Posts tagged science
Articles and news from the latest research reports.
The flexible tail of the prion protein poisons brain cells
For decades, there has been no answer to the question of why the altered prion protein is poisonous to brain cells. Neuropathologists from the University of Zurich and University Hospital Zurich have now shown that it is the flexible tail of the prion protein that triggers cell death. These findings have far-reaching consequences: only those antibodies that target the tail of the prion protein are suitable as potential drugs for combating prion diseases.
Prion proteins are the infectious pathogens that cause Mad Cow Disease and Creutzfeldt-Jakob disease. They occur when a normal prion protein becomes deformed and clumped. The naturally occurring prion protein is harmless and can be found in most organisms. In humans, it is found in our brain cell membrane. By contrast, the abnormally deformed prion protein is poisonous for the brain cells. Adriano Aguzzi, Professor of Neuropathology at the University of Zurich and University Hospital Zurich, has spent many years exploring why this deformation is poisonous. Aguzzi’s team has now discovered that the prion protein has a kind of «switch» that controls its toxicity. This switch covers a tiny area on the surface of the protein. If another molecule, for example an antibody, touches this switch, a lethal mechanism is triggered that can lead to very fast cell death.
Flexible tail induces cell death
In the current edition of «Nature», the scientists demonstrate that the prion protein molecule comprises two functionally distinct parts: a globular domain, which is tethered to the cell membrane, and a long and unstructured tail. Under normal conditions, this tail is very important in order to maintain the functioning of nerve cells. By contrast, in the case of a prion infection the pathogenic prion protein interacts with the globular part and the tail causes cell death – this is the hypothesis put forward by the researchers.
Aguzzi and his team tested this by generating mimetic antibodies in tissue sections from the cerebellum of mice which have a similar toxicity to that of a prion infection. The researchers found that these antibodies tripped the switch of the prion protein. «Prion proteins with a trimmed version of the flexible tail can, however, no longer damage the brain cells, even if their switch has been recognized by antibodies», explains Adriano Aguzzi. «This flexible tail is responsible for causing cell death.» If the tail is bound and made inaccessible using a further antibody, activation of the switch can likewise no longer trigger cell death.
«Our discovery has far-reaching consequences for understanding prion diseases», says Aguzzi. The findings reveal that only those antibodies that target the prion protein tail are suitable for use as potential drugs. By contrast, antibodies that trip the switch of the prion are very harmful and dangerous.
By tracking maggots’ food choices, scientists open significant new window into human learning
The squirming larva of the humble fruit fly, which shares a surprising amount of genetic material with the human being, is helping scientists to understand the way we learn information from one another.
Fruit flies have long served as models for studying behaviour because their cognitive mechanisms are parallel to humans’, but much simpler to study.
Fruit flies exhibit many of the same basic behaviours as humans and share 87 per cent of the material that is responsible for genetically based neurological disorders, making them a potent model for study.
While adult fruit flies have been studied for decades, the new paper reveals that their larvae, which are even simpler organisms, may be more valuable models for behavioral research. A fruit fly larva has only 3,000 neurons, for example, while a human has about 10 billion.
The McMaster researchers were able to prove that the larvae, or maggots, are capable of social learning, which opens the door to many other experiments that could provide valuable insights into human behaviour, end even lead to treatments for human disorders, the scientists say.
“People have been studying adult flies for decades now,” explains the study’s lead author, Zachary Durisko. “The larval stage is much simpler in terms of the brain, but behaviour at the larval stage has been less well studied. Here we have a complex behaviour in this even simpler model.”
Durisko and Reuven Dukas, both of McMaster’s Department of Psychology, Neuroscience and Behaviour, have shown that fruit fly larvae are able to distinguish which food sources have been used by other larvae and utilize the information to benefit themselves by choosing to eat from those same established sources instead of available alternatives.
The maggots’ attraction to food that others have been eating is based on smell, and is roughly equivalent to a person arriving in a new city, seeing two restaurants and choosing a busy one over an empty one, the researchers explain.
“They prefer the social over the non-social like we would do, and they learn to prefer the social over the non-social,” Dukas says.
In fact, the motivations may be similar in each case, and could include accepting the judgment of others as an indication of quality and seeking the company of others for protection from harm.
Durisko, the lead author, recently completed his PhD at McMaster, and Dukas, his co-author, is a professor at the university. Their work is published in the prestigious Proceedings of the Royal Society B, one of the society’s biological journals.
The researchers used several combinations of foods, both completely fresh and previously used, and of varying degrees of nutritional value, to compare the maggots’ preferences.
Second known case of patient developing synesthesia after brain injury
About nine months after suffering a stroke, the patient noticed that words written in a certain shade of blue evoked a strong feeling of disgust. Yellow was only slightly better. Raspberries, which he never used to eat very often, now tasted like blue – and blue tasted like raspberries.
High-pitched brass instruments—specifically the brass theme from James Bond movies—elicited feelings of ecstasy and light blue flashes in his peripheral vision and caused large parts of his brain to light up on an MRI. Music played by a euphonium, a tenor-pitched brass instrument, shut down those sensations.
The patient said he was initially frightened by the mixed messages his brain was sending him and the conflicting senses he was experiencing. He was so worried that something was seriously wrong with him that he raised it with a nurse only as he was leaving an appointment at St. Michael’s Hospital in downtown Toronto.
Physicians and researchers immediately recognized he had synesthesia, a neurological condition in which people experience more than one sense at the same time. They may “see” words or numbers as colours, hear sounds in response to smells or feel something in response to sight.
Most synesthetes are born with the condition, and include some of the world’s most famous authors and artists, including author Vladimir Nabakov, composer Franz Liszt, painter Vasily Kandinsky and singer-songwriter Billy Joel.
The Toronto patient is only the second known person to have acquired synesthesia as a result of a brain injury, in this case a stroke. His case was described in the August issue of the journal Neurology by Dr. Tom Schweizer, a neuroscientist and director of the Neuroscience Research Program at St. Michael’s Li Ka Shing Knowledge Institute.
Dr. Schweizer examined the patient’s brain activity in a functional MRI and compared it to six men of similar age (45) and education (18 years) as each listened to the James Bond Theme and a euphonium solo.
When the James Bond Theme was played, large areas of the patient’s brain lit up including the thalamus (the brain’s information switchboard), the hippocampus (which deals with memory and spatial navigation) and the auditory cortex (which processes sound).
"The areas of the brain that lit up when he heard the James Bond Theme are completely different from the areas we would expect to see light up when people listen to music," Dr. Schweizer said. "Huge areas on both sides of the brain were activated that were not activated when he listened to other music or other auditory stimuli and were not activated in the control group."
The patient and members of the control group also viewed 10-second blocks of words presented in black (which elicits no emotional response in the patient), yellow (mild disgust response) and blue (intense disgust response).
Reading blue letters produced extensive activity in the parts of the patient’s brain responsible for sensory information and processing emotional stimuli and similar but less intense responses for yellow letters. Control groups showed no heightened brain activity in response to the different coloured letters.
Dr. Schweizer said the fact that the patient had very targeted and specific responses to certain stimuli – and that these responses were not experienced by the control group – suggests that his synesthesia was caused as his brain tried to repair itself after his stroke and got cross-wired.
The patient’s stroke occurred in the thalamus, the brain’s central relay station. That’s the same part of the brain affected by the only other reported case of acquired synesthesia.
(Source: eurekalert.org)
Cockatoos know what is going on behind barriers
How do you know that the cookies are still there although they have been placed out of your sight into the drawer? How do you know when and where a car that has driven into a tunnel will reappear? The ability to represent and to track the trajectory of objects, which are temporally out of sight, is highly important in many aspects but is also cognitively demanding. Alice Auersperg and her team from the University of Vienna and Oxford show that “object permanence” abilities in a cockatoo levels apes and four year old human toddlers. The researchers published their findings in the journal “Journal of Comparative Psychology”.
For investigating spatial memory and tracking in animals and human infants a number of setups have been habitually used. These can roughly be subdivided depending on what is being moved: a desired object (food reward), the hiding places for this object or the test animal itself: In the original invisible displacement tasks, designed by French psychologist Jean Piaget in the 50s, the reward is moved underneath a small cup behind one or more bigger screens and its contents is shown in between visits: if the cup is empty we know that the reward must be behind the last screen visited. Humans solve this task after about two years of age, whereas in primates only the great apes show convincing results.
Likely to be even more challenging in terms of attention, are “Transposition” tasks: the reward is hidden underneath one of several equal cups, which are interchanged one or more times. Human children struggle with this task type more than with the previous and do not solve it reliably before the age of three to four years whereas adult apes solve it but have more trouble with double than single swaps.
In “Rotation” tasks several equal cups, one bearing a reward are aligned in parallel on a rotatable platform, which is rotated at different angles. “Translocation” tasks are similar except that the cups are not rotated but the test animal is carried around the arrangement and released at different angles to the cup alignment. Children find Translocation tasks easier than Rotation tasks and solve them at two to three years of age.
A team of international Scientists tested eight Goffin cockatoos (Cacatua goffini), a conspicuously inquisitive and playful species on visible as well as invisible Piagetian object displacements and derivations of spatial transposition, rotation and translocation tasks. Birgit Szabo, one of the experimenters from the University of Vienna, says: “The majority of our eight birds readily and spontaneously solved Transposition, Rotation and Translocation tasks whereas only two out of eight choose immediately and reliably the correct location in the original Piagetian invisible displacement task in which a smaller cup is visiting two of three bigger screens”. Alice Auersperg, the manager of the Goffin Lab who was also one of the experimenters, explains: “Interestingly and just opposite to human toddlers our cockatoos had more problems solving the Piagetian invisible displacements than the transposition task with which children struggle until the age of four. Transpositions are highly demanding in terms of attention since two occluding objects are moved simultaneously. Nevertheless, in contrast to apes, which find single swaps easier than double the cockatoos perform equally in both conditions”.
Similarly, Goffins had little complications with Rotations and Translocation tasks and some of them solved them at four different angles. Again, in contrast to children, which find Translocations easier than Rotations, the cockatoos showed no significant differences between the two tasks. Auguste von Bayern from the University of Oxford adds: ” We assume that the ability to fly and prey upon or being preyed upon from the air is likely to require pronounced spatial rotation abilities and may be a candidate trait influencing the animals’ performance in rotation and translocation tasks”.
Thomas Bugnayer from the University of Vienna concludes: “Finding that Goffins solve transposition, rotation and translocation tasks, which are likely to pose a large cognitive load on working memory, was surprising and calls for more comparative data in order to better understand the relevance of such accurate tracking abilities in terms of ecology and sociality”.
Increased fluctuation in blood pressure linked to impaired cognitive function in older people
Higher variability in visit-to-visit blood pressure readings, independent of average blood pressure, could be related to impaired cognitive function in old age in those already at high risk of cardiovascular disease, suggests a paper published today on BMJ.
There is increasing evidence that vascular factors contribute in development and progression of dementia. This is of special interest as cardiovascular factors may be amendable and thus potential targets to reduce cognitive decline and the incidence of dementia. Visit-to-visit blood pressure variability has been linked to cerebrovascular damage (relating to the brain and its blood vessels). It has also been shown that this variability can increase the risk of stroke.
It has been suggested that higher blood pressure variability might potentially lead to cognitive impairment through changes in the brain structures.
Researchers from the Leiden University Medical Center (Netherlands), University College Cork (Ireland) and the Glasgow University (UK) therefore investigated the association of visit-to-visit blood pressure variability (independent of average blood pressure) with cognitive function in older subjects at high risk of cardiovascular disease.
All data were obtained from the PROSPER study, which investigated the effect of statins in prevention of vascular events in older men and women. This study took data on 5,461 individuals aged 70-82 years old in Ireland, Scotland and the Netherlands. Average follow-up was three years.
Both systolic (peak pressure) and diastolic (minimum pressure) blood pressures were measured every three months in the same clinical setting. The variability between these measurements were calculated and used in the analyses.
The study used data on cognitive function where the following was tested: selective attention and reaction time; general cognitive speed; immediate and delayed memory performance.
Results showed that visit-to-visit blood pressure variability was associated with worse performance on all cognitive tests. The results were consistent after adjusting for cardiovascular disease and other risk factors.
The main findings of the study were: higher visit-to-visit blood pressure variability is associated with worse performance in different cognitive tests; higher variability is associated with higher risk of stroke and both these associations are independent of various cardiovascular risk factors, in particular, average blood pressure.
Researcher Simon Mooijaart, (Leiden University Medical Centre, Leiden, the Netherlands) says that by using a population of “over five thousand participants and over three years of blood pressure measurements, we showed that high visit-to-visit systolic and diastolic blood pressure variability associates with worse performance in different domains of cognitive function including selection attention, processing speed, immediate verbal memory and delayed verbal memory”. The researchers do add though that it is still unclear whether higher blood pressure variability is a cause or consequence of impaired cognitive function.
They suggest several explanations for their findings: firstly that blood pressure variability and cognitive impairment could stem from a common cause, with cardiovascular risk factors being the most likely candidate; secondly that variability might reflect a long term instability in the regulation of blood pressure and blood flow to the key organs in the body; thirdly that exaggerated fluctuations in blood pressure could result in the brain not receiving enough blood, which can cause brain injury, leading to impairment of cognitive function.
The researchers conclude that “higher visit-to-visit blood pressure variability independent of average blood pressure might be a potential risk factor with worse cognitive performance in older subjects at high risk of cardiovascular disease”. Given that dementia is a major public health issue, they say that further interventional studies are warranted to establish whether reducing blood pressure variability can decrease the risk of cognitive impairment in old age.
(Source: eurekalert.org)
Exercise May be the Best Medicine for Alzheimer’s
New research out of the University of Maryland School of Public Health shows that exercise may improve cognitive function in those at risk for Alzheimer’s by improving the efficiency of brain activity associated with memory. Memory loss leading to Alzheimer’s disease is one of the greatest fears among older Americans. While some memory loss is normal and to be expected as we age, a diagnosis of mild cognitive impairment, or MCI, signals more substantial memory loss and a greater risk for Alzheimer’s, for which there currently is no cure.
The study, led by Dr. J. Carson Smith, assistant professor in the Department of Kinesiology, provides new hope for those diagnosed with MCI. It is the first to show that an exercise intervention with older adults with mild cognitive impairment (average age 78) improved not only memory recall, but also brain function, as measured by functional neuroimaging (via fMRI). The findings are published in the Journal of Alzheimer’s Disease.
“We found that after 12 weeks of being on a moderate exercise program, study participants improved their neural efficiency – basically they were using fewer neural resources to perform the same memory task,” says Dr. Smith. “No study has shown that a drug can do what we showed is possible with exercise.”
Recommended Daily Activity: Good for the Body, Good for the Brain
Two groups of physically inactive older adults (ranging from 60-88 years old) were put on a 12-week exercise program that focused on regular treadmill walking and was guided by a personal trainer. Both groups – one which included adults with MCI and the other with healthy brain function – improved their cardiovascular fitness by about ten percent at the end of the intervention. More notably, both groups also improved their memory performance and showed enhanced neural efficiency while engaged in memory retrieval tasks.
The good news is that these results were achieved with a dose of exercise consistent with the physical activity recommendations for older adults. These guidelines urge moderate intensity exercise (activity that increases your heart rate and makes you sweat, but isn’t so strenuous that you can’t hold a conversation while doing it) on most days for a weekly total of 150 minutes.
Measuring Exercise’s Impact on Brain Health and Memory
One of the first observable symptoms of Alzheimer’s disease is the inability to remember familiar names. Smith and colleagues had study participants identify famous names and measured their brain activation while engaged in correctly recognizing a name – e.g., Frank Sinatra, or other celebrities well known to adults born in the 1930s and 40s. “The task gives us the ability to see what is going on in the brain when there is a correct memory performance,” Smith explains.
Tests and imaging were performed both before and after the 12-week exercise intervention. Brain scans taken after the exercise intervention showed a significant decrease in the intensity of brain activation in eleven brain regions while participants correctly identified famous names. The brain regions with improved efficiency corresponded to those involved in the pathology of Alzheimer’s disease, including the precuneus region, the temporal lobe, and the parahippocampal gyrus.
The exercise intervention was also effective in improving word recall via a “list learning task,” i.e., when people were read a list of 15 words and asked to remember and repeat as many words as possible on five consecutive attempts, and again after a distraction of being given another list of words.
“People with MCI are on a very sharp decline in their memory function, so being able to improve their recall is a very big step in the right direction,” Smith states.
The results of Smith’s study suggest that exercise may reduce the need for over-activation of the brain to correctly remember something. That is encouraging news for those who are looking for something they can do to help preserve brain function.
Dr. Smith has plans for a larger study that would include more participants, including those who are healthy but have a genetic risk for Alzheimer’s, and follow them for a longer time period with exercise in comparison to other types of treatments. He and his team hope to learn more about the impact of exercise on brain function and whether it could delay the onset or progression of Alzheimer’s disease.
Study finds evidence of nerve damage in around half of fibromyalgia patients
Small study could lead to identification of treatable diseases for some with chronic pain syndrome
About half of a small group of patients with fibromyalgia – a common syndrome that causes chronic pain and other symptoms – was found to have damage to nerve fibers in their skin and other evidence of a disease called small-fiber polyneuropathy (SFPN). Unlike fibromyalgia, which has had no known causes and few effective treatments, SFPN has a clear pathology and is known to be caused by specific medical conditions, some of which can be treated and sometimes cured. The study from Massachusetts General Hospital (MGH) researchers will appear in the journal PAIN and has been released online.
"This provides some of the first objective evidence of a mechanism behind some cases of fibromyalgia, and identifying an underlying cause is the first step towards finding better treatments," says Anne Louise Oaklander, MD, PhD, director of the Nerve Injury Unit in the MGH Department of Neurology and corresponding author of the Pain paper.
The term fibromyalgia describes a set of symptoms – including chronic widespread pain, increased sensitivity to pressure, and fatigue – that is believed to affect 1 to 5 percent of individuals in Western countries, more frequently women. While a diagnosis of fibromyalgia has been recognized by the National Institutes of Health and the American College of Rheumatology, its biologic basis has remained unknown. Fibromyalgia shares many symptoms with SFPN, a recognized cause of chronic widespread pain for which there are accepted, objective tests.
Designed to investigate possible connections between the two conditions, the current study enrolled 27 adult patients with fibromyalgia diagnoses and 30 healthy volunteers. Participants went through a battery of tests used to diagnose SFPN, including assessments of neuropathy based on a physical examination and responses to a questionnaire, skin biopsies to evaluate the number of nerve fibers in their lower legs, and tests of autonomic functions such as heart rate, blood pressure and sweating.
The questionnaires, exam assessments, and skin biopsies all found significant levels of neuropathy in the fibromyalgia patients but not in the control group. Of the 27 fibromyalgia patients, 13 had a marked reduction in nerve fiber density, abnormal autonomic function tests or both, indicating the presence of SFPN. Participants who met criteria for SFPN also underwent blood tests for known causes of the disorder, and while none of them had results suggestive of diabetes, a common cause of SFPN, two were found to have hepatitis C virus infection, which can be successfully treated, and more than half had evidence of some type of immune system dysfunction.
"Until now, there has been no good idea about what causes fibromyalgia, but now we have evidence for some but not all patients. Fibromyalgia is too complex for a ‘one size fits all’ explanation," says Oaklander, an associate professor of Neurology at Harvard Medical School. "The next step of independent confirmation of our findings from other laboratories is already happening, and we also need to follow those patients who didn’t meet SFPN criteria to see if we can find other causes. Helping any of these people receive definitive diagnoses and better treatment would be a great accomplishment."
(Source: massgeneral.org)
Full body illusion is associated with a drop in skin temperature
Researchers from the Center for Neuroprosthetics at the Swiss Federal Institute of Technology (EPFL), Switzerland, show that people can be “tricked” into feeling that an image of a human figure — an “avatar” — is their own body. The study is published in the open-access journal Frontiers in Behavioral Neuroscience.
Twenty-two volunteers underwent a Full Body Illusion when they were stroked with a robotic device system while they watched an avatar being stroked in the same spot. The study is the first to demonstrate that Full Body Illusions can be accompanied by changes in body temperature.
Participants wore a 3D high-resolution head-mounted display to view the avatar from behind. They were then subjected to 40 seconds of stroking by a robot, on either their left or right back or on their left or right leg. Meanwhile, they were shown a red dot that moved synchronously on the same regions of the avatar.
After the stroking, the participants were prompted to imagine dropping a ball and to signal the moment when they felt that the ball would hit the floor. This allowed the researchers to objectively measure where the participants perceived their body to be.
The volunteers were asked questions about how much they identified with the avatar and where they felt the stroking originated from. Furthermore, to test for physiological changes during the illusion, the participants’ skin temperature was measured on four locations on the back and legs across 20 time points.
Results showed that stroking the same body part simultaneously on the real body and the avatar induced a Full Body Illusion. The volunteers were confused as to where their body was and they partly identified with the avatar. More than 70% of participants felt that the touch they had felt on their body was derived from the stroking seen on the avatar.
Data revealed a continuous widespread decrease in skin temperature that was not specific to the site of measurement and showed similar effects in all locations. The changes in body temperature “were highly significant, but very small,” write the authors in the study, adding that the decrease was in the range of 0.006-0.014 degrees Celsius.
The recorded temperature change was smaller than an earlier study found (0.24 degrees Celsius) that looked at fluctuations during rubber hand illusion, probably because the latter used a hand-held thermometer over longer periods and different regions of the body, the authors explain.
"When the brain is confronted with a multisensory conflict, such as that produced by the Full Body Illusion, the way we perceive our real body changes. This causes a decrease in our body temperature, " says Dr. Roy Salomon, a postdoctoral fellow at the EPFL and the lead author of the study.
The scientists also say that the field of cognitive neuroprosthetics carries great promise for new prosthetics that are based on a neuroscientific understanding of the link between body and mind.
"This study helps us to understand the brain mechanisms that underlie the bodily aspects of consciousness and idea of ‘self’. It may contribute to the design of novel prosthetic devices and treatment of pain, for example, after stroke, amputation, or tetraplegia," says Prof. Olaf Blanke, director of the newly founded Center for Neuroprosthetics.
"This type of research may also help to understand and treat psychiatric disorders, such as schizophrenia and depression. We hope that by identifying the mechanisms involved in these processes and how they are altered in psychosis we can help these patients," adds Dr. Salomon.
How to learn successfully even under stress
Predicting the weather under stress
The team from Bochum has examined 80 subjects, 50 per cent of whom were given a drug blocking mineralocorticoid receptors in the brain. The remaining participants took a placebo drug. Twenty participants from each group were subjected to a stress-inducing experience. Subsequently, all participants underwent a learning test, the so-called weather prediction task. The subjects were shown playing cards with different symbols and had to learn which combinations of cards meant rain and which meant sunshine. The researchers used MRI to record the respective brain activity.
Learning unconsciously or consciously
There are two different approaches to master the weather prediction test: some subjects tried consciously to formulate a rule that would enable them to predict sunshine and rain. Others learned unconsciously to give the right answer, following their gut feeling, as it were. The team of Lars Schwabe demonstrated in August 2012 that, under stress, the brain prefers unconscious to conscious learning. “This switch to another memory system happens automatically,” says Lars Schwabe. “It makes sense for the organism to react in this manner. Thus, learning efficiency can be maintained even under stress.” However, this works only with fully functional mineralocorticoid receptors. Once the researchers blocked these receptors by applying the drug Spironolactone, the participants switched over to the unconscious strategy less frequently, thus demonstrating a poorer learning efficiency.
Effects also visible in brain activity
These effects also became evident in MRI data. Usually, stress causes the brain activity to shift from the hippocampus – a structure for conscious learning – to the dorsal striatum, which manages unconscious learning. However, this stress-induced switch took place only in the placebo group, not in subjects who had been given the mineralocorticoid receptor blocker. Consequently, the mineralocorticoid receptors play a crucial role in enabling the brain to adapt to stressful situations.
(Image: Shutterstock)
Surgical Anesthetic Appears to Treat Drug-Resistant Depression
More study is needed, but isoflurane might provide alternative to electroconvulsive therapy
Although electroconvulsive therapy (ECT) has long been considered the most effective treatment of medication-resistant depression, millions of people who could benefit don’t take advantage of it because of the treatment’s side effects and public misperception of the procedure.
If the results of a campus-wide collaboration of University of Utah researchers are borne out by larger studies and trials, patients with refractory depression might one day have an alternative that is as effective as ECT but without the side effects – the surgical anesthetic drug isoflurane.
“We need to expand our research into a larger, multicenter trial, but if the results of our pilot study pan out, it would change the face of treating depression,” says Howard R. Weeks, M.D., assistant professor of psychiatry and first author on a study published July 26, 2013, in PLOS ONE online.
Also known as shock therapy, ECT is effective in 55 percent to 90 percent of depression cases, with significant reductions in symptoms typically occurring within two to four weeks. When medications work, they can take six to eight weeks to become effective. But ECT is associated with side effects including amnesia, concentration and attention problems, and other cognitive issues. Many people also mistakenly believe ECT is painful and causes brain damage, which has given the treatment a social stigma that makes millions of patients reluctant to have it. Isoflurane potentially offers an alternative to ECT that could help many of those people, according to Weeks and his colleagues from eight University of Utah departments and programs.
In a pilot study with 20 patients who received ECT treatments compared to eight patients who received the isoflurane treatments, the researchers found that both therapies provided significant reduction in symptoms of depression. Immediately following the treatments, ECT patients showed declines in areas of memory, verbal fluency, and processing speed. Most of these ECT-related deficits resolved by four weeks. However, autobiographical memory, or recall of personal life events, remained below pretreatment levels for ECT patients four weeks after the treatment. In contrast, the patients treated with isoflurane showed no real impairment but instead had greater improvements in cognitive testing than ECT patients both immediately and four weeks after the treatments.
In the mid-1980’s, researchers in Europe studied isoflurane as a potential depression therapy. Later studies by other scientists failed to confirm the results of the original work and isoflurane research fell out of favor. But these later studies didn’t adhere to the first study’s protocol regarding type of anesthetic, dosing size and number of treatments, according to Weeks, and he believes that’s why isoflurane’s antidepressant effects weren’t confirmed in subsequent trials. For their research, Weeks and his University of Utah colleagues followed the original study’s protocol.
“Our data reconfirm that isoflurane had an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial,” the researchers wrote.
Researchers don’t know what produces the relief of depression symptoms from ECT or isoflurane. Weeks believes further research might identify a molecular pathway that both therapies target and is responsible for the improvement in depression. One common effect of both ECT and isoflurane treatments is a brief state of low electrical activity in which the brain becomes unusually quiet. ECT induces a seizure to reach that state, but isoflurane does not. After inhaling the anesthesia, patients are “under” for about 45 minutes, with 15 minutes of that time being a deep state of unconsciousness, according to Weeks. This period of electrical rest for the brain may be a potential explanation for why ECT and isoflurane improve depression.
If isoflurane proves to be a viable alternative to ECT, a device invented by three University of Utah anesthesiology faculty members can make the anesthetic an even more attractive therapy. The Aneclear™ device (Anecare, Salt Lake City, UT) invented by Dwayne R. Westenskow, Ph.D., Derek J. Sakata, M.D., and Joseph A. Orr, Ph.D., from the University of Utah Department of Anesthesiology, uses hyperventilation and allows patients to rebreathe their own carbon dioxide (C02). Hyperventilation removes anesthesia from the lungs and C02 encourages blood flow to the brain, which encourages quicker removal of anesthetic. The Aneclear™ also minimizes or even eliminates vomiting, nausea, and extreme fatigue that some patients experience from anesthesia.
“With the Aneclear™, we can wake people up from the anesthesia much quicker,” Weeks says. “This makes the treatment a potentially viable clinical treatment by reducing the time required in an operating room.”
Weeks and his co-researchers now are looking for grants to fund a larger study that will include several U.S. centers.
(Source: healthcare.utah.edu)