Keeping you up to date on recent headlines in neurology

Our brains wired so we can better hear ourselves . . . Like the mute button on the TV remote control, our brains filter out unwanted noise so we can focus on what we're listening to. But when it comes to following our own speech, a new brain study from the University of California, Berkeley, shows that instead of one homogenous mute button, we have a network of volume settings that can selectively silence and amplify the sounds we make and hear. Neuroscientists from UC Berkeley, UCSF and Johns Hopkins University (Baltimore) tracked the electrical signals emitted from the brains of hospitalized epilepsy patients. They discovered that neurons in one part of the patients' hearing mechanism were dimmed when they talked, while neurons in other parts lit up. Their findings, published in the Journal of Neuroscience, offer new clues about how we hear ourselves above the noise of our surroundings and monitor what we say. Previous studies have shown a selective auditory system in monkeys that can amplify their self-produced mating, food and danger alert calls, but until this latest study, it was not clear how the human auditory system is wired. “We used to think that the human auditory system is mostly suppressed during speech, but we found closely knit patches of cortex with very different sensitivities to our own speech that paint a more complicated picture,“ said Adeen Flinker, a doctoral student in neuroscience at UC Berkeley and lead author of the study. “We found evidence of millions of neurons firing together every time you hear a sound right next to millions of neurons ignoring external sounds but firing together every time you speak,“ Flinker added. “Such a mosaic of responses could play an important role in how we are able to distinguish our own speech from that of others.“ While the study doesn't specifically address why humans need to track their own speech so closely, Flinker theorizes that, among other things, tracking our own speech is important for language development, monitoring what we say and adjusting to various noise environments. “Whether it's learning a new language or talking to friends in a noisy bar, we need to hear what we say and change our speech dynamically according to our needs and environment,“ Flinker said. He noted that people with schizophrenia have trouble distinguishing their own internal voices from the voices of others, suggesting that they may lack this selective auditory mechanism. The findings may be helpful in better understanding some aspects of auditory hallucinations, he said.

Key protein discovered that allows nerve cells to repair . . . A team of scientists led by Melissa Rolls, an assistant professor of biochemistry and molecular biology at Penn State University (St. College, Pennsylvania), has peered inside neurons to discover an unexpected process that is required for regeneration after severe neuron injury. The process was discovered during Rolls's studies aimed at deciphering the inner workings of dendrites – the part of the neuron that receives information from other cells and from the outside world. The research will be published in the Dec. 21 print edition of the scientific journal Current Biology. “We already know a lot about axons – the part of the nerve cell that is responsible for sending signals,“ Rolls said. “However, dendrites – the receiving end of nerve cells – have always been quite mysterious.“ Unlike axons, which form large, easily recognizable bundles, dendrites are highly branched and often buried deep in the nervous system, so they have always been harder to visualize and to study. However, Rolls and her team were able to get around these difficulties. They looked inside dendrites in vivo by using a simple model organism – the fruit fly – whose nerve cells are similar to human nerve cells. One of the first mysteries they tackled was the layout of what Rolls referred to as intracellular “highways“ – or microtubules. Unlike many other cells in our bodies, most neurons must last a lifetime. They rely on their key infrastructure — microtubules — to be extremely well organized, but also to be flexible so that they can be rebuilt in response to injury. Part of that flexibility comes microtubules' ability to grow constantly. Rolls and her team visualized this growth and realized that there must be a set of proteins controlling just how the highways are laid down at key intersections — or branch points — to keep all the microtubules pointing the same way. They identified the proteins, which include the motor protein kinesin-2, and found that when these proteins were missing the microtubules no longer pointed the same way in dendrites; that is, their polarity became disorganized. After identifying the set of proteins required to maintain an orderly microtubule infrastructure in dendrites, the team tested whether these proteins play a role in the ability of neurons to respond to injury. Most neurons are irreplaceable, and yet they have an incredible ability to regenerate their missing parts. In earlier studies, Rolls and her team had found that, after an axon is cut off and the nerve cell no longer is able to send signals, a new axon grows from the other side of the cell; that is, from a dendrite. As part of this process, the microtubules must flip polarity. In other words, the dendrite highways must be completely rebuilt in the axonal direction. “When we disabled the flies' ability to produce the kinesin-2 protein, we found that the highways could not be rebuilt correctly, and nerve regeneration failed,“ Rolls explained. “Apparently, kinesin-2 is a crucial protein for polarity maintenance and for the ability to set up a new highway system when neurons need to regenerate.“

Cerebrospinal fluid study reveals potential new AD gene . . . A genomic study of cerebrospinal fluid (CSF) has added a new gene to the list of potential genetic contributors to Alzheimer's disease, a national research team led by Indiana University School of Medicine (Bloomington, Indiana) scientists has reported. The research team conducted a genome-wide analysis of potential CSF biomarkers that could be used for early detection of Alzheimer's disease, using samples from 374 participants in the national Alzheimer's Disease Neuroimaging Initiative (ADNI). “This study was one of the first genome-wide analyses of biomarkers in cerebrospinal fluid, which has direct access to the brain and allows you to look at biochemical features that might be more directly tied to the disease,“ said Andrew Saykin, PsyD, Raymond C. Beeler Professor of Radiology and Imaging Sciences and director of the IU Center for Neuroimaging. The study was reported in the online edition of Neurology. In the genome-wide association study, researchers looked for genetic variations that could be related to CSF levels of three proteins – beta amyloid, tau and phosphorylated tau – that are linked to damage seen in brains of Alzheimer's patients. The primary novel finding was that a gene known as enhancer of polycomb homolog 2 (EPC2) was associated with total levels of the tau protein in the cerebrospinal fluid. This gene, which has not previously surfaced in other studies looking for Alzheimer-related markers, has been associated with a gene deletion syndrome that includes mental retardation, short stature and epilepsy. EPC2 is also involved in the formation of a DNA structure, heterochromatin, that plays a role in the activation and control of gene activity. That process, called epigenetics, refers to the alteration of gene expression by factors beyond the instructions in the DNA itself, including environmental factors. “The association of CSF tau and the EPC2 gene suggests a possible epigenetic mechanism that warrants follow-up in other samples. These epigenetic processes, in which genome function can be modified through interacting with the internal or external environment, are suspected of playing a role in neurodegenerative diseases such as Alzheimer's,“ said Saykin, who leads the Alzheimer's Disease Neuroimaging Initiative genetics component.

Fighter pilots' brains are wired differently . . . Fighter pilots' brains are “wired“ differently suggests new research from the UK that used cognitive tests and MRI scans to show there are significant differences in the white matter connections between brain regions of fighter pilots compared to a group of healthy volunteers with no flying experience. The researchers said they don't know if the pilots were born with differently wired brains or if their brain wiring changed as they learned their expertise. The study was the work of senior author Masud Husain, PhD, a professor at the Institutes of Neurology and Cognitive Neuroscience at University College London (UCL), and colleagues from UCL and the University of Cambridge. The study was published in the Dec. 15 issue of the Journal of Neuroscience. For the study, Husain and colleagues compared the cognitive performance of 11 fighter pilots to a group of healthy controls with similar IQ but no experience of flying aircraft. They also took MRI scans of their brains. Husain told the press they were interested in pilots because they often have to perform at the limits of human cognitive capability, “they are an expert group making precision choices at high speed,“ often in the presence of conflicting clues. The front-line Royal Air Force (RAF) Tornado fighter pilots and the controls completed two cognitive exercises: the “Eriksen Flanker“ and “change of plan tasks“ to assess the effect of distracting information on speed and accuracy of decisions, and ability to update a response plan in the presence of conflicting visual cues. In the Flanker test they had to press a right or left arrow key depending on the direction of an arrow on a screen in front of them. The arrow was surrounded by other distracting arrows pointing in different directions. In the change of plan test they had to respond quickly to a “go“ signal, unless instructed to change their plan before making a response. On the Flanker test, the pilots performed at the same speed but with greater accuracy than their age-matched controls. The pilots demonstrated superior cognitive control, “indexed by accuracy and post conflict adaptation,“ and also showed “increased sensitivity to irrelevant, distracting choices,“ wrote the authors. On the second test, the pilots' ability to “inhibit a current action plan in favor of an alternative response“ was no better than that of the controls. These results led the researchers to suggest that expertise in cognitive control may be more attuned to specific tasks and not generally better overall.

– Compiled by Rob Kimball, MDD