The Developing Brain: There is no final, optimal state

To reflect the ongoing structural changes in the adolescent and twenty-something brain, many journalists and scientists use words and phrases like “unfinished,” “work in progress,” “under construction” and “half-baked.”

Such language implies that the brain eventually reaches a kind of ideal state when it is “done.” But there is no final, optimal state.

The human brain is not a soufflé that gradually expands over time and finally finishes baking at age 30.

Yes, we can identify and label periods of dramatic development—or windows of heightened plasticity—but that should not eclipse the fact that brain changes throughout life.

Whether we can, at this moment in time, meaningfully link this life stage to neuroscience seems a tenuous proposition at best. By itself, brain biology does not dictate who we are.

The members of any one age group are not reducible to a few distinguishing structural changes in the brain.

Ultimately, the fact that a twenty-something has weaker bridges between various brain regions than someone in their thirties is not hugely important—it’s just one aspect of a far more complex identity.

DLR Robot: Paralysed woman uses thoughts to control robot

Almost 15 years after being paralysed by a stroke, a 58-year-old US-American woman was once again able to serve herself a drink of coffee.

This was possible thanks to a state-of-the-art DLR robot arm and hand that she controlled with neural signals sent directly from her brain.

It took just a few moments for her to grasp the drinking bottle with the robot hand, bring it up to her mouth and drink the coffee through a straw.

To accomplish this, software decoded neural signals recorded from a small array of electrodes that reflected her intention to reach and grasp, and converted them into commands that directed the robot arm and hand.

Researchers at the German Aerospace Center (Deutsches Zentrum für Luft- und Raumfahrt; DLR) present the results of their collaboration with Brown University, the United States Department of Veterans Affairs, and Massachusetts General Hospital in the 17 May 2012 issue of the scientific journal Nature.

Leukoaraiosis: 'Harmless' condition shown to alter brain function in elderly

Researchers at the Mayo Clinic say a common condition called leukoaraiosis, made up of tiny areas in the brain that have been deprived of oxygen.

They appear as bright white dots on MRI scans, is not a harmless part of the aging process, but rather a disease that alters brain function in the elderly.

Results of their study are published online in the journal Radiology. "There has been a lot of controversy over these commonly identified abnormalities on MRI scans and their clinical impact," said Kirk M. Welker, M.D., assistant professor of radiology in the College of Medicine at Mayo Clinic in Rochester, Minn.

"In the past, leukoaraiosis has been considered a benign part of the aging process, like gray hair and wrinkles."

 Leukoaraiosis, also called small vessel ischemia and often referred to as unidentified bright objects or "UBOs" on brain scans, is a condition in which diseased blood vessels lead to small areas of damage in the white matter of the brain.

The lesions are common in the brains of people over the age of 60, although the amount of disease varies among individuals.

"We know that aging is a risk factor for leukoaraiosis, and we suspect that high blood pressure may also play a role," Dr. Welker said.

Dr. Welker's team performed functional MRI (fMRI) scans on cognitively normal elderly participants recruited from the Mayo Clinic Study of Aging between 2006 and 2010.

In 18 participants, the amount of leukoaraiosis was a moderate 25 milliliters, and in 18 age-matched control participants, the amount of disease was less than five milliliters.

The patients were imaged in an MRI scanner as they performed a semantic decision task by identifying word pairs and a visual perception task that involved differentiating straight from diagonal lines.

fMRI is a special type of magnetic resonance imaging that measures metabolic changes in an active part of the brain.

Although both groups performed the tasks with similar success, the fMRI scans revealed different brain activation patterns between the two groups.

Compared to members of the control group, patients with moderate levels of leukoaraiosis had atypical activation patterns, including decreased activation in areas of the brain involved in language processing during the semantic decision task and increased activation in the visual-spatial areas of the brain during the visual perception task.

"Different systems of the brain respond differently to disease," Dr. Welker explained. "White matter damage affects connections within the brain's language network, which leads to an overall reduction in network activity."

He pointed out that identifying leukoaraiosis in the brain is important, both for individual patients undergoing brain mapping for surgery or other treatments and for research studies.

 For improved neurological health, Dr. Welker said efforts should be taken to prevent leukoaraiosis from occurring.

"Our results add to a growing body of evidence that this is a disease we need to pay attention to," he said.

"Leukoaraiosis is not a benign manifestation of aging but an important pathologic condition that alters brain function."

Anti-anxiety Drug calms fears by altering brain chemistry

An advance in understanding the brain’s fear circuitry has been revealed by a research team. They say it may hold particular promise for people at risk for anxiety disorders, including those suffering post-traumatic stress disorder (PTSD). Findings are reported in the journal Molecular Psychiatry.

“What is most compelling is our ability to translate first from mice to human neurobiology and then all the way out to human behaviour,” says Ahmad Hariri, a neurobiologist at Duke University. “That kind of translation is going to define the future of psychiatry and neuroscience.”

Read the original study DOI: 10.1038/mp.2012.72

 

The common thread in their studies is a gene encoding an enzyme called fatty acid amide hydrolase, or FAAH.

The enzyme breaks down a natural endo-cannabinoid chemical in the brain that acts in essentially the same way that Cannabis, aka marijuana, does (hence the name endo-cannabinoid).

Earlier studies had suggested that blocking the FAAH enzyme could decrease fear and anxiety by increasing endo-cannabinoids, which is consistent with the decreased anxiety some experience after smoking marijuana.

In 2009, Hariri’s lab found that a common variant in the human FAAH gene leads to decreased enzyme function with affects on the brain’s circuitry for processing fear and anxiety.

In the new study, Andrew Holmes’ group at the National Institute on Alcoholism and Alcohol Abuse tested the effects of a drug that blocks FAAH activity in fear-prone mice that had also been trained to be fearful through experiences in which they were delivered foot shocks.

Tests for the ability of those mice to get over their bad experiences found that the drug allowed a faster recovery from fear thanks to higher brain endo-cannabinoid levels.

More specifically, the researchers showed that those drug effects traced to the amygdala, a small area of the brain that serves as a critical hub for fear processing and learning.

To test for the human relevance of the findings, Hariri’s group went back to the genetic variant they had studied earlier in a group of middle-aged adults.

They showed study participants a series of pictures depicting threatening faces while they monitored the activity of their amygdalas using functional magnetic resonance imaging (fMRI) scans. They then looked for how the genetic variant affected this activity.

While the activity of the amygdala in all participants decreased over repeated exposures to the pictures. But people who carried the version of the FAAH gene associated with lower enzyme function and higher endo-cannabinoid levels showed a greater decrease in activity.

Hariri says that suggests that those individuals may be better able to control and regulate their fear response.

Further confirmation came from an analysis led by Duke’s Avshalom Caspi and Terrie Moffitt of 1,000 individuals in the Dunedin Study, who have been under careful observation since their birth in the 1970s in New Zealand.

Consistent with the mouse and brain imaging studies, those New Zealanders carrying the lower-expressing version of the FAAH gene were found to be more likely to keep their cool under stress.

“This study in mice reveals how a drug that boosts one of the brain’s naturally occurring endo-cannaboids enables fear extinction, a process that forms the basis of exposure therapy for PTSD,” Holmes says.

“It also shows how human gene variation in the same chemical pathways modulates the amygdala’s processing of threats and predicts how well people cope with stress.”

Studies are now needed to further explore both the connections between FAAH variation and PTSD risk as well as the potential of FAAH inhibition as a novel therapy for fear-related disorders, the researchers say.

More news from Duke University: http://today.duke.edu/

Scientists Link Rare Gene Mutations to Heightened Risk of Autism

Three teams of scientists working independently to understand the biology of autism have for the first time homed in on several gene mutations that they agree sharply increase the chances that a child will develop the disorder, and have found further evidence that the risk increases with the age of the parents, particularly the father.

The gene mutations are extremely rare and together account for a tiny fraction of autism cases, suggesting that the search for therapies will be a long one, and that what is loosely known as autism may represent a broad category of related but biologically distinct conditions.

There are likely hundreds, perhaps thousands, of rare mutations that could disrupt brain development enough to result in social and developmental delays.

But experts said that the overlapping results, reported in three papers posted online Wednesday in the journal Nature, give scientists working on the genetics of autism something they have not had: a clear strategy for building a real understanding of the disease’s biological basis.

Researchers hope to find more similar, rare mutations in the next year or so that they estimate could account for 10 percent to 20 percent of all cases.

Biologists have been groping in vain for a reliable, verifiable foothold from which to investigate the underlying genetics of so-called autism spectrum disorders, including Asperger syndrome and related social difficulties that are being diagnosed at alarmingly high rates — on average, in one of 88 children, according to a government estimate released last week.

Previous studies have produced a scattering of gene findings but little consensus or confidence in how to proceed.

The new work provides a measure of both, as well as strong backing for earlier studies linking autism to the age of new fathers.

“These studies aren’t so much a breakthrough, because we knew this was coming,” said Jonathan Sebat, a geneticist at the University of California, San Diego, who was not a part of the research teams.

“But I’d say it’s a turning point. We now have a reliable way forward, and I think it’s fair to expect that we will find 20, 30, maybe more such mutations in the next year.”

Other researchers were more cautious, saying that the genetics of rare mutations was not yet well enough understood to make conclusive statements about their effect on the behavior of specific genes.

“This is a great beginning, and I’m impressed with the work, but we don’t know the cause of these rare mutations, or even their levels in the general population,” said Dr. Aravinda Chakravarti, of the Institute of Genetic Medicine at the Johns Hopkins University Medical School, who was not involved in the studies.

“I’m not saying it’s not worth it to follow up these findings, but I am saying it’s going to be a hard slog.”

The three research teams took a similar approach, analyzing genetic material taken from blood samples of families in which parents who have no signs of autism give birth to a child who develops the disorder.

This approach gives scientists the opportunity to spot the initial mutations that accompany the condition, rather than trying to work though possible genetic contributions from maternal and paternal lines.

In all three studies, the researchers focused on rare genetic glitches called de novo mutations.

De novo mutations are not inherited but occur spontaneously near or during conception. Most people have at least one and the overwhelming majority of them are harmless.

Read more here: Scientists Link Rare Gene Mutations to Heightened Risk of Autism - NYTimes.com

Building brains: toward a do-it-yourself guide

With an estimated 100 billion neurons chattering to one another through perhaps a quadrillion synaptic connections, the human brain has the most intricately complicated structure and function of any object in the known universe.

How do you build something like that? In fact, how does something so ferociously complex start off as a single cell and then create itself?

The problem might at first seem impossible to fathom, even with the knowledge that genetics, natural selection, and a half billion years of evolution can accomplish amazing things. But complexity does not have to be born of complexity, as mathematics and computer programs routinely demonstrate.

Very simple equations can give rise to the stunning complexity of fractals, for example.

Several recent neuroscience studies may be illuminating some of the structural and development principles that organize the brain. Those principles include:

• Co-opting older, simpler genetic programs and elaborating on them to new effect.
• Maintaining geometric order.
• Relying on hierarchies of control.

True, science is still very far from knowing enough to define confidently how a brain takes shape (let alone how one works). Yet it’s still fascinating to see how much structure may be determined by relatively simple rules of thumb.

Rule 1: Elaborate on older genetic mechanisms
In the earliest stages of embryonic development, the nervous systems of vertebrate animals are much like those of simpler invertebrates such as worms and starfish.

The big differences start to appear as a result of actions by certain parts of the vertebrate embryo’s body called signaling centers.

These centers release proteins that tell portions of the embryo’s exterior layer of tissue (the neuroectoderm) to organize themselves into major divisions of what will eventually become brain and spinal cord.

The standing inference has been that the genes for those signaling proteins emerged as part of whatever evolutionary changes first split the vertebrate and invertebrate lines.

New work by Ariel M. Pani of the University of Chicago and others, recently published in Nature, suggests that is not the case, however.

The acorn worm Saccoglossus kowaleskii. (Credit: Ariel Pani)

Pani and her colleagues have identified a highly similar set of genes active in the acorn worm (Saccoglossus kowalevskii), a tiny aquatic invertebrate.

According to their studies, not only do these genes have sequences that echo those of the vertebrates but they also express themselves in a similar pattern and in corresponding parts of the body.

They also help to organize the formation of features in the worms’ ectodermal tissue layer.

What’s most curious about Pani’s findings — and makes them controversial — is that the acorn worms fall into the hemichordate branch of the invertebrate family, and as such are much more distant cousins to vertebrates than are many other creatures (such as sea squirts) that seem to lack these signaling center genes.

The implication is that the genes were present in some common wormy ancestor from about 500 million years ago but that the other lines of related invertebrates subsequently lost them during evolution.

Yet some biologists question both whether the genes are truly missing from the other invertebrates and whether they really serve to organize the acorn worms’ ectoderm to the sophisticated degree claimed. (Katherine Harmon at Scientific American reviews these disagreements.)

In either case, though, it seems likely that vertebrate evolution co-opted those ancient body-patterning genes and elaborated on their function to help kick off the formation of the vastly more complicated structures of the brain and spinal cord.

Rule 2: Stay on the grid

Diffusion spectrum MR image of human brain showing curvature of two-dimensional sheets of parallel neuronal fibers that cross each other at right angles. (Credit: Van Wedeen, M.D., Martinos Center for Biomedical Imaging, Massachusetts General Hospital)

Divvying the nascent nervous systems into segments is only the start, however.

Far trickier is the challenge of directing nerve cells to knit themselves into a networked structure complex enough to support all the capabilities we expect of a brain yet orderly enough to be compressed into a heritable developmental program.

An international research team led by Van J. Wedeen of Massachusetts General Hospital has now produced evidence that the overwhelming tangle of crisscrossing nerve fibers in the brain may obscure an underlying principle of organization that is surprisingly simple — and gridlike.

As Wedeen and his colleagues reported in the March 30 issue of Science, they mapped in detail the paths and intersections of major nerve tracts interconnecting different brain areas in humans and four other primates (rhesus monkeys, owl monkeys, marmosets, and galagos).

To do so, they used a technique called diffusion spectrum magnetic resonance imaging (DSI), which can track the movement of water molecules flowing through the neurons.

Image of rhesus monkey brain showing the sheet-like, three-dimensional structure of neural pathways that cross each other at right angles. (Credit: Van Wedeen, M.D., Martinos Center for Biomedical Imaging, Massachusetts General Hospital)

What they observed was that adjacent fibers running in parallel tended to be arranged into flattened, curving sheets, rather like the ribbon cables found in electronic devices.

Adding to the orderliness, these sheets of fibers crossed one another only at right angles. In effect, the fibers stayed aligned with the front-back, right-left, and top-bottom axes that frame the brain’s anatomical organization. (See Rose Eveleth’s news story about this work for Smart Planet.)

Wedeen’s work, too, has its skeptics. For instance, if the DSI technique happens to detect nerve fibers at right angles more easily than ones crossing more obliquely (which Wedeen seems to rule out), the exclusively orthogonal arrangement of the fiber sheets might be an illusion. (Ed Yong’s “Not Exactly Rocket Science” blog at Discover.com has an excellent rundown of the technical discussion.)

Nevertheless, the possibility of a gridlike design seems exciting. The discovery by Wedeen et al. doesn’t immediately explain how brain cells wire themselves together properly.

But it does suggest that some of the organizational principles in the spinal cord and brainstem, where fibers are very clearly arranged along those front-back, right-left, top-bottom axes, may extend forward into the forebrain, too.

Moreover, the findings hint at a system of “longitude and latitude for the brain,” as Wedeen says, about which some other scientists have previously speculated.

Orderly pathways and an implicit system of coordinates might make it much easier for neurons to navigate to their targets in specific brain areas.

Step 3: Respect the hierarchy!
The roughly 2.6 square feet of cortex covering the human brain is a folded quilt of specialized neural structures that each enable some of our capacities for thought, perception, decision making, and motor control.

Any anatomy student can spot the four major cortical lobes, but for a century and a half, since the time of psychiatrist Theodor Meynert, neuroscientists have been subdividing the cortex still further on the basis of cellular architecture.

Today, the number of subdivisions in the human cortex is more than a hundred, and the variations presumably reflect fine-grained differences in those areas’ functions.

The genetic controls for the development of those areas have nonetheless been obscure.

Chi-Hua Chen of the University of California, San Diego, and a group of collaborators have uncovered an interesting clue, however, as reported in last week’s issue of Science (alongside the Wedeen paper, in fact).

They looked at MRI scans of the brains of 406 adult twins enrolled in the Vietnam Era Twin Registry, an ongoing long-term study of cognitive aging.

From that data, they correlated how closely the size of various cortical surface areas corresponded to the degree of genetic similarity among the participants to find how much shared genetic influence there might be.

Genetic clustering map of the left human brain hemisphere, from Chen et al. (Credit: UC San Diego School of Medicine)

The result was what the scientists are calling the first “brain atlas of human cortical surface area that was based on genetic correlations, rather than a priori structural or functional information.”

Chen’s team identified 12 genetic subdivisions. The most exciting part, however, was that these genetic subdivisions corresponded very closely (though not always identically) to some of the traditional subdivisions neuroanatomists have recognized on the basis of function.

The pattern suggests that specific clusters of genes — all still to be identified — help to direct the formation of each of these specialized cortical areas.

The genetic program shaping the brain would thus be hierarchical, not unlike many computer programs.

That is, some general developmental program may guide overall cortical development up to a point, but then control is handed off to more specialized genetic routines within each area, which would sharpen that cortical region’s usefulness for one job.

Very possibly, within each of the genetic subdivisions that Chen’s group saw, further sets of genetic instructions kick in, too, and further refine smaller regions within the larger ones.

Such a scheme isn’t revolutionary: it’s what most biologists would probably tend to assume must take place, given hints of similarly nested control structures in other aspects of brain development.

Nevertheless, it’s reassuring to have some further direct evidence of it. As the German neuroscientists Karl Zilles and Katrin Amunts observed in their published commentary on the Chen and Wedeen papers in Science, “Hierarchical organization of the cortex is thus the unifying rule, which encompasses all scales from the molecular to the systems level.”

A future Rule 4? Mind the connections
The ultimate detail of structure within the brain that neuroscientists can seek is the precise pattern of synaptic connections among all the individual neurons.

Neuroscientists have started referring to a comprehensive catalog of all such linkages as the connectome.

As Carl Zimmer describes in his April column for Discover, the pursuit of the connectome is a stunningly audacious ambition. Current techniques for tabulating what connects with what in the brain are still slow and painstaking.

The data-keeping challenge alone might beggar belief: a map of all the synaptic connections within just a cubic millimeter of human brain tissue could fill a petabyte of storage.

Then again, perhaps as the connectome studies progress, some organizing principles for the distribution of synaptic connections will start to emerge, as they seem to be for some of the higher levels of structure.

Scientists like Sebastian Seung of M.I.T. are determined to go after the connectome in any case. For them, it is an unavoidable mystery, because that synaptic information could be the key to understanding how memory works, why people differ in intelligence, or what goes wrong in certain mental disorders.
Unless it isn’t.

Clearly, synaptic connections must be important to all neurological phenomena because synapses are what neurons use to send signals to one another. But maybe the ultrafine structure of precise synaptic connections will overshoot the level of structural detail needed to resolve those problems adequately, in the same way that doctors don’t need to know the precise position of every cell in your body to treat cancer.

Maybe the best and most useful answers about memory, intelligence, neurological disease and more will turn out to reside at a slightly higher (and more easily accessible) level of structure.

Prosopagnosia - Face Blidness

Prosopagnosia is a disorder of face perception where the ability to recognize faces is impaired, while the ability to recognize other objects may be relatively intact.

The term originally referred to a condition following acute brain damage, but a congenital form of the disorder has been proposed, which may be inherited by about 2.5% of the population.

The specific brain area usually associated with prosopagnosia is the fusiform gyrus.

Few successful therapies have so far been developed for affected people, although individuals often learn to use 'piecemeal' or 'feature by feature' recognition strategies.

This may involve secondary clues such as clothing, gait, hair colour, body shape, and voice. Because the face seems to function as an important identifying feature in memory, it can also be difficult for people with this condition to keep track of information about people, and socialize normally with others.

Some also use the term prosophenosia, which refers to the inability to recognize faces following extensive damage of both occipital and temporal lobes.

Children with Prosopagnosia
Developmental prosopagnosia can be a difficult thing for a child to both understand and cope with. Many adults with developmental prosopagnosia report for a long time they had no idea that they had a deficit in face processing, unaware that others could distinguish people solely on facial differences.

Children with prosopagnosia can be hard to find. They may just appear to be very shy or slightly odd due to their inabilities to recognise faces.

Children with prosopagnosia may have a hard time making friends, as they may not recognize their classmates. They often make friends with children with other distinguishing features.

Children with prosopagnosia may also have difficulties following the plots of television shows and movies, as they have trouble recognizing the different characters.

They tend to gravitate towards cartoons, where the characters always wear the same thing and have other distinguishing features.

Prosopagnosiac children may also have a hard time telling family members apart or recognizing people out of context (i.e. the teacher in a grocery store).

Additionally, those children with prosopagnosia can have a difficult time with the public school system, as many school professionals are not well versed in prosopagnosia, if they are aware of the disorder at all.

Resources
Resources to help parents and professionals cope with prosopagnosia in children are also being developed, such as Understanding Facial Recognition Disorders in Children by Nancy L. Mindick

Oliver Sacks, famous neuroscientist, author of many books including The Man Who Mistook His Wife for a Hat; although he knew what prosopagnosia was and had studied it, he did not realise he had it until people became shocked that he confused one of his brothers with the other and then, discussing it with family members, learned that a number of them had similar difficulties with face.

Dame Jane Goodall, British primatologist, ethologist, and anthropologist, best known for her 45-year study of social and family interactions of wild chimpanzees.

Study finds child abuse and stunted brain development connection

A small team of researchers has found that various forms of child abuse can lead to stunted development in certain regions of the brain. The research carried out by Martin Teicher, Carl Anderson and Ann Polcari, all working in the Boston area, relied on questionnaires.

MRI brain scans were used to determine that certain parts of the hippocampus, all known to be sensitive to stress, were up to six percent smaller in adults who as children had been sexually, verbally or physically abused. The team has published their results in the Proceedings of the National Academy of Sciences.

The three areas affected: the cornu ammonis, the dentate gyrus and the subiculum, all located in the hippocampus, are known to be vulnerable to stress which leads to less cell development than would normally occur in the absence of abuse.

To test the relationship between brain development and childhood abuse, the research team enlisted a group of otherwise healthy adult volunteers: 73 men and 120 women, all between the ages of 18 and 25.

All were given questionnaires that delved into their childhood, specifically addressing issues of verbal, mental and physical abuse and other types of stresses such as the death of someone close to them or problems between parents.

All were also given brain scans using an MRI machine. The team then compared the answers given on the questionnaires to the possibly impacted areas in the hippocampus of each volunteer. In so doing, they found that the brain regions under study were 5.8 to 6.5 percent smaller than average for those that reported such childhood stresses.

The researchers suggest that smaller brain regions due to childhood stress may help explain the abnormally high levels of mental illness (depression, bi-polarism, anxiety, etc.) seen in adults who have endured abuse as children and why so many wind up with drug dependency problems.

They also noted that one of the regions impacted, the subiculum, serves as a relay, moving information in and out of the hippocampus, which can have a direct impact on dopamine production. Those with reduced volume have been found to have problems with drug addiction and in some cases develop schizophrenia.

The researchers believe that increased stress leads to higher levels of the hormone cortisol, which in turn can slow or even stop the growth of new neurons in the brain which can result in permanently stunting certain brain regions.

The researchers are hoping their results will further highlight the damage that is done when children are subjected to adverse living conditions, leading perhaps to earlier interventions and possibly a means for developing treatments that may aid in preventing the stunting of brain regions, thus helping to pave the way for a better quality of life for those that have been abused as children.

More information: Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum, PNAS, Published online before print February 13, 2012, doi: 10.1073/pnas.1115396109

Abstract
Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side.

Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield.

The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer.

The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community.

Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores.

The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder.

Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively.

Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively.

These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.

Short-term memory is based on synchronized brain oscillations

In each of the two brain regions (IPF and V4) brain activity shows strong oscillations in a certain set of frequencies called the theta-band.

Credit: Stefanie Liebe, MPI for Biological Cybernetics

Holding information within one's memory for a short while is a seemingly simple and everyday task.

We use our short-term memory when remembering a new telephone number if there is nothing to write at hand, or to find the beautiful dress inside the store that we were just admiring in the shopping window.

Yet, despite the apparent simplicity of these actions, short-term memory is a complex cognitive act that entails the participation of multiple brain regions.

However, whether and how different brain regions cooperate during memory has remained elusive.

A group of researchers from the Max Planck Institute for Biological Cybernetics in Tübingen, Germany have now come closer to answering this question.

They discovered that oscillations between different brain regions are crucial in visually remembering things over a short period of time.

It has long been known that brain regions in the frontal part of the brain are involved in short-term memory, while processing of visual information occurs primarily at the back of the brain.

However, to successfully remember visual information over a short period of time, these distant regions need to coordinate and integrate information.

To better understand how this occurs, scientists from the Max Planck Institute of Biological Cybernetics in the department of Nikos Logothetis recorded electrical activity both in a visual area and in the frontal part of the brain in monkeys.

The scientists showed the animals identical or different images within short intervals while recording their brain activity. The animals then had to indicate whether the second image was the same as the first one.

The scientists observed that, in each of the two brain regions, brain activity showed strong oscillations in a certain set of frequencies called the theta-band.

Importantly, these oscillations did not occur independently of each other, but synchronized their activity temporarily: "It is as if you have two revolving doors in each of the two areas.

During working memory, they get in sync, thereby allowing information to pass through them much more efficiently than if they were out of sync," explains Stefanie Liebe, the first author of the study, conducted in the team of Gregor Rainer in cooperation with Gregor Hörzer from the Technical University Graz.

The more synchronized the activity was, the better could the animals remember the initial image. Thus, the authors were able to establish a direct relationship between what they observed in the brain and the performance of the animal. 

New automated imaging greatly speeds up brain mapping

3-D rendering of coronal section of a mouse brain imaged with STP tomography at 20x at a resolution of half a micron.

GFP-expressing pyramidal neurons in hippocampus and cortex are targeted.

A new technology developed by neuroscientists at Cold Spring Harbor Laboratory (CSHL) transforms the way highly detailed anatomical images can be made of whole brains.

Until now, means of obtaining such images – used in cutting-edge projects to map the mammalian brain -- have been painstakingly slow and available only to a handful of highly specialized research teams.

By automating and standardizing the process in which brain samples are divided into sections and then imaged sequentially at precise spatial orientations in two-photon microscopes, the team, led by Assoc. Prof. Pavel Osten and consisting of scientists from his CSHL lab and the Massachusetts Institute of Technology, has opened the door to making whole-brain mapping routine.

Specifically, says Osten, "the new technology should greatly facilitate the systematic study of neuroanatomy in mouse models of human brain disorders such as schizophrenia and autism."

The new technology, developed in concert with TissueVision of Cambridge, Mass. and reported on in a paper appearing online Jan. 15 in Nature Methods, is called Serial Two-Photon Tomography, or STP tomography.

Tomography refers to any process (including the familiar CAT and PET scans used in medical diagnostics) that images an object section by section, by shooting penetrating waves through it.

Computers powered by mathematical formulae reassemble the results to produce a three-dimensional rendering. Two-photon imaging is a type used in biology laboratories, particularly in conjunction with fluorescent biomarkers, which can be mobilized to illuminate specific cell types or other anatomical features.

The two-photon method allows deeper optical penetration into the tissue being sampled than conventional confocal microscopy.

As Osten explains, STP tomography achieves high-throughput fluorescence imaging of whole mouse brains via robotic integration of the two fundamental steps -- tissue sectioning and fluorescence imaging. In their paper, his team reports on the results of several mouse-brain imaging experiments, which indicate the uses and sensitivity of the new tool.

They conclude that it is sufficiently mature to be used in whole-brain mapping efforts such as the ongoing Allen Mouse Brain Atlas project.

One set of experiments tested the technology at different levels of resolution. At 10x magnification of brain tissue samples, they performed fast imaging "at a resolution sufficient to visualize the distribution and morphology of green-fluorescent protein-labeled neurons, including their dendrites and axons," Osten reports.

Multiple Sclerosis research links brain activity to steep Cognitive decline

When it comes to communication in the brain, more is usually better but now scientists have linked increased communication in a network of brain regions to more severe mental impairment in patients with early-stage multiple sclerosis (MS).

“Measuring how well this network’s connections are working may provide a way to look beyond the wide-ranging symptoms of MS to help us quantify the disorder’s effects on the brain,” says co-author Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology at Washington University School of Medicine in St. Louis.

“This assessment could be very useful in diagnosing the disease and tracking the effectiveness of new treatments.”

Scientists at Washington University and the University Medical Center at Hamburg-Eppendorf and the University of Tübingen, both in Germany, published the results in the Proceedings of the National Academy of Sciences.

MS damages brain cell branches, impairing the cells’ ability to communicate. The disease is highly unpredictable and produces a hodgepodge of symptoms that vary from patient to patient. These include fatigue, numbness, dizziness, pain, bowel and bladder dysfunction, visual impairments, speech disorders, headache, depression and problems with balance, coordination and walking.

The brain can redirect energy and resources to make it possible for more signals to flow through damaged circuits. But in MS, the researchers speculate, that redirection may lead to a decrease in the brain’s ability to reconfigure itself for different cognitive tasks, such as speaking, processing sensory information, controlling movement, regulating mood and creating and accessing memory.

The current study focused on whether correlations could be made between the structural damage caused by MS, the cognitive problems experienced by patients and changes in brain networking, which refers to the ability of various regions in the brain to work with each other.

The study involved 16 patients who had been diagnosed with MS in the previous four years. For comparison, scientists also included 16 healthy individuals. All participants were given an extensive battery of behavioral and cognitive tests, as well as brain scans to look for structural damage. Researchers also evaluated the connectedness of brain regions that often work together in networks.

MIT Neuro-Scientists Prevent the Formation of Long-Term Memory

Neuroscientists at the Massachusetts Institute of technology (MIT) have found a way to "prevent the formation of long- term memory".They achieved this by deactivating Npas4, a memory gene.

When a person experiences a new event, his or her brain encodes it as a memory by altering the connections between the neurons, and the neurons turn on many genes.

The scientists found a way to control this process by deactivating the Npas4.

The MIT scientists conducted experiments on mice to achieve this. They sent the mice to a chamber. When the mice entered the chamber for the first time, they received a slight electric shock.

This frightened the mice, and the fear activated the Npas4. However, the scientists could prevent the formation of the long-term memory of this bad experience by deactivating the Npas4.

Yingxi Lin, a member of the Mc Govern Institute for Brain Research, who led the study, said that they had deactivated the gene by "deleting the gene from the genome".

"Our research showed that deletion of Npas4 prevents the formation of long-term memory. We don't have any data showing its role in memory erasure. Just want to clarify that," she said.

Her clarification came in the wake of some reports in the media which suggested that the MIT scientists had found a way to "erase memory".

When asked about how the method could be used in humans and its possible application in treating mental diseases, Lin said: "This is basic research. In the long run, it will help us understand the mechanisms of learning and memory in humans, which can potentially help treating mental disorders."

Our brains get confused when we're anxious

Competing neurons in this part of the brain help us make decisions, such as choosing words. (Credit: Image courtesy of Marie Banich)

A new University of Colorado at Boulder study sheds light on the brain mechanisms that allow us to make choices and ultimately could be helpful in improving treatments for the millions of people who suffer from the effects of anxiety disorders.

In the study, CU-Boulder psychology Professor Yuko Munakata and her research colleagues found that "neural inhibition," a process that occurs when one nerve cell suppresses activity in another, is a critical aspect in our ability to make choices.

"The breakthrough here is that this helps us clarify the question of what is happening in the brain when we make choices, like when we choose our words," Munakata said.

"Understanding more about how we make choices, how the brain is doing this and what the mechanisms are, could allow scientists to develop new treatments for things such as anxiety disorders."

Researchers have long struggled to determine why people with anxiety can be paralyzed when it comes to decision-making involving many potential options.

Munakata believes the reason is that people with anxiety have decreased neural inhibition in their brain, which leads to difficulty making choices.

"A lot of the pieces have been there," she said. "What's new in this work is bringing all of this together to say here's how we can fit all of these pieces of information together in a coherent framework explaining why it's especially hard for people with anxiety to make decisions and why it links to neural inhibitors."

A paper on the findings appeared in the Aug. 30 Proceedings of the National Academy of Sciences.

CU-Boulder professors Tim Curran, Marie Banich and Randall O'Reilly, graduate students Hannah Snyder and Erika Nyhus and undergraduate honors thesis student Natalie Hutchison co-authored the paper.

In the study, they tested the idea that neural inhibition in the brain plays a big role in decision-making by creating a computer model of the brain called a neural network simulation.

"We found that if we increased the amount of inhibition in this simulated brain then our system got much better at making hard choices," said Hannah Snyder, a psychology graduate student who worked with Munakata on the study.

"If we decreased inhibition in the brain, then the simulation had much more trouble making choices."

Through their model they looked at the brain mechanisms involved when we choose words. They then tested the model's predictions on people by asking them to think of the first verb that comes to mind when they are presented with a noun.

Brain function - A new way to measure the burden of aging

Cognitive function may be a better indicator of the impact of aging on an economy than age-distribution, with chronological age imposing less of a social and economic burden if the population is "functionally" younger, according to a study published today in the Proceedings of the National Academy of Sciences.

The study finds that one standardized indicator of cognitive ability - memory recall - is better in countries where education, nutrition, and health standards are generally higher.

Aging populations are of concern to many countries as it is often assumed that aging necessarily implies a greater cost to society in terms of aged care, age related disease, and reduced capacity to contribute to society.

However this research suggests that the effects of chronological aging are uneven across nations and that in some countries, particularly more affluent ones that are able to invest in early and sustained education and health programs, cognitive function and thus the ability to live healthy, productive lives, is maintained longer.

"Demographic indicators of the economic impact of an aging population typically rely on measures based on populations' age-distribution, expressed as the Old Age Dependency Ratio (OADR).

Whilst this is helpful measurement it does not include information on individual characteristics, other than age," says lead author Vegard Skirbekk from the International Institute for Applied Systems Analysis (IIASA).

"We believe cognitive function can provide a new and comparable measure of how a region or a nation's population may age. Such information can inform early intervention in the education and health systems to try and improve cognitive performance, ultimately reducing the burden of aging."

"For example, in northern Europe or the United States where there is a relatively large population over the age of 65, we found that cognitive function is higher for this age group than for the same age group in Mexico, India and China. Overall, even though Europe and the US may be chronologically older they are 'functionally' younger."

Cognitive ability levels are also good indicators of individual productivity and this has direct relevance to the economic and business activities within a country.

The authors suggest that the difference in cognitive function may be explained by the fact that seniors in some regions of the world experience better conditions during their childhood and adult life; including nutrition, duration and quality of schooling, exposure to disease, and physical and social activity.

EEG finds consciousness in people in vegetative state

Signs of consciousness have been detected in three people previously thought to be in a vegetative state, with the help of a cheap, portable device that can be used at the bedside.

"There's a man here who technically meets all the internationally agreed criteria for being in a vegetative state, yet he can generate 200 responses [to direct commands] with his brain," says Adrian Owen of the University of Western Ontario.

"Clearly this guy is not in a true vegetative state. He's probably as conscious as you or I are."

In 2005, Owen's team, used functional MRI to show consciousness in a person who was in a persistent vegetative state (PVS), for the first time.

PVS is also known as 'wakeful unconsciousness', whereby the body still functions but the mind is unresponsive.

However, fMRI is costly and time-consuming, so his team set about searching for simple and cost-effective solutions for making bedside diagnoses of PVS.

Now, they have devised a test that uses the relatively inexpensive and widely available electroencephalogram (EEG).

An EEG uses electrodes attached to the scalp to record electrical activity in the brain.

Imagine wiggling your toes
Owen and his team used an EEG on 16 people thought to be in a PVS and compared the results with 12 healthy controls while they were asked to imagine performing a series of tasks.

Each person was asked to imagine at least four separate actions – either clenching their right fist or wiggling their toes.

In three of the people with PVS, brain regions known to be associated with those tasks lit up with activity, despite physical unresponsiveness.

This suggested to the researchers that the subjects were carrying out a complex set of cognitive functions including hearing the command, understanding language, sustaining attention and tapping into working memory.

"It isn't the case that just because somebody doesn't respond they're not conscious," Owen says. "There's a growing body of data now demonstrating that many of these patients aren't what they appear."

Criteria of Vegetative State (PVS)
"The diagnostic criteria for vegetative state have to change," he adds. The official diagnosis for PVS was formulated in the 1970s, before neuro-imaging was widely used, says Owen.

The last update was made in 1995, but the criteria for declaring someone conscious is still based on whether an outside observer believes the patient is trying to communicate.

Morten Overgaard, a cognitive neuroscientist at Aalborg and Aarhus University in Denmark, says that determining whether Owen's patients are actually responding consciously or whether they are unconsciously reacting to suggestions from the command is difficult to know without further study.

"If this is suggested as a standalone test to decide whether a person is conscious or not, then we need [signs] that are very strong and not just an indication of consciousness," he says.


Absence of Awareness
The test cannot prove the absence of awareness, but it can identify people who weren't thought to be conscious, says Damian Cruse, a collaborator on the study.

This was particularly apparent when 25 per cent of the healthy controls returned EEG readings that were below expected levels of conscious thought.

Communicating with carers
However, for those people previously considered to be unaware of their surroundings, communicating with their caretakers through EEG tests could change their life. "We're trying to work out how to use this technique to find out more about somebody's internal mental state," says Owen. "It opens up the possibilities for potentially facilitating recovery. If you have a channel of communication with a patient, you can have that patient play a role in therapeutic intervention."

Parasite directly alters brain chemistry

A research group from the University of Leeds has shown that infection by the brain parasite Toxoplasma gondii, found in 10-20 per cent of the UK’s population, directly affects the production of dopamine, a key chemical messenger in the brain.

Their findings are the first to demonstrate that a parasite found in the brain of mammals can affect dopamine levels.

Whilst the work has been carried out with rodents, lead investigator Dr. Glenn McConkey of the University’s Faculty of Biological Sciences, believes that the findings could ultimately shed new light on treating human neurological disorders that are dopamine-related such as schizophrenia, attention deficit hyperactivity disorder, and Parkinson’s disease.

This research may explain how these parasites, remarkably, manipulate rodents’ behaviour for their own advantage. Infected mice and rats lose their innate fear of cats, increasing the chances of being caught and eaten, which enables the parasite to return to its main host to complete its life cycle.

In this study, funded by the Stanley Medical Research Institute and Dunhill Medical Trust, the research team found that the parasite causes production and release of many times the normal amount of dopamine in infected brain cells.

Dopamine is a natural chemical which relays messages in the brain controlling aspects of movement, cognition and behaviour. It helps control the brain’s reward and pleasure centres and regulates emotional responses such as fear. The presence of a certain kind of dopamine receptor is also associated with sensation-seeking, whereas dopamine deficiency in humans results in Parkinson’s disease.

These findings build on earlier studies in which Dr. McConkey’s group found that the parasite actually encodes the enzyme for producing dopamine in its genome.

“Based on these analyses, it was clear that T. gondii can orchestrate a significant increase in dopamine production in neural cells,” says Dr. McConkey.

“Humans are accidental hosts to T. gondii and the parasite could end up anywhere in the brain, so human symptoms of toxoplasmosis infection may depend on where parasite ends up. This may explain the observed statistical link between incidences of schizophrenia and toxoplasmosis infection.”

Dr. McConkey says his next experiments will investigate how the parasite enzyme triggers dopamine production and how this may change behaviour.

Why hearing aids fail

Hearing aids have improved greatly over recent years, but they continue to be a surprisingly frustrating experience for new wearers.

Clearly, today’s hearing aids are tiny, nearly invisible in fact, and they amplify sound and are able to present a higher range of frequencies, but they have not yet completely solved the problem of amplifying the peripheral sounds we just don’t want, or don't need to hear.

For new wearers the crumpling of a paper bag on the other side of a room can sound like a jackhammer.

This is a huge challenge for technology because it is dependent on how the brain perceives sound and how we have learned to filter peripheral sound out of normal hearing. Andrew J. Oxenham is a psychologist and hearing expert at the University of Minnesota and an expert in psychoacoustics.

Oxenham explains: The ear works by analysing sound and breaking it into different frequencies and with many forms of hearing impairment it’s this frequency selectivity that is impaired.

What that means is that the ear doesn’t filter as well as it did before. So instead of having very sharp tuning to filter out different frequencies the filtering becomes much broader and there is no real way of compensating for that.

You can’t sharpen the filters or you can’t pre-process sound so it’s sharp. It’s like a broken TV set. You can process the signal going into the TV as much as you like but you still won’t get a clear picture of the output.

Recent hearing aids have made a lot of progress, like being able to present frequencies of up to 6000 Hz as opposed to limited frequencies up to about 4000 Hz, by using digital signal processing, and a lot more computing power on a lot smaller chip.

Another big leap forward has been made with directional hearing. They can focus the microphones toward the front and filter out a lot of the sound coming from the side and back. And although that is a fairly simple technique, it involves signal processing that wasn’t possible with earlier hearing aids.

Ambient or peripheral sound is horribly distracting for hearing aid wearers. A paper bag being crumpled across a room sounds screechingly loud.

This is common complaint of people who recently start wearing a hearing aid. Their hearing has deteriorated, often without them being completely aware of it, over a period of time.

When they are suddenly fitted with a hearing aid, they hear sounds they’ve got used to not hearing. The sounds are suddenly annoying and distracting. It’s a contrast effect.

It’s more to do with perception i.e the brain’s ability to analyse and prioritise different sounds.

It’s a complex interaction between the ear and the brain. The ear sends signals up to the brain; the brain does an awful lot of processing on top of that; then sends signals back down to the ear. These signals change the way the ear accepts input.

This is partly why hearing aids are not perfect because the hearing aid is not part of that natural feedback loop. There’s no way with current aids that the brain can interface with a hearing aid directly to change its characteristics.

Hearing Loops
To deal with background noise there are things called “hearing loops.”

These are systems that are set up within places like concert halls and churches that interface directly with the hearing aid. It’s like sending a radio signal to the hearing device.

The idea is that this hearing loop picks up the sound directly from the microphone in front of a speaker.

If you are in a conference and the speaker is talking into a microphone. Normally we hear the sound acoustically through the airwaves.

If you are wearing a regular hearing aid the microphone will pick up the sounds on the airwaves but that is together with all the background noise and reverberation in the room.

With a hearing loop it sends the signal directly from the microphone to the ear and bypasses all the acoustics in the building itself. So the ear is getting a much better, clearer and cleaner signal of what’s coming into the microphone.

Two hearing aids better than One?
It’s only recently that people have routinely been fitted with two hearing aids. Often people only got one.

Directional hearing and the way we localise sound: To know where the sound is coming from the brain compares the signals coming into the two ears. So if it’s slightly louder on one side then the brain knows the sound is coming from that side.

More importantly it’s the time of arrival difference between the two ears. If you think about a sound coming from the right. The sound will reach your right ear a little bit before it reaches your left ear.

Although we are talking about millionths of seconds, your brain needs two ears to make a distinction. If you only have one you lose that ability to localise sound and tell which direction it is coming from.

It’s also an important part of filtering out sound and noise. The brain can determine if there is speech right in front and background noise in back of and to the side. The brain can use those differences in localisation to help to make the speech more intelligible.

So the biggest technical challenge is developing hearing aids that can focus on what we really need and want to listen to. This is the current problem.

The Solution
We are hoping through even more sophisticated signal processing schemes that we’ll be able to work on artificial source segregation; i.e. analysing the signal that is coming in and figuring out what is speech and what isn’t, and only presenting to the ear the wanted signal.

Distinguishing between speech and noise
The assumption is that what you really want to listen to is speech, and so there are certain acoustical aspects of speech that we can recognise and there are certain acoustical aspects of noise that are different from speech.

So, we need to establish a suitable algorithm to be able to distinguish between speech and noise that will help you towards filtering the unwanted signal.

A more complete solutiion could mean that brain-computer interface may be part of the hearing aid systems of the future. Where the hearing aid is tapping into brain responses to pick up the specific signal the person wants to pay attention to.

This is an ongoing process with incremental steps and we will continue to see improvements over the next 15 years.

Scientists find they can control how people react to group pressure

Researchers found they were able to control whether volunteers conformed to social pressure by using powerful electromagnetic pulses that changed the activity of a small part of the brain.

Volunteers whose posterior medial frontal cortex, an area in the middle of the brain that is associated with reward processing, were exposed to the magnetic pulses suffered reduced levels of conformity.

The researchers believe this part of the brain dates back a long way in the evolution of animals and is responsible or automatically "correcting" our performance when we fall out of line with a group.

They say that by suspending this mechanism, it allows people to think and behave differently. They now believe it may be possible to develop drugs or behaviour changing techniques that could increase or decrease people's conformity.

Dr Vasily Klucharev, a neuroscientist who led the research at the Radboud University Nijmegen, in Holland, said: "People can try to reduce conformity in certain situations, especially when they know about negative consequences of group pressure such as criminal behaviour, propaganda or aggressive marketing.

"Right now we can search for behavioural techniques that modulate activity of the posterior medial frontal cortex without any physical intervention. Hopefully, with help of these techniques someone would be able to partly immune themselves to 'group pressure'.

"Drug manipulation of dopamine could also affect conformity."

Such drugs would be controversial, however, as they could be used by companies hoping to make their employees more reliable or to help control rebellious individuals.

In the study, the researchers asked 49 female volunteers to take part in a study where they were asked to rate the attractiveness of 220 photographs of female faces, but they were allowed to change their ratings after seeing what others in the study had scored.

When Transcranial Electromagnetic Stimulation (TMS) was used to inhibit the activity of the neurons in the posterior medial frontal cortex, the participants did not change their ratings of the photographs so they were more in line with the rest of the group.

Dr Klucharev believes this part of the brain is responsible for generating an "error" signal when individuals deviate from the group opinion, triggering a cascade that leads them to conform with the group view.

He said: "What if that mechanism could be suspended for a time? The group who were exposed to the TMS changed their views to a much lesser extent – they were immune to 'group pressure'.

"Individuals differ in the strength of the error signal – which is why some people are more conformist than others. It also tells us that conformity is a rather automatic process that is based on an old evolutionary mechanism."

Molly Birnbaum - When all you can smell is your brain

In the summer of 2005 Molly Birnbaum was out jogging near her home in Brookline Massachusetts when she was hit by a car.

The impact fractured her skull and severed her olfactory nerves, leaving her without a sense of smell.

The prognosis was bad - Birnbaum was told she would never smell again. Depressed and deprived of her sense of smell, and therefore taste, she was forced to give up her place at culinary college and with it, her ambitions of becoming a chef.

Instead of resigning herself to living without scent, Birnbaum ended up on a quest to find out more about this mysterious sense, and eventually got her sense of smell back.

She tells this story in her book Season to Taste.

I started to get a few scents back one at a time, slowly but very attached to memory and emotion. As that went on I began to be very curious as to what was going on in my nose, in my brain, how come I didn't know anything about the sense of smell even though it so affected my life.

So I began to talk to scientists and doctors about the science of smell. I spoke with chefs and perfumers and I spent time in a flavour lab in New Jersey, I went to a perfume school in France, and spent time with neurologist Oliver Sacks and really tried to explore what it means to smell.

A little while after the accident I was helping my mother to cook dinner. I was chopping a bunch of fresh rosemary, and all of a sudden this smell hit me out of nowhere. It had been so long since I had smelt anything I was shocked. It was just this glorious scent of herbs and earthy rosemary and it reminded me of my childhood. It gave me a lot of hope.

At one point i became convinced i could smell my own brain. This was very disturbing. One common thing when people lose their sense of smell is to experience phantom smells - smells that don't actually exist from a concrete source in reality. I have met people who have had horrible ones - rotting smells, or garlic smells when they are trying to eat a fresh peach - but for me it was much more subtle.

Towards the beginning of my experience I could smell this one smell all the time. The only way I could make sense of it was that this smell was coming from within me, that it was probably my brain. It was one of the stories I told myself to make sense of this experience.

I think what I really lost was the emotional component to certain memories, the memories we have when we smell something familiar and are immediately transported back to a moment in our past - kind of like a punch in the gut emotion. When I couldn't smell I could still remember these events, I just didn't have that punch in the gut. And I worried about how, if I could never smell again, that would affect the memories that I should be making in the future.

How memory is lost — and re-found

A new study published July 27 in the journal Nature shows that the neural networks in the brains of the middle-aged and elderly have weaker connections and fire less robustly than in youthful ones.

Intriguingly, note the scientists, the research suggests that this condition is reversible.

“Age-related cognitive deficits can have a serious impact on our lives in the Information Age, as people often need higher cognitive functions to meet even basic needs, such as paying bills or accessing medical care,” says Amy Arnsten, professor of neurobiology and psychology and a member of the Kavli Institute for Neuroscience.

“These abilities are critical for maintaining demanding careers and being able to live independently as we grow older.”

Arnsten and her team studied the firing of prefrontal cortical neurons in young, middle-aged and old animals as they performed a working memory task. Neurons in the prefrontal cortex of the young animals were able to maintain firing at a high rate during working memory, while neurons in older animals showed slower firing rates.

However, when the researchers adjusted the neurochemical environment around the neurons to be more similar to that of a younger subject, the neuronal firing rates were restored to more youthful levels.

Arnsten says that the aging prefrontal cortex appears to accumulate excessive levels of a signaling molecule called cAMP, which can open ion channels and weaken prefrontal neuronal firing. Agents that either inhibited cAMP or blocked cAMP-sensitive ion channels were able to restore more youthful firing patterns in the aged neurons.

One of the compounds that enhanced neuronal firing was guanfacine, a medication that is already approved for treating hypertension in adults and prefrontal deficits in children, suggesting that it may be helpful in the elderly as well, note the researchers.

Arnsten’s finding is already moving to the clinical setting. Christopher vn Dyck of the Yale School of Medicine is enrolling subjects in a clinical trial testing guanfacine’s ability to improve working memory and executive functions in elderly subjects who do not have Alzheimer’s disease or other dementias.

Information about the clinical trial can be found online,