Bad experiences enhance memory formation about places, scientists at The University of Queensland have found.

Dr Oliver Baumann from the Queensland Brain Institute found that associating negative imagery with specific locations activates a part of the brain responsible for forming memory of places during navigation – the parahippocampal cortex.

“This heightened recall occurs automatically, without people even being aware that the negative imagery is affecting their memories,” said Dr Baumann, who worked on the study in the QBI’s Mattingley lab.

“It could serve as a cue for avoiding potential threats,” Dr Baumann said.

“Our findings show that emotions can exert a powerful influence on spatial and navigational memory for places.

“In future we might be able to boost memory functions by triggering the positive side-effects of emotional arousal, while avoiding the need for negative experiences.”

For the research, Professor Jason Mattingley built a “virtual house” and staged events in each room unrelated to the subject navigating the house.

The events were designed to elicit an emotional response – positive, negative, or neutral, and varied in their rate of occurrence.

“The events were illustrated using images from the International Affective Picture System library and included dramatic scenes of attack and threat, as well as more pleasant imagery,” Dr Baumann said.

The day after navigating through the house, participants viewed static images of the house without the emotional imagery, while their neural activity was recorded using an MRI scanner.

“The results showed that emotional arousal exerted a powerful influence on memory by enhancing parahippocampal activity,” Dr Baumann said.

The study was published in the Journal of Cognitive Neuroscience.

(Source: uq.edu.au)

Several studies have shown that expecting a reward or punishment can affect brain activity in areas responsible for processing different senses, including sight or touch. For example, research shows that these brain regions light up on brain scans when humans are expecting a treat. However, researchers know less about what happens when the reward is actually received—or an expected reward is denied. Insight on these scenarios can help researchers better understand how we learn in general.

To get a better grasp on how the brain behaves when people who are expecting a reward actually receive it, or conversely, are denied it, Tina Weis of Carl-von-Ossietzky University and her colleagues monitored the auditory cortex—the part of the brain that processes and interprets sounds—while volunteers solved a task in which they had a chance of winning 50 Euro cents with each round, signaled by a specific sound. Their findings show that the auditory cortex activity picked up both when participants were expecting a reward and received it, as well as when their expectation of receiving no reward was correct.

The article is entitled “Feedback that Confirms Reward Expectation Triggers Auditory Cortex Activity.” It appears in the Articles in Press section of the Journal of Neurophysiology, published by the American Physiological Society.

Methodology

The researchers worked with 105 healthy adult volunteers with normal hearing. While each volunteer received a functional MRI (fMRI)—a brain scan that measures brain activity during tasks—the researchers had them solve a task with sounds where they had the chance of winning money at the end of each round. At the beginning of a round participants heard a sound and had to learn if this sound signified that they could win a 50 Euro cents reward or not. They then saw a number on a screen and had to press a button to indicate whether the number was greater or smaller than 5. If the sound before indicated that they could receive a reward and they solved the number task quickly and correctly, an image of a 50 Euro cents coin appeared on the screen. The researchers monitored brain activity in the subjects’ auditory cortex throughout the task, paying special attention to what happened when they received the reward, or not, at the end of the round.

Results

The study authors found that when the volunteers were expecting and finally received a reward, then their auditory cortex was activated. Similarly, there was an increase in brain activity in this area when the subjects weren’t expecting a reward and didn’t get one. There was no additional activity when they were expecting a reward and didn’t get one.

Importance of the Findings

These findings add to accumulating evidence that the auditory cortex performs a role beyond just processing sound. Rather, this area of the brain appears to be activated during other activities that require learning and thought, such as confirming expectations of receiving a reward.

"Our findings thus support the view of a highly cognitive role of the auditory cortex," the study authors say.

(Source: eurekalert.org)

New research that looked at whether two commonly prescribed statin medicines, used to lower low-density lipoprotein (LDL) or‘bad cholesterol’ levels in the blood, can adversely affect cognitive function has found that one of the drugs tested caused memory impairment in rats. 

Between six and seven million people in the UK take statins daily and the findings follow anecdotal evidence of people reporting that they feel that their newly prescribed statin is affecting their memory.  Last year, the US Food and Drug Administration (FDA) insisted that all manufacturers list in their side effects that statins might affect cognitive function. 

The study, led by scientists at the University of Bristol and published in the journal PLOS ONE, tested pravastatin and atorvostatin (two commonly prescribed statins) in rat learning and memory models. The findings show that while no adverse cognitive effects were observed in rat performance for simple learning and memory tasks for atorvostatin, pravastatin impaired their performance.

Rats were treated daily with pravastatin (brand name - Pravachol) or atorvostatin (brand name - Lipitor) for 18 days. The rodents were tested in a simple learning task before, during and after treatment, where they had to learn where to find a food reward. On the last day of treatment and following one week withdrawal, the rats were also tested in a task which measures their ability to recognise a previously encountered object (recognition memory).

The study’s findings showed that pravastatin tended to impair learning over the last few days of treatment although this effect was fully reversed once treatment ceased. However, in the novel object discrimination task, pravastatin impaired object recognition memory.  While no effects were observed for atorvostatin in either task.

The results suggest that chronic treatment with pravastatin impairs working and recognition memory in rodents. The reversibility of the effects on stopping treatment is similar to what has been observed in patients, but the lack of effect of atorvostatin suggests that some types of statin may be more likely to cause cognitive impairment than others. 

Neil Marrion, Professor of Neuroscience at Bristol’s School of Physiology and Pharmacology in the Faculty of Medical and Veterinary Sciences and the study’s lead author, said: “This finding is novel and likely reflects both the anecdotal reports and FDA advice.  What is most interesting is that it is not a feature of all statins. However, in order to better understand the relationship between statin treatment and cognitive function, further studies are needed.”

(Source: bris.ac.uk)

Greg Noack was 24 when he moved from Ontario to Victoria, B.C. He had just graduated from college and was looking forward to a fresh start.

One early morning in 1996, as he was returning home from his graveyard shift at the hotel, Noack was attacked from behind by a group of men.

He doesn’t remember being struck on the head. He does remember waking from a 15-day coma to learn he had suffered a traumatic brain injury (TBI).

Noack, through the care of his health-care team, relearned how to walk, write, and feel particular emotions.

“I was enamoured by what my therapists were able to do for me,” said Noack. “I was lucky that I got back most of my function.”

Three years post-injury, Noack enrolled in Sault College’s Occupational Therapist Assistant/Physical Therapist Assistant Program and graduated with honours.

Shortly after, Noack was hired by the Toronto Rehab Acquired Brain Injury Rehab team as an occupational therapist assistant and later became a rehab therapist.

Most recently, he was seconded to Dr. Robin Green’s traumatic brain injury research team.

Dr. Green, Senior Scientist and Neuropsychologist, Toronto Rehab and Canada Research Chair in Traumatic Brain Injury, and her Toronto Rehab team have been studying impediments to brain injury recovery as well as treatments to offset the impediments.

Dr. Green’s work suggests that moderate-severe TBI may be a progressive neurological disorder –a whole new way of perceiving the condition.

“What may be occurring after a serious brain injury,” said Dr. Green, “is that damaged tissue is leaving healthy areas of the brain disconnected and under stimulated. Over time, healthy areas may deteriorate.”

Importantly, they discovered that in people with chronic moderate-severe TBI,  environmental enrichment – increased physical, social and cognitive stimulation - can offset this deterioration.

Her research paper, entitled “Environmental enrichment may protect against hippocampal atrophy in the chronic stages of traumatic brain injury,” was published September 24 in Frontiers in Human Neuroscience.

In their study of 25 patients with moderate-severe TBI, her team found a positive reaction to environmental enrichment.

Those who reported greater amounts of environmental enrichment – for example, reading, problem solving exercises, puzzles, physical activity, socializing – at 5 months after their injury showed less shrinkage of the hippocampus (associated with memory functioning) from 5 to 28 months post-injury.

“People with moderate-severe TBI are commonly unable to return to the same level of engagement in their work, school or social lives as before the injury,” said Dr. Green. “However, those with greater environmental enrichment may be keeping vulnerable areas stimulated. Environmental enrichment is also known to increase production of neurons in the hippocampus and to promote their integration into existing brain networks.”

Based on the findings from their study, Green’s team is now engaged in research designed to proactively offset deterioration, which includes the delivery of environmental enrichment to patients. Noack is instrumental in delivering enriched therapy for TBI patients who are enrolled in one of Dr. Green’s research studies.

“One thing I loved about this study is that it facilitated greater customization of a patient’s care,” said Noack. “I could see how my patients benefited from the increased amount of stimulation through extended therapy.”

“Although the brains of patients are showing negative changes, patients are still showing recovery of their functioning in spite of it,” said Dr. Green. “If we are able to offset the negative brain changes through the treatments we are developing, we may be able to very significantly improve patients’ recovery and the quality of their aging with a brain injury.”

(Source: uhn.ca)

Researchers from Penn Medicine and University of Oviedo Identify Molecular Pathway Linking ICU Ventilation to Brain Damage

At least 30 percent of patients in intensive care units (ICUs) suffer some form of mental dysfunction as reflected in anxiety, depression, and especially delirium. In mechanically-ventilated ICU patients, the incidence of delirium is particularly high, about 80 percent, and may be due in part to damage in the hippocampus, though how ventilation is increasing the risk of damage and mental impairment has remained elusive.

Now, a new study published in the American Journal of Respiratory and Critical Care Medicine fromresearchers at the University of Oviedo in Spain, St. Michael’s Hospital in Toronto, Canada, and the Perelman School of Medicine at the University Pennsylvaniafound a molecular mechanism that may explain the connection between mechanical ventilation and hippocampal damage in ICU patients. 

The investigators, including Adrian González-López, PhD, in the laboratory of Guillermo M. Albaiceta, MD, PhD at the University of Oviedo , and co-authored by Konrad Talbot, PhD, an assistant research professor in Neurobiology in the Department of Psychiatry at Penn Medicine, began by studying the hippocampus in control mice and in mice on low or high-pressure mechanical ventilation for 90 minutes. Compared to the controls, those on either low- or high-pressure ventilation showed evidence of neuronal cell death in the hippocampus, as a result of a cell suicide program called apoptosis.

Searching for the molecular cause of the ventilation-induced apoptosis, the team discovered that a well-known apoptosis trigger had been set off in the hippocampus of the ventilated animals. That trigger is dopamine-induced suppression of a molecule known as Akt, which normally acts to prevent neuronal apoptosis. Akt suppression was clearly evident in the hippocampus of the ventilated mice and was associated with a hyperdopaminergic state (increased levels of dopamine) in that brain area. The ventilated mice had elevated gene expression of the enzyme tyrosine hydroxylase, which is critical in synthesizing dopamine. The resulting rise in dopamine increases the strength of dopamine receptor activation in the hippocampus.

The investigators hypothesized that ventilation-induced apoptosis in the hippocampus was at least partly mediated by elevated activation of dopamine receptors in that brain area. This was confirmed by showing that pretreatment of mice with type 2 (D2) dopamine receptor blockers injected into the ventricles of the brain significantly reduced ventilation-induced apoptosis in the hippocampus.

How mechanical ventilation manages to affect the hippocampus was answered by experiments on mice in which the vagus cranial nerve connecting the lungs with the brain was severed. In these mice, mechanical ventilation had virtually no effect on levels of the dopamine-synthesizing enzyme or on apoptosis in the hippocampus. 

The investigators then studied the consequences of ventilation and elevated hippocampal dopamine on dysbindin-1, a protein known to affect levels of cell surface D2 dopamine receptors, cognition, and possibly the risk of psychosis. High-pressure ventilation in mice caused an increase in gene expression of dysbindin-1C, and later, in protein levels of dysbindin-1C. Dopamine alone had similar effects on dysbindin-1C in hippocampal slice preparations, effects that were inhibited by D2 receptor blockers.

Since dysbindin-1 can lower cell-surface D2 receptors and protect against apoptosis, the authors speculate that increased dysbindin-1C expression in the ventilated mice may reflect compensatory responses to ventilation-induced hippocampal apoptosis. That possibility applies to ICU cases given the additional finding by the authors that total dysbindin-1 was increased in hippocampal neurons of ventilated compared to non-ventilated humans who died in the ICU.

The findings could lead to new therapeutic uses of established drugs and targets for new drugs that activate a molecular pathway mediating adverse effects of ICU ventilation on brain function.

“The results prove the existence of a pathogenic mechanism of lung stretch-induced hippocampal apoptosis that could explain the development of neurobehavioral disorders in patients exposed to mechanical ventilation,” the authors write.  One of the coauthors, Dr. Talbot, adds: “The study indicates the need to reevaluate use of D2 receptor antagonists in minimizing the negative cognitive effects of mechanical ventilation in ICU patients and to evaluate the novel possibility that elevation in dysbindin-1C expression can also reduce those effects.”

The corresponding author, Dr. Albaiceta, offered a look at future research on this topic: “Now that we have established the mouse model, we are mainly looking for therapeutic approaches aimed at avoiding the vagal activation caused by mechanical ventilation and therefore prevent the deleterious effects observed in the hippocampus,” he said. “We are also interested in studying the relationship between the different described gene polymorphisms of dysbindin, Akt, and type 2 dopamine receptor versus the incidence of neurological disorders in patients on ventilation in ICUs. This could help us to identify susceptible individuals to in which a preventive treatment could be effective.”

(Source: uphs.upenn.edu)

For years, scientists have attempted to understand how Alzheimer’s disease harms the brain before memory loss and dementia are clinically detectable. Most researchers think this preclinical stage, which can last a decade or more before symptoms appear, is the critical phase when the disease might be controlled or stopped, possibly preventing the failure of memory and thinking abilities in the first place.

Important progress in this effort is reported in October in Lancet Neurology. Scientists at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University School of Medicine in St. Louis, working in collaboration with investigators at the University of Maastricht in the Netherlands, helped to validate a proposed new system for identifying and classifying individuals with preclinical Alzheimer’s disease.

Their findings indicate that preclinical Alzheimer’s disease can be detected during a person’s life, is common in cognitively normal elderly people and is associated with future mental decline and mortality. According to the scientists, this suggests that preclinical Alzheimer’s disease could be an important target for therapeutic intervention.

A panel of Alzheimer’s experts, convened by the National Institute on Aging in association with the Alzheimer’s Association, proposed the classification system two years ago. It is based on earlier efforts to define and track biomarker changes during preclinical disease.

According to the Washington University researchers, the new findings offer reason for encouragement, showing, for example, that the system can help predict which cognitively normal individuals will develop symptoms of Alzheimer’s and how rapidly their brain function will decline. But they also highlight additional questions that must be answered before the classification system can be adapted for use in clinical care.

“For new treatments, knowing where individuals are on the path to Alzheimer’s dementia will help us improve the design and assessment of clinical trials,” said senior author Anne Fagan, PhD, research professor of neurology. “There are many steps left before we can apply this system in the clinic, including standardizing how we gather and assess data in individuals, and determining which of our indicators of preclinical disease are the most accurate. But the research data are compelling and very encouraging.”

The classification system divides preclinical Alzheimer’s into three stages:

• Stage 1: Levels of amyloid beta, a protein fragment produced by the brain, begin to fall in the spinal fluid. This indicates that the substance is beginning to form plaques in the brain.

• Stage 2: Levels of tau protein start to rise in the spinal fluid, indicating that brain cells are beginning to die. Amyloid beta levels are still abnormal and may continue to fall.

• Stage 3: In the presence of abnormal amyloid and tau biomarker levels, subtle cognitive changes can be detected by neuropsychological testing. By themselves, these changes cannot establish a clinical diagnosis of dementia.

The researchers applied these criteria to research participants studied from 1998 through 2011 at the Knight Alzheimer Disease Research Center. The center annually collects extensive cognitive, biomarker and other health data on normal and cognitively impaired volunteers for use in Alzheimer’s studies.

The scientists analyzed information on 311 individuals age 65 or older who were cognitively normal when first evaluated. Each participant was evaluated annually at the center at least twice; the participant in this study with the most data had been followed for 15 years.

At the initial testing, 41 percent of the participants had no indicators of Alzheimer’s disease (stage 0); 15 percent were in stage 1 of preclinical disease; 12 percent were in stage 2; and 4 percent were in stage 3. The remaining participants were classified as having cognitive impairments caused by conditions other than Alzheimer’s (23 percent) or did not meet any of the proposed criteria (5 percent).

“A total of 31 percent of our participants had preclinical disease,” said Fagan. “This percentage matches findings from autopsy studies of the brains of older individuals, which have shown that about 30 percent of people who were cognitively normal had preclinical Alzheimer’s pathology in their brain.”

Scientists believe the rate of cognitive decline increases as people move through the stages of preclinical Alzheimer’s. The new data support this idea. Five years after their initial evaluation, 11 percent of the stage 1 group, 26 percent of the stage 2 group, and 52 percent of the stage 3 group had been diagnosed with symptomatic Alzheimer’s.

Individuals with preclinical Alzheimer’s disease were six times more likely to die over the next decade than older adults without preclinical Alzheimer’s disease, but researchers don’t know why.

“Risk factors for Alzheimer’s disease might also be associated with other life-threatening illnesses,” Fagan said. “It’s also possible that the presence of Alzheimer’s hampers the diagnosis and treatment of other conditions or contributes to health problems elsewhere in the body. We don’t have enough data yet to say, but it’s an issue we’re continuing to investigate.”

(Source: news.wustl.edu)