Despite the aches and pains that occur in old age, many older adults maintain a positive outlook, remembering the positive experiences from their past. A new study, reported in the April 2010 issue of Elsevier’s Cortex, reveals that older adults’ ability to remember the past through a positive lens is linked to the way in which the brain processes emotional content. In the older adult brain, there are strong connections between those regions that process emotions and those known to be important for successful formation of memories, particularly when processing positive information.

Dr Donna Rose Addis from the University of Auckland, together with a team of researchers supervised by Dr. Elizabeth A. Kensinger of Boston College (Chestnut Hill, MA), asked young adults (ages 19-31) and older adults (ages 61-80) to view a series of photographs with positive and negative themes, such as a victorious skier or a wounded soldier. While participants viewed these images, a functional magnetic resonance imaging (fMRI) scan recorded the brain activity across a number of different regions. When participants had completed the fMRI scan, they were asked to remember as many of the photographs as they could.

Analyses revealed that aging did not affect the connectivity among regions engaged during memory formation for negative photographs. However, age differences did arise during the creation of memories for positive photographs. In older adult brains, two regions that are linked to the processing of emotional content the ventromedial prefrontal cortex (a region located just behind the bridge of the nose) and the amygdala (a region embedded in the tissue between the ears) were strongly connected to regions that are linked to memory formation. In young adults, there was not a strong connection between the emotion-processing regions and the memory-creation regions.

These findings suggest that older adults remember the good times well, because the brain regions that control the processing of emotions act in concert with those that control the processing of memory, when older adults experience positive events. Young adults lack these strong connections, making it harder for them to remember positive experiences over the long term.

Children with brain injuries may use gesture to signal they need help in developing language, research at the University of Chicago shows. The children who make the fewest gestures early in development also develop spoken vocabulary more slowly.

A research team studied 11 children with brain lesions, areas of damaged tissue, to determine the relationship between gesture and language development. They compared the children’s development to language development in 53 children without brain injuries.

Researchers found that eight of the 11 children with brain injuries had vocabulary development below the 25th percentile at 18 months, but only five of the children still had delayed language development four months later.

“The striking result of our study is that these five children with language delays were the same five who were low gesture producers at 18 months,” said Susan Goldin-Meadow, the Beardsley Ruml Distinguished Service Professor in Psychology and an expert on gesture.

“Thus early gesture may provide clinicians with a way to identify children who may end up having persistent language difficulties, even before those difficulties appear in the children’s speech,” she added. “Our results also raise the possibility that encouraging children with brain lesions to gesture may prove an effective intervention to prevent language delay.”

Goldin-Meadow is an author of the paper, “Early Gesture Predicts Language Delay in Children with Pre- or Perinatal Brain Lesions,” published in the March issue of Child Development, along with lead author Eve Sauer, a University researcher, and Susan Levine, the Stella M. Rowley Professor in Psychology.

The team studied 11 children from age 18 months to 30 months. All of the children had suffered brain injuries prenatally or during birth.

The children were observed in their homes three times a year for 90 minutes while they interacted with their primary caregivers in normal, everyday activities. Researchers tape-recorded the interactions, which included children’s gestures and their speech.

Although as a group the children with lesions produced as many gestures as the typically developing children, “there was a great deal of variability within the group of children with pre- and perinatal brain lesions,” Sauer said. Of the 11 children in the sample, five were found to be using many fewer gestures.

“At 18 months, it was not possible to reliably distinguish the two groups on the basis of their speech use, only their gesture use,” Levine said. The five children who used fewer gestures later had delayed language development, she said.

Other research, including work by Goldin-Meadow, has shown a strong relationship between gesture and language development in children without brain injuries. The new research shows that this relationship also exists in children with early brain lesions.

Gesture reflects the speed at which children develop language, but gesture may play a role in speeding up language development, Goldin-Meadow said. For example, parents may respond to a child’s pointing at an object by providing a label for the object. This would give the child just the right linguistic input at just the right moment.

It will be harder to lie about your age or your poker hand after new research by the University of Melbourne, Australia has revealed that our eye position betrays the numbers we are thinking about.

In the study, participants were asked to state a series of random numbers. By measuring their vertical and horizontal eye position, researchers were able to predict with reliable confidence the next chosen number – before it was spoken.

Specifically, a leftward and downward change in eye position announced that the next number would be smaller than the last. Correspondingly, if the eyes changed position to the right and upward, it forecast that the next number would be larger. The degree of eye movement reflected the size of the numerical shift.

The paper was published online in the prestigious journal Current Biology.

First author, Dr Tobias Loetscher of the University of Melbourne’s School of Behavioural Sciences and previously of the Department of Neurology, University Hospital Zurich, Switzerland says the research demonstrates how the eyes and their position give insight into the nature of the systematic choices made by the brain’s random number generator.

“When we think of numbers we automatically code them in space, with smaller number falling to the left and larger numbers to the right. That is, we think of them along a left-to-right oriented mental number line – often without even noticing this number-space association ourselves.”

“This study shows that shifts along the mental number line are accompanied by systematic eye movements. We suggest that when we navigate through mental representations – as for example numbers – we re-use brain processes that primarily evolved for interacting and navigating in the outside world.”

Dr Michael Nicholls also of the School of Behavioural Sciences adds, “Clearly, the eyes not only allow us to see the world around us, but they also present a window to the working of our mind, as this study shows.”

“This study will hopefully provide a template to investigate how the human mind works via a connection with the space and world around us,” he says.

The study involved asking twelve right-handed men to select from a set of random numbers. Paced by an electronic metronome they named 40 numbers between 1 and 30 in a sequence as random as possible. For each number, the researchers measured the average eye position during the 500 millisecond interval before the numbers were stated.

In one of the first such studies involving human patients with schizophrenia, researchers at UC Davis have provided evidence that deficits in a brain chemical may be responsible for some of the debilitating cognitive deficits – poor attention, memory and problem-solving abilities – that accompany the delusions and hallucinations that are the hallmarks of the disorder.

The study, published online in the Journal of Neuroscience, suggests an important avenue of inquiry for improving cognitive function in the more than 2 million Americans who suffer from schizophrenia, according to Jong H. Yoon, an assistant professor of psychiatry and behavioral sciences at UC Davis Health System and the study’s lead author.

“We still know very little about the neurobiology of schizophrenia, particularly at the level of specific circuits and molecules and how their impairments affect behavior and cognition in the disease,” said Yoon, a researcher at the UC Davis Imaging Research Center. “We need this level of specificity to guide targeted treatment development. This is one of the first studies to show that there is a strong association between cognitive deficits and a decrease in a particular neurotransmitter.”

Schizophrenia is characterized by psychosis – abnormalities in the perception or expression of reality. Sufferers may experience visual or auditory hallucinations and have paranoia, delusions and disorganized speech and thinking. But they also experience profound cognitive difficulties that interfere with daily functioning.

Psychosis is treated with a variety of antipsychotic medications that dampen overactivity of the neurotransmitter dopamine, an acknowledged cause of psychotic behavior. But no medications are available to address cognitive deficits in schizophrenia because the source of the deficits has not been determined. Deficits in one brain chemical, the neurotransmitter gamma-aminobutyric acid, or GABA, have been implicated as playing a causal role in cognitive difficulties in people with schizophrenia in research involving animal models and post-mortem analyses of GABA concentrations in human schizophrenic brains.

“People think of schizophrenia as being related to psychosis. But patients’ cognitive limitations can be even more debilitating for them,” said Cameron Carter, professor of psychiatry and behavioral sciences, director of the Imaging Research Center and the study’s senior author. “This study actually looked at brain chemistry in live patients in relation to cognitive performance to determine the underlying neurobiology of the cognitive deficits. Our ultimate goal is discovering ways to help patients lead more productive lives.”

Yoon and his colleagues measured the levels of GABA in the visual cortexes of the brains of 13 study subjects with schizophrenia and 13 control subjects without the disorder. The measurements were conducted with high-field magnetic resonance spectroscopy, a technique that involves using a magnetic resonance imaging scanner to examine neurotransmitter activity. The schizophrenic patients were found to have a deficit in GABA of about 10 percent when compared with their non-schizophrenic counterparts.

The second half of the study involved demonstrating the significance of the neurochemical deficit on cognition and behavior. To do this the researchers measured the visual perception of the subjects for whom GABA levels were assessed by showing them a well-known illusion in which the presence of a high-contrast surrounding region inhibits the ability to perceive information in the center of the visual field.

The researchers showed that this surround-suppression illusion had less of an effect on patients with schizophrenia, resulting in a highly unusual situation in which they outperformed healthy subjects when baseline differences in generalized task performance were accounted for. The researchers then found that the lower levels of GABA in patients were responsible for this behavioral abnormality.

“The link between changes in patients’ brain chemistry and the cognitive impairments they experience never has been shown before in this way,” Carter said. “This work provides tremendous support for targeting the GABA system for treatment of cognitive decline in schizophrenia.”

Common wisdom tells us that for a successful relationship partners shouldn’t go to bed angry. But new research from a psychologist at Harvard University suggests that brain activity – specifically in the region called the lateral prefrontal cortex – is a far better indicator of how someone will feel in the days following a fight with his or her partner.

Individuals who show more neural activity in the lateral prefrontal cortex are less likely to be upset the day after fighting with partners, according to a study in this month’s Biological Psychiatry. The findings point to the lateral prefrontal cortex’s role in emotion regulation, and suggest that improved function within this region may also improve day-to-day mood.

“What we found, as you might expect, was that everybody felt badly on the day of the conflict with their partners,” says lead author Christine Hooker, assistant professor of psychology in Harvard’s Faculty of Arts and Sciences. “But the day after, people who had high lateral prefrontal cortex activity felt better and the people who had low lateral prefrontal cortex activity continued to feel badly.”

Hooker’s co-authors are Ozlem Ayduk, Anett Gyurak, Sara Verosky, and Asako Miyakawa, all of the University of California at Berkeley.

Research has previously shown that the lateral prefrontal cortex is associated with emotion regulation in laboratory tests, but the effect has never been proven to be connected to experiences in day-to-day life.

This study involved healthy couples in a relationship for longer than three months. While in an fMRI scanner, participants viewed pictures of their partners with positive, negative, or neutral facial expressions and their neural activity was recorded while reacting to the images. While in the lab, participants were also tested for their broader cognitive control skills, such as their ability to control impulses and the shift and focus of attention.

For three weeks, the couples also recorded in an online diary their daily emotional state and whether they had had a fight with their partners.

Hooker found that participants who displayed greater activity in their lateral prefrontal cortex while viewing their partners’ negative facial expressions in the scanner were less likely to report a negative mood the day after a fight with their partners, indicating that they were better able to emotionally “bounce back” after the conflict.

She also found that those who had more activity in the lateral prefrontal cortex and greater emotional regulation after a fight displayed more cognitive control in laboratory tests, indicating a link between emotion regulation and broader cognitive control skills.

“The key factor is that the brain activity in the scanner predicted their experience in life,” says Hooker. “Scientists believe that what we are looking at in the scanner has relevance to daily life, but obviously we don’t live our lives in a scanner. If we can connect what we see in the scanner to somebody’s day-to-day emotion-regulation capacity, it could help psychologists predict how well people will respond to stressful events in their lives.”

WHAT: National Institutes of Health (NIH) scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the sponge-like brain deterioration typically seen in prion diseases. Instead, it resembles a form of human Alzheimer’s disease, cerebral amyloid angiopathy, that damages brain arteries.

The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID’s Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups: those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer’s disease, Dr. Chesebro says.

Psychosurgery is making a comeback. Recently published case series have shown encouraging results of so-called deep brain stimulation (DBS) in treatment-resistant obsessive-compulsive disorder, depressive disorders, and Tourette syndrome. In the current issue of Deutsches Ärzteblatt International, authors Jens Kuhn (University of Cologne) and Theo P J Gründer (Max Planck Institute, Cologne) and their co-authors provide an introduction to the method (Dtsch Arztebl Int 2010; 107(7)105-13).

In order to determine the clinical utility of DBS in psychiatric disorders, the authors evaluated therapeutic studies from 1980 to 2009. They found improvement rates of between 35% and 70% in treatment-resistant obsessive-compulsive disorder, depression, and Tourette syndrome. The rate of side effects associated with DBS was usually low and mostly reversible by modulating the stimulation parameters.

This favourable side effect profile is not all that surprising because DBS is a procedure that is well known; it has been in use for 20 years. In Parkinson’s disease and essential tremor, the method has proved to be so effective that it has been licensed as a therapeutic option for many years. To administer DBS, two electrodes are implanted into the patient that deliver continuous, high frequency, short electrical impulses, enabling modulation of the functional neuronal circuits. The electrodes are connected via a cable to an impulse generator, which is usually implanted below the collarbone.

Although DBS seems to offer new perspectives for the treatment of psychiatric disorders, further studies into its efficacy, mechanisms of action, and side effect profile and especially its long term course are needed.

UC Irvine neurobiologists are providing the first visual evidence that learning promotes brain health – and, therefore, that mental stimulation could limit the debilitating effects of aging on memory and the mind.

Using a novel visualization technique they devised to study memory, a research team led by Lulu Chen and Christine Gall found that everyday forms of learning animate neuron receptors that help keep brain cells functioning at optimum levels.

These receptors are activated by a protein called brain-derived neurotrophic factor, which facilitates the growth and differentiation of the connections, or synapses, responsible for communication among neurons. BDNF is key in the formation of memories.

“The findings confirm a critical relationship between learning and brain growth and point to ways we can amplify that relationship through possible future treatments,” says Chen, a graduate researcher in anatomy & neurobiology.

Study results appear in the early online edition of the Proceedings of the National Academy of Sciences for the week of March 1.

In addition to discovering that brain activity sets off BDNF signaling at the sites where neurons develop synapses, researchers determined that this process is linked to learning-related brain rhythms, called theta rhythms, vital to the encoding of new memories.

Theta rhythms occurring in the hippocampus involve numerous neurons firing synchronously at a rate of three to eight times per second. These rhythms have been associated with long-term potentiation, a cellular mechanism underlying learning and memory.

In rodent studies, the team found that both unsupervised learning and artificial application of theta rhythms triggered BDNF signaling at synapse creation sites.

“This relationship has implications for maintaining good brain health,” says Gall, a professor of anatomy & neurobiology. “There is evidence that theta rhythms weaken as we age, and our discoveries suggest that this can result in memory impairment. On the other hand, they suggest that staying mentally active as we age can keep neuronal BDNF signaling at a constant rate, which may limit memory and cognitive decline.”

Scientists are beginning to find out why people with Parkinson’s disease often feel socially awkward. Parkinson’s patients find it harder to recognize expressions of emotion in other people’s faces and voices, report two studies published by the American Psychological Association.

One of the studies raises questions about how deep brain stimulation, the best available treatment for patients who no longer respond to medication, more strongly affects the recognition of fear and sadness.

A neurodegenerative disorder, Parkinson’s causes tremors, stiffness and balance problems, as well as fairly frequent depression and dementia.

In the March issue of Neuropsychology, Heather Gray, PhD, and Linda Tickle-Degnen, PhD, report that people with Parkinson’s disease, compared with matched controls, often have difficulty discerning how others are feeling.

Their meta-analysis of 34 different studies using data from 1,295 participants shows a robust link between Parkinson’s and specific deficits in recognizing emotions, especially negative emotions, across different types of stimuli and tasks.

The meta-analysis, conducted at Harvard Medical School and Tufts University, found that patients typically had some degree of problem identifying emotion from faces and voices.

Further clarification is provided in a second study that showed that deep-brain stimulation, compared with medication, caused a consistently large deficit in the recognition of fear and sadness two key facial expressions that, when understood, aid survival. That study is published in the January issue of Neuropsychology.

Researchers led by Julie Péron, PhD, at the Centre Hospitalier Universitaire de Rennes in France, compared the ability of people with Parkinson’s in three different groups to recognize facial emotions: 24 advanced patients implanted with deep-brain stimulators after they didn’t respond or were sensitive to oral levodopa (the usual drug for the disease); 20 advanced patients given apomorphine hydrochloride by injection or infusion pump while they waited an implant; and 30 healthy controls.

Researchers tested all participants using standard photographs of facial expression before and three months after they were treated. Before implantation of the stimulators, all participants read facial expressions equally well.

Patients in the surgical group were implanted with stimulators, electrical devices that prod the brain’s subthalamic nucleus, a small, lens-shaped structure, to normalize the nerve signals that control movement. This nucleus is part of the basal ganglia system, which is thought to integrate movement, cognition and emotion.

Three months after treatment, only the patients with stimulators not the drug-treated patients or the healthy controls were significantly worse at recognizing fear and sadness. Patients with stimulators confused those expressions with others, such as surprise, or even no emotion. Medicated patients and healthy controls were either accurate about fear and sadness or occasionally mistook them for other negative emotions, such as disgust.

“Having Parkinson’s predisposes an individual to errors in emotion recognition,” said Gray. “The research in France, along with previous studies, indicates that deep-brain stimulation produces an even more severe deficit.”

Why would treating a movement disorder affect the perception of emotions? Implants affect a part of the brain that reaches across functions, so the authors suggested that the same electrical stimulation that calms over-excited motor activity may also somehow inhibit emotional processing.

Although the impact of Parkinson’s and deep-brain stimulation varies by patient, it’s important to understand. “The first step is to educate patients and their close associates about the potential for emotion recognition difficulties, so they can learn to manage some of the social consequences, such as misunderstanding and frustration,” said Gray and Tickle-Degnen. The next step might be training in emotion recognition, which they said has shown promise.

The next advance in treating major depression may relate to a group of brain chemicals that are involved in virtually all our brain activity, according to a study published in Biological Psychiatry. The study is co-authored by Drs. Andrea J. Levinson and Zafiris J. Daskalakis of the Centre for Addiction and Mental Health (CAMH).

This study shows that compared to healthy individuals, people who have major depressive disorder have altered functions of the neurotransmitter GABA (gamma-aminobutyric acid). In the study, individuals with the most treatment-resistant forms of illness demonstrated the greatest reductions of GABA levels in the brain.

This points to the possibility that medications which correct a GABA imbalance could advance the treatment of major depressive disorder. Approximately 4% of Canadians experience major depressive disorder each year.

Several current medications for mood disorders correct imbalances in neurotransmitters such as serotonin and dopamine. However, many patients do not benefit from these medications. “Our findings build on the idea that some current medications do not help many patients because those drugs don’t affect the GABA-related brain chemistry,” says study author Dr. Andrea Levinson.

Applying the brakes

The GABA neurotransmitter and its receptors are involved in many different brain functions. Imbalances in GABA also are relevant to bipolar disorder, schizophrenia, and anxiety disorder.

The GABA neurotransmitter and its receptors are critical to how humans think and act, Dr. Levinson adds. “We apply so many conscious and unconscious perceptions and judgments to our actions at every second, without even realizing that we are doing so,” she says. “GABA is part of the brain system that allows us to fine-tune our moods, thoughts, and actions with an incredible level of detail.”

“It’s a little like driving a car. You need the accelerator, but at every stage you need the brakes to work. Some of our neurotransmitters apply the spark and the gas to the engine, and GABA supplies the brakes,” she says. “GABA provides the necessary inhibitory effect that we need in order to block out excessive brain activity that in depression may lead to excessive negative thinking.”

In addition, this study points to the reason why electroconvulsive therapy is still the most efficacious therapy for major depressive disorder, Dr. Levinson adds. “Electroconvulsive therapy may act on GABA brain chemicals in a way that can reset the balance,” she says.

Largest study to date

This study of 85 people is the largest such research effort on GABA and major depressive disorder to date. It compared four groups: 25 individuals with treatment-resistant depression, 16 with major depression who were unmedicated, 19 individuals with major depression who were successfully treated with medication and had normal mood, and a control group of 25 healthy individuals.

In all groups, a thumb twitch response to transcranial magnetic (brain) stimulation (TMS) was used to measure how GABA acts physiologically in the brain. GABA receptors were found to be dysfunctional in the three groups with major depressive disorder when compared to healthy subjects. In people who were the least responsive (treatment-resistant) to medications, the physiological effect of GABA in the brain was at its lowest.

Personalized medicine

“We are advancing the goal of a truly personalized medicine,” says study co-author Dr. Daskalakis. “It is intriguing to think that we may soon be able to apply simple brain stimulation to identify which treatments are most likely to help the individual person, eliminating the guesswork. That is, through these findings we may be able to one day determine who is and who is not going to respond to traditional pharmacological approaches to depression.”