with direct connections to the brain. This means that studying the retina is one of the easiest and most accessible ways to examine and track changes in neurons.

Lead author Michael Ward, MD, PhD, a postdoctoral fellow at the Gladstone Institutes and assistant professor of neurology at UCSF, explained, “The retina may be used as a model to study the development of FTD in neurons. If we follow these patients over time, we may be able to correlate a decline in retinal thickness with disease progression. In addition, we may be able to track the effectiveness of a treatment through a simple eye examination.”

The researchers also discovered new mechanisms by which cell death occurs in FTD. As with most complex neurological disorders, there are several changes in the brain that contribute to the development of FTD. In the inherited form researched in the current study, this includes a deficiency of the protein progranulin, which is tied to the mislocalization of another crucial protein, TDP-43, from the nucleus of the cell out to the cytoplasm.

However, the relationship between neurodegeneration, progranulin, and TDP-43 was previously unclear. In follow-up studies using a genetic mouse model of FTD, the scientists were able to investigate this connection for the first time in neurons from the retina. They identified a depletion of TDP-43 from the cell nuclei before any signs of neurodegeneration occurred, signifying that this loss may be a direct cause of the cell death associated with FTD.

TDP-43 levels were shown to be regulated by a third cellular protein called Ran. By increasing expression of Ran, the researchers were able to elevate TDP-43 levels in the nucleus of progranulin-deficient neurons and prevent their death.

“With these findings,” said Dr. Gan, “we now not only know that retinal thinning can act as a pre-symptomatic marker of dementia, but we’ve also gained an understanding into the underlying mechanisms of frontotemporal dementia that could potentially lead to novel therapeutic targets.”

University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer’s and other diseases.

The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow many cell types, including cells called astrocytes and microglia, to be studied in a new way.

"This is opening up the possibility to decipher how the brain works," said Petr Tvrdik, Ph.D., a research fellow in human genetics and a senior author on the study.

The research was published Aug. 14, 2014, in Neuron, a world-leading neuroscience journal. The work is the result of a three-year study involving multiple labs connected with The Brain Institute at the University of Utah. The lead author is J. Michael Gee, who is pursuing both a medical degree and a graduate degree in bioengineering at the university.

"We’re really in the era of team science," said John White, Ph.D., professor of bioengineering, executive director of the Brain Institute and the study’s corresponding author.

With the new mouse line, scientists can use a laser-based fluorescence microscope to study the calcium indicator in the glial cells of the living mouse, either when the mouse is anesthetized or awake. Calcium is studied because it is an important signaling molecule in the body and it can reveal how well the brain is functioning.

Using this method, the scientists are essentially creating a window into the working brain to study the interactions between neurons, astrocytes and microglia.

"We believe this will give us new insights for treatments of epilepsy and for new views of how the immune system of the brain works," White said.

About one-third of the 3 million Americans estimated to have epilepsy lack adequate treatment to manage the disease.

Describing a long-standing collaboration with fellow university researcher and professor of pharmacology and toxicology Karen Wilcox, Ph.D., White said, “We believe the glial cells are malfunctioning in epilepsy. What we’re trying to do is find out in what ways astrocytes participate in the disease.”

This research is expected to lead to new classes of drugs.

The ability to track calcium changes in microglial cells will also open up the possibility of studying inflammatory diseases of the brain. Every neurological disease, including Multiple Sclerosis and Alzheimer’s, appears to include components of inflammation, the scientists said.

"Live imaging and monitoring microglial activity and responses to inflammation was not possible before," said Tvrdik, particularly in living animals. In the past, researchers studied post-mortem tissue or relied on invasive approaches using synthetic dyes.

A new study of self-awareness by Kessler Foundation researchers shows that persons with multiple sclerosis (MS) may be able to improve their self-awareness through task-oriented cognitive rehabilitation. The study was epublished ahead of print on July 2 in NeuroRehabilitation. Self-awareness is one’s ability to recognize cognitive problems caused by brain injury. This is the first study of self-awareness in MS that includes assessment of online awareness, as well as metacognitive awareness. 

Yael Goverover, PhD, OT, is a visiting scientist at Kessler Foundation. She is an associate professor at New York University. Dr. Goverover is a recipient of the National Institute on Disability and Rehabilitation Research Fellowship award (Mary Switzer Award). Drs. Genova, Chiaravalloti and DeLuca are MS researchers at Kessler Foundation.

The researchers assessed 18 people with MS and 16 healthy controls for 2 types of self-awareness - metacognitive knowledge of disabilities (or intellectual awareness) and online awareness (emergent or anticipatory awareness). They also looked at the relationships among self-awareness, functional performance and quality of life (QoL). Assessment involved the Functional Behavior Profile, questionnaires administered before and after functional tasks (purchasing cookies and airline tickets via the Internet) and the Functional Assessment of Multiple Sclerosis measure. 

“Results showed that compared with controls, people with MS assessed their actual performance more realistically following completion of a task. This suggests that individuals may be able to improve their self-awareness through more experience with tasks,” noted Nancy Chiaravalloti, PhD, director of Neuropsychology & Neuroscience Research at Kessler Foundation.

"Research that leads to better understanding of types of self-awareness, functional outcomes and QOL will aid the development of effective assessments and rehabilitation interventions,” said Dr. Chiaravalloti. “The association between online awareness and task performance in this study, for example, may have implications for cognitive rehabilitation strategies in the MS population.”

In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and challenges facing the scientific community as therapies involving stem cells move closer to reality. 

The review article focuses on pluripotent stem cells (PSCs), which are stem cells that can give rise to all cell types. These include both embryonic stem cells, and those derived from mature cells that have been “reprogrammed” or “induced” – a process typically involving a patient’s own skin cells – so that they possess the characteristics of stem cells found at the earliest stage of development. These cells can then be differentiated, through careful manipulation of chemical and genetic signaling, to become virtually any cell type found in the body. 

While the process of making induced PSCs is relatively new in scientific terms – it was first demonstrated that skin cells could be successfully reprogrammed in 2007 – one of the reasons that these cells are viewed with promise by the scientific community is because they are derived from the patient’s own tissue. Consequently, cells used for transplant can be a genetic match and far less likely to be rejected, thereby potentially mitigating the need to use immune system suppressing drugs. 

The article addresses the current state of efforts to apply PSCs to treat a number of diseases, including diabetes, liver disease, and heart disease. Goldman, a distinguished professor and co-director of the University of Rochester School of Medicine and Dentistry Center for Translational Neuromedicine, reviewed the current state of therapies for neurological diseases. 

While progress has been made over the last several years, the authors point out that significant challenges remain. Scientists must be able to obtain the precise cell populations required to treat the target disease, and once transplanted, make sure that these cells get to where they are needed and integrate into existing tissue. The cells that are transplanted must also first be checked for purity and screened for unwanted cells that could give rise to tumors. 

Goldman and his co-authors contend that “the brain is arguable the most difficult of the organs in which to employ stem cell-based therapeutics.” The complex connections and interdependency between neurons and the myriad of other support cells found in central nervous mean that a precise reconstruction of damaged areas of the brain is often impractical. Also, many degenerative neurological disorders, including Alzheimer’s, involve more than one cell type, making them difficult targets for stem cell therapies, at least in the near future.

Instead, Goldman argues that neurological diseases that involve a single cell type – at least at the early stages – are more promising targets for PSC-based therapies. These include Parkinson’s disease and Huntington’s disease, which are characterized by the loss of dopamine-producing neurons and medium spiny neurons, respectively. In particular, diseases that involved support cells found in the brain known as glia – such as multiple sclerosis, white matter stroke, cerebral palsy, and pediatric leukodystrophies – are especially strong candidates for stem cell therapies. These diseases are characterized by the loss of a specific glial cell type called the oligodendrocyte, which makes myelin, the insulation that allows electrical signals to travel between nerve cells. In multiple sclerosis, the body’s own immune system attacks and destroys these cells and, over time, communication between cells is disrupted or even lost.

Oligodendrocytes are the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Scientists have long speculated that, if successfully transplanted into the diseased or injured brain, OPCs might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases. 

Goldman’s group has already shown that OPCs produced from PSCs obtained from human skin cells successfully restore myelin in the brains and spinal cords of myelin-deficient mice, and can rescue and restore function to mice that would have otherwise died. While this work demonstrated the promise of stem cell therapies, it also illustrated the challenges facing scientists. It took Goldman’s lab four years to establish the exact chemical signaling required to reprogram, produce, and ultimately purify OPCs in sufficient quantities for transplantation, and only recently has the group developed methods for producing the cells in purity and quantity sufficient to transplant into humans.

The authors contend that future progress will depend upon continued close collaboration between scientists and clinicians, and between academia, industry and regulatory bodies to overcome the remaining barriers to bringing new stem cell-based therapies to patients with these devastating diseases.

In an environment where others struggle to survive, Tibetans thrive in the thin air on the Tibetan Plateau, with an average elevation of 14,800 feet. A University of Utah led discovery that hinged as much on strides in cultural diplomacy as on scientific advancements, is the first to identify a genetic variation, or mutation, that contributes to the adaptation, and to reveal how it works. The research appears online in the journal Nature Genetics on Aug. 17, 2014.

“These findings help us understand the unique aspects of Tibetan adaptation to high altitudes, and to better understand human evolution,” said Josef Prchal, M.D., senior author and University of Utah professor of internal medicine.

For his research, Prchal needed Tibetans to donate blood, from which he could extract their DNA, a task that turned out to be more difficult than he ever imagined. It took several trips to Asia, meeting with Chinese officials and representatives of exiled Tibetans in India, to get the necessary permissions to recruit subjects for the study. But he quickly learned that official documents would not be enough. Wary of foreigners, the Tibetans refused to participate.

To earn the Tibetans’ trust, Prchal obtained a letter of support from the Tibetan spiritual leader, the Dalai Lama. “The Dalai Lama felt that a better understanding of the adaptation would be helpful not only to the Tibetan community but also to humanity at large,” said Prchal. He also enlisted the help of native Tibetan Tsewang Tashi, M.D., an author and clinical fellow at the Huntsman Cancer Institute at the University of Utah. More than 90 Tibetans, both from the U.S. and abroad, volunteered for the study.

Published in Science in 2010, Prchal’s group was the first to establish that there was a genetic basis to Tibetan high altitude adaptation. In the intervening years, first author Felipe Lorenzo, M.D., Ph.D., pioneered new techniques to tease out the secret to one of the adaptations from a “GC-rich” region of the Tibetans’ DNA that was particularly difficult to penetrate.

Their efforts were worth it; the DNA had a fascinating story to tell. About 8,000 years ago, the gene EGLN1 changed by a single DNA base pair. Today, a relatively short time later on the scale of human history, the vast majority of Tibetans – 88 percent - have the genetic variation, and it is virtually absent from closely related lowland Asians. The findings indicate the tiny genetic change endows its carriers with a selective advantage.

Prchal collaborated with experts throughout the world, including co-senior author Peppi Koivunen, Ph.D., from Biocenter Oulu in Finland, to determine that the newly identified genetic variation protects Tibetans by decreasing an aversive over-response to low oxygen. In those without the adaptation, the thin air causes their blood to become thick with oxygen-carrying red blood cells, often causing long-term complications such as heart failure. The EGLN1 variation, together with other unidentified genetic changes, collectively support life at high altitudes.

Prchal says the research also has broader implications. Because oxygen plays a central role in human physiology and disease, a deep understanding of how high altitude adaptations work may lead to novel treatments for various conditions, including cancer. “There is much more that needs to be done, and this is just the beginning,” he said.

When traveling with Tashi in Asia, Prchal was surprised at how he was able to get Tibetans to grasp the research they were being asked to take part in. Tashi simply helped them realize that their ability to adapt to life at high altitude was unique. “They usually responded by a little initial surprise quickly followed by agreement,” said Tashi. “It was as if I made them realize something new, which only then became obvious.”

Listen to an interview with Josef Prchal, Tsewang Tashi, and Felipe Lorenzo on The Scope Radio.

As brain surgeons test new procedures and drugs to treat conditions ranging from psychiatric disorders to brain cancer, accuracy is becoming an ever-greater issue.

In treating the brain, the state of the art today starts with images from a magnetic resonance (MR) scanner, usually made a few days before surgery. Then, in the operating room, multiple cameras track instruments as they are inserted through a hole in the skull, creating images that can be superimposed on the original MR scans.

But there is no guarantee that the brain will not shift slightly during the surgery and throw off the best efforts at exact guidance.

For 20 years, neurosurgeons have discussed a radical way to achieve real-time accuracy in placement: performing surgery with the brain inside an MR machine, says Walter Block, professor of biomedical engineering at the University of Wisconsin-Madison. “When you open the brain for surgery, the tissue can shift slightly, and that will throw off predictions made in advance.”

To bring the full promise of MR into the operating room, Block has formed a company called InseRT MRI to develop software that allows surgeons to observe the brain in real time on an MR machine during surgery.

Such a system would have a number of applications, he says. Drugs for brain cancer can be delivered over as long as 54 hours. “It would be valuable to see where the drug is going during the first few hours,” Block says. “Drugs move at different rates through gray and white matter, and this ability to recalibrate the treatment plan, based on actual data on where the drug is moving, would allow you to alter the location of the catheter or the flow rate of the medication.”

To get that accuracy advantage, Block does not envision forcing surgeons to learn a new operating environment. “Surgeons have operating room tools and work stations that are familiar to them,” he says. “We are creating a set of tools that make the MR space a comfortable place for the surgeon.”

UW-Madison neurosurgeon Azam Ahmed plans to use the system through test procedures on animal brains and cadavers, Block says. “We are working with Dr. Ahmed to design the workflow so it’s intuitive to him. We are not going to piggyback on top of a large scanner market designed for largely diagnostic purposes, kludging it to make it work for interventional applications.”

The goal is not to develop software that could be spliced into MR manufacturers’ systems, he says, “since every time they alter their software, we would have to change ours.” Instead, Block is borrowing tactics from the smartphone industry. “People write apps that use various phone resources — GPS, the screen, the orientation system. We look at the MR scanner as a set of resources that we can control. An app writer does not have to go to Samsung or Apple and say, ‘We have this idea.’”

Block says his software will interact with the MR machine through a software “portal” being developed by another firm.

One obvious market is the pharmaceutical industry. “Any drug trial in the brain will cost hundreds of millions of dollars,” he says, “and we often see trials being repeated after post-mortem analysis raises questions about the accuracy of drug placement.”

Targeted surgery could also help remove bits of brain tissue to treat severe epilepsy. Marvel Medtech in Cross Plains, Wisconsin, is developing a system that would employ InseRT MRI’s guidance to biopsy breast tumors. The technology also raises the potential for localized psychiatric drug therapy, Block says.

In the brain, the MR-guidance system is already accurate to less than a millimeter, Block says. While conventional stereotactic systems can approach that accuracy “in the best case,” the error can rise to 1.5 or 2 millimeters — a vast distance in an organ as delicate as the human brain, in which damage to healthy tissue must be minimized.

Block says InseRT MRI’s competitive advantage resides in his long experience in medical imaging. “Our value is (faster) time to market. We have come up with ways to circumvent the significant hurdles that now limit image-guided therapy, and we believe we can do this faster than anybody else.”

According to researchers at the University of Montreal, the regions of the brain below the cortex play an important role as we train our bodies’ movements and, critically, they interact more effectively after a night of sleep. While researchers knew that sleep helped us the learn sequences of movements (motor learning), it was not known why. “The subcortical regions are important in information consolidation, especially information linked to a motor memory trace. When consolidation level is measured after a period of sleep, the brain network of these areas functions with greater synchrony, that is, we observe that communication between the various regions of this network is better optimized. The opposite is true when there has been no period of sleep,” said Karen Debas, neuropsychologist at the University of Montreal and leader author of the study. A network refers to multiple brain areas that are activated simultaneously.

To achieve these results, the researchers, led by Dr. Julien Doyon, Scientific Director of the Functional Neuroimaging Unit of the Institut universitaire de gériatrie de Montréal Research Centre, taught a group of subjects a new sequence of piano-type finger movements on a box. The brains of the subjects were observed using functional magnetic resonance imaging during their performance of the task before and after a period of sleep. Meanwhile, the same test was performed by a control group at the beginning and end of the day, without a period of sleep.

The researchers had already shown that the putamen, a central part of the brain, was more active in subjects who had slept. Furthermore, they had observed improved performance of the task after a night of sleep and not the simple passage of daytime. Using a brain connectivity analysis technique, which identifies brain networks and measures their integration levels, they found that one network emerged from the others—the cortico-striatal network—composed of cortical and subcortical areas, including the putaman and associated cortical regions. “After a night of sleep, we found that this network was more integrated than the others, that is, interaction among these regions was greater when consolidation had occurred. A night of sleep seems to provide active protection of this network, which the passage of daytime does not provide. Moreover, only a night of sleep results in better performance of the task,” Debas said.

These results provide insight into the role of sleep in learning motor skills requiring new movement sequences and reveal, for the first time, greater interaction within the cortico-striatal system after a consolidation phase following sleep. “Our findings open the door to other research opportunities, which could lead us to better understand the mechanisms that take place during sleep and ensure better interaction between key regions of the brain. Indeed, several other studies in my laboratory are examining the role of sleep spindles—brief physiological events during non-rapid eye movement sleep—in the process of motor memory trace consolidation,” Doyon said. “Ultimately, we believe that we will better be able to explain and act on memory difficulties presented by certain clinical populations who have sleeping problems and help patients who are relearning motor sequences in rehabilitation centres,” Debas said.

Individuals with schizophrenia often have trouble engaging in daily tasks or setting goals for themselves, and a new study from San Francisco State University suggests the reason might be their difficulty in assessing the amount of effort required to complete tasks.

The research, detailed in an article published this week in the Journal of Abnormal Psychology, can assist health professionals in countering motivation deficits among patients with schizophrenia and help those patients function normally by breaking up larger, complex tasks into smaller, easier-to-grasp ones.

"This is one of the first studies to carefully and systematically look at the daily activities of people with schizophrenia — what those people are doing, what goals are they setting for themselves," said David Gard, an associate professor of psychology at SF State who has spent years researching motivation and emotion. "We knew that people with schizophrenia were not engaging in a lot of goal-directed behavior. We just didn’t know why."

In 2011, Gard received a grant from the National Institute of Mental Health to study the reasons behind this difficulty in goal setting. An earlier article detailing other research from this study, published in May in the journal Schizophrenia Research, showed that when people with schizophrenia do set goals for themselves, they set them for the same reasons as persons without: to connect with others. But motivation deficits are still common among these individuals, and his latest study set out to pinpoint the reason.

Through a series of cognitive assessments and random phone calls, Gard and his colleagues at SF State and the University of California, San Francisco collected data from 47 people with and 41 people without schizophrenia. Participants were called four times a day, randomly throughout the day, for a week and asked about their current mood, as well as what they were doing; how much enjoyment they were getting out of it; and what their goals for the rest of the day were. The results were coded by variables such as how much pleasure they were getting out of their daily activities and how much effort was involved, then compared that with the results from the cognitive assessments.

Gard and his fellow researchers found that, while people with schizophrenia engage in low-impact, pleasurable goals — such as watching TV or eating food for enjoyment — as much as others, they have greater difficulty with more complex undertakings or goals requiring more effort.

"There’s something breaking down in the process around assessing high-effort, high-reward goals," Gard said. "When the reward is high and the effort is high, that’s when people with schizophrenia struggle to hold in mind and go after the thing that they want for themselves."

The findings indicate that health-care providers who want to help individuals with schizophrenia set goals for themselves should break larger tasks into smaller, simpler ones with small rewards. For example, instead of guiding a patient specifically toward the larger goal of getting in physical shape, a provider could instead encourage them to gradually walk a little bit more every day.

"That’s something we would do for everyone else, but it might have been avoided in patients with schizophrenia because we thought they weren’t experiencing as much pleasure from their activities as they actually are," Gard added. "We can help them to identify things that are pleasurable and reward them toward larger goals."