Category Archives: Neuroscience

Neuroscience

Omega-3s Linked to Improved Brain Structure and Cognition at Midlife – Neuroscience News

Summary: Boosting omega-3 fatty acid intake helps to preserve brain health and improve cognition in middle age, a new study reports. For those with the Alzheimers associated APOE4 gene, omega-3 fatty acid intake was associated with greater hippocampal volume and less small vessel disease.

Source: UT San Antonio

Eating cold-water fish and other sources of omega-3 fatty acids may preserve brain health and enhance cognition in middle age, new evidence indicates.

Having at least some omega-3s in red blood cells was associated with better brain structure and cognitive function among healthy study volunteers in their 40s and 50s, according to research published online Oct. 5 inNeurology.

Faculty of The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and other investigators of the Framingham Heart Study conducted the analysis.

Studies have looked at this association in older populations. The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age, said Claudia Satizabal, PhD, assistant professor of population health sciences with the Glenn Biggs Institute for Alzheimers and Neurodegenerative Diseases at UT Health San Antonio. Satizabal is the lead author of the study.

Volunteers average age was 46. The team looked at the relation of red blood cell omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging. Researchers also studied the effect of omega-3 red blood cell concentrations in volunteers who carried APOE4, a genetic variation linked to higher risk of Alzheimers disease.

The study of 2,183 dementia- and stroke-free participants found that:

Researchers used a technique called gas chromatography to measure docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations from red blood cells. The omega-3 index was calculated as DHA plus EPA.

Omega-3 fatty acids such as EPA and DHA are key micronutrients that enhance and protect the brain, said study coauthor Debora Melo van Lent, PhD, postdoctoral research fellow at the Biggs Institute. Our study is one of the first to observe this effect in a younger population. More studies in this age group are needed.

The team divided participants into those who had very little omega-3 red blood cell concentration and those who had at least a little and more.

We saw the worst outcomes in the people who had the lowest consumption of omega-3s, Satizabal said. So, that is something interesting. Although the more omega-3 the more benefits for the brain, you just need to eat some to see benefits.

Researchers dont know how DHA and EPA protect the brain. One theory is that, because those fatty acids are needed in the membrane of neurons, when they are replaced with other types of fatty acids, thats when neurons (nerve cells) become unstable. Another explanation may have to deal with the anti-inflammatory properties of DHA and EPA.

Its complex. We dont understand everything yet, but we show that, somehow, if you increase your consumption of omega-3s even by a little bit, you are protecting your brain, Satizabal said.

Its encouraging that DHA and EPA also protected APOE4 carriers brain health. Its genetics, so you cant change it, Melo van Lent said, referring to the vulnerability of this risk group.

So, if there is a modifiable risk factor that can outweigh genetic predisposition, thats a big gain.

Author: Will SansomSource: UT San AntonioContact: Will Sansom UT San AntonioImage: The image is in the public domain

Original Research: The findings will appear in Neurology

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Omega-3s Linked to Improved Brain Structure and Cognition at Midlife - Neuroscience News

Neuroscience

Inflammatory Breast Cancer Patients at Higher Risk of Cancer Spread to the Brain – Neuroscience News

Summary: Individuals with a rare type of breast cancer called inflammatory breast cancer are at greater risk of their cancer spreading to the brain.

Source: Wiley

New research indicates that among individuals with breast cancer, those with a rare subtype called inflammatory breast cancer face a higher risk that their cancer will spread, or metastasize, to the brain.

The study is published byWileyonline inCANCER, a peer-reviewed journal of the American Cancer Society.

Studies have demonstrated higher rates of brain metastases in patients with inflammatory breast cancer, but detailed information is lacking. To provide insights into the incidence and risk factors for brain metastases in this patient population, Laura E.G. Warren, MD, of the Dana-Farber Cancer Institute, and her colleagues analyzed data on 372 patients with stage III inflammatory breast cancer and 159 with stage IV inflammatory breast cancer.

Over a median follow-up of 5 years, the incidence of brain metastases at 1, 2, and 5 years was 5%, 9%, and 18% among patients who presented with stage III disease, and 17%, 30%, and 42% among those with stage IV disease.

Patients with triple-negative breast cancer faced a particularly high risk, and when they did experience brain metastases, their survival time was shorter than those with hormone receptorpositive or HER2-positive breast cancer who experienced brain metastases.

Higher risks of brain metastases were also seen in patients whose cancer had metastasized to other parts of the body besides the brain, especially when this occurred at a young age.

The relatively high incidence of brain metastases seen in the study population highlights the need for future research on the potential role for surveillance brain imaging for high-risk patients. There is an open, phase II, single armstudyat Dana-Farber Cancer Institute examining this question, said Dr. Warren.

It also emphasizes the need to obtain brain imaging in patients with inflammatory breast cancer presenting with neurologic symptoms given the high incidence of brain metastases in this population.

Most patients in this study who were diagnosed with brain metastases had neurologic symptoms, but because some patients may have undetected, asymptomatic brain metastases, the true incidence in patients with inflammatory breast cancer is likely even higher than what Dr. Warren and her colleagues observed.

An accompanyingeditorialnotes that when considering whether to implement routine brain imaging tests in patients with inflammatory breast cancer, it will be important to determine whether earlier detection of brain metastases leads to improvements in both survival and quality of life.

Author: Sara Henning-StoutSource: WileyContact: Sara Henning-Stout WileyImage: The image is in the public domain

Original Research: Open access.Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer by Laura E.G. Warren et al. CANCER

Abstract

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer

Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC.

The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS.

A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6years) and 17%, 30%, and 42% in stage IV patients (1.8years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS.

Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

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Neuroscience

New Star Rating System Helps People Make Informed Decisions About Diet and Healthy Habits – Neuroscience News

Summary: A new meta-analysis focuses on what we know, and what we dont know about whats good and bad for our health.

Source: IHME

A new set of meta-analysesclarifies the often complex and contradictory health guidance linking certain diets, behaviors, and conditions to illness.

The analyses, conducted by researchers from theInstitute for Health Metrics and Evaluation (IHME) at the University of Washingtons School of Medicine, were published today inNature Medicine.

IHME analyzed the strength of the evidence for 180 pairs of risk factors and health outcomes such as smoking and lung cancer, diet low in vegetables and type 2 diabetes, and high systolic blood pressure and ischemic heart disease.

The findings are presented in an easy-to-understand star rating system showing the strength of evidence for each link.

The new star rating system aims to help people make personal health decisions, inform health policy, and guide future research.

There has been extensive research on the links between various risks and health outcomes, but findings are often very different across studies, explained Dr. Christopher Murray, Director of the Institute for Health Metrics and Evaluation and a lead author of the study.

One of the goals of this new star rating system is to clear up confusion and help consumers make informed decisions about diet, exercise, and other activities that can affect their long-term health.

In many areas, IHME found that the link between a risk factor and a health outcome was weaker than some might believe. Nearly two-thirds of the risk-outcome pairs investigated 112 out of 180 received only a one- or two-star rating.

These include widely publicized pairings such as diet high in unprocessed red meat and ischemic stroke (one star). In other cases, IHMEs analysis confirmed widely held consensus.

Eight risk-outcome pairs received a five-star rating, including smoking and lung cancer and high systolic blood pressure and ischemic heart disease. A list of the star ratings, including a data visualization tool, can be found onIHMEs website.

Additional star ratings will be added in the near future.

The analysis takes into account both the magnitude of risk shown by studies to date, as well as the consistency of findings between those studies.

The star ratings are based on the most conservative interpretation of the available evidence, to limit the impact of error or bias in the underlying data. A one-star rating indicates that there may be no true association between the behavior or condition and the health outcome.

Two stars indicates the behavior or condition is at least associated with a 0-15% change in the likelihood of a health outcome, while three stars indicates at least a 15-50% change, four stars indicates at least a 50-85% change, and five stars indicates a more than 85% change.

For example, the five-star rating for smoking and lung cancer means that smoking increases the likelihood of developing or dying of lung cancer by more than 85%. At the other end of the scale, the one-star rating for red meat and ischemic stroke means that there may not be an association in this case, because studies of this link have produced inconsistent results.

Notable ratings from the study include:

In addition to helping consumers, our analysis can guide policymakers in developing health and wellness education programs, so that they focus on the risk factors with the greatest impact on health, said Dr. Emmanuela Gakidou, Professor of Health Metrics Sciences at the Institute for Health Metrics and Evaluation and a lead author of the study.

Health researchers can also use this analysis to identify areas where current evidence is weak and more definitive studies are needed. The IHME researchers also note that while the meta-analytical approach employed by this study should not replace expert deliberation, it can provide useful input for expert committees and advisory groups making formal health policy recommendations.

IHMEs analysis, which draws from the landmarkGlobal Burden of Disease study, which marks 30 years this year, will be updated on a regular basis.

As a result of constantly evolving research, the star ratings may change as more data becomes available. This is particularly the case for pairings with low star ratings due to limited or contradictory research.

On the other hand, high star ratings are unlikely to change significantly because the evidence is already strong.

Author: Connie KimSource: IHMEContact: Connie Kim IHMEImage: The image is in the public domain

Original Research: The findings will appear in Nature Medicine

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Neuroscience

Vegetarians More Likely to Be Depressed Than Meat-Eaters – Neuroscience News

Summary: A new study reveals vegetarians are two times more likely to suffer from depression than those who eat meat. While nutrition plays a role in depressive symptoms, researchers say social factors and upset over the treatment of animals contribute to symptoms of depression.

Source: The Conversation

Vegetarians have around twice as many depressive episodes as meat-eaters, according to anew study.

The study, based on survey data from Brazil, chimes withearlier researchthat found higher rates of depression among those who forgo meat. However, the new study suggests that this link exists independent of nutritional intake.

It may seem straightforward to look at a link between a diet and specific health problems and assume that the former is causing the latter via some form of nutritional deficiency.

Yet the new analysis, published in the Journal of Affective Disorders, took into account a wide range of nutritional factors, including total calorie intake, protein intake, micronutrient intake, and the level of food processing. This suggests that the higher rates of depression among vegetarians are not caused by the nutritional content of their diet.

So what might explain the link between vegetarianism and depression? Is there some non-nutritional mechanism that makes the former cause the latter? Or is the relationship down to something else entirely?

First, it is possible that being depressed causes people to be more likely to become vegetarian rather than the other way around. Thesymptoms of depressioncan include rumination on negative thoughts, as well as feelings of guilt.

Assuming that depressed and non-depressed people are equally likely to encounter the upsetting truth of slaughterhouses and factory farming, it is possible that depressed people are more likely to ruminate on those thoughts, and more likely to feel guilty for their part in creating the demand.

The depressed vegetarian, in this case, is not necessarily wrong to think this way. While depression is sometimes characterised as having unrealistically negative perceptions,there is evidence to suggestthat people with mild to moderate depression have more realistic judgments about the outcome of uncertain events and more realistic perceptions of their own role and abilities.

In this case, there really iscruel treatment of animals in meat production. And this really is caused by consumer demand for cheap meat.

Second, it is possible that adhering to a vegetarian diet causes depression for reasons other than nutrition. Even if there is no happy nutrient lacking in a vegetarian diet, it could be the case that forgoing meat causes depression through other means.

For example, adopting a vegetarian diet might affect ones relationship with others and involvement in social activities, and sometimes may be associated withteasing or other forms of social ostracism.

Notably, the new study is based on survey data collected in Brazil, a countryfamous for its meat-heavy diet. Some survey data has pointed to asharp increase in vegetarianism in Brazil in recent years, going from 8% in 2012 to 16% in 2018. However, the recent paper surveyed over 14,000 Brazilians and found just 82 vegetarians scarcely more than half a percent.

One has to wonder if the same link between vegetarianism and depression would be observed in India or other countries where vegetarianism is more of a social norm. More importantly, as therate of vegetarianism increases in the UKand other developed countries, will we see the relationship disappear over time?

Finally, it is possible that neither vegetarianism nor depression cause the other, but both are associated with some third factor. This could be any number of characteristics or experiences that are associated with both vegetarianism and depression.

For example,women are more likely than men to be vegetarian,and to experience depression. However, the Brazilian study took sex into account, ruling out this particular third variable.

One variable that was not examined, but is plausibly linked to both vegetarianism and depression, is exposure to violent images of the meat industry. Preventing cruelty to animals is themost commonly cited reasonvegetarians give for avoiding meat.

Documentaries likeDominionandEarthlingsthat depict the cruelty in the meat industry cannot readily be described as feelgood films. One can easily imagine that a person who consumes this kind of media would become both vegetarian and, especially when most people choose to look the other way, depressed.

There are several possible reasons for the link between vegetarianism and depression. This new study suggests that vegetarian nutrition is not the cause of depression.

Instead, the vegetarian social experience may contribute to depression, depression may cause an increased likelihood of becoming vegetarian, or both vegetarianism and depression may be caused by a third variable, such as exposure to violent meat industry imagery.

Author: Chris BryantSource: The Conversation Contact: Chris Bryant The ConversationImage: The image is in the public domain

Original Research: Closed access.Association between meatless diet and depressive episodes: A cross-sectional analysis of baseline data from the longitudinal study of adult health (ELSA-Brasil) by Ingrid Kohl et al. Journal of Affective Disorders

Abstract

Association between meatless diet and depressive episodes: A cross-sectional analysis of baseline data from the longitudinal study of adult health (ELSA-Brasil)

The association between vegetarianism and depression is still unclear. We aimed to investigate the association between a meatless diet and the presence of depressive episodes among adults.

A cross-sectional analysis was performed with baseline data from the ELSA-Brasil cohort, which included 14,216 Brazilians aged 35 to 74years. A meatless diet was defined from in a validatedfood frequency questionnaire. The Clinical Interview Schedule-Revised (CIS-R) instrument was used to assess depressive episodes. The association between meatless diet and presence of depressive episodes was expressed as a prevalence ratio (PR), determined by Poisson regression adjusted for potentially confounding and/or mediating variables: sociodemographic parameters, smoking, alcohol intake, physical activity, several clinical variables, self-assessed health status,body mass index, micronutrient intake, protein, food processing level, dailyenergy intake, and changes in diet in the preceding 6months.

We found a positive association between the prevalence of depressive episodes and a meatless diet. Meat non-consumers experienced approximately twice the frequency of depressive episodes of meat consumers, PRs ranging from 2.05 (95%CI 1.004.18) in the crude model to 2.37 (95%CI 1.244.51) in the fully adjusted model.

Limitations.

The cross-sectional design precluded the investigation of causal relationships.

Depressive episodes are more prevalent in individuals who do not eat meat, independently of socioeconomic and lifestyle factors.Nutrient deficienciesdo not explain this association. The nature of the association remains unclear, and longitudinal data are needed to clarify causal relationship.

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Vegetarians More Likely to Be Depressed Than Meat-Eaters - Neuroscience News

Neuroscience

Detecting Alzheimers Disease in the Blood – Neuroscience News

Summary: A new blood sample test is capable of measuring the build-up of Alzheimers disease-associated amyloid-beta in the brain.

Source: Hokkaido University

Researchers from Hokkaido University and Toppan have developed a method to detect build-up of amyloid in the brain, a characteristic of Alzheimers disease, from biomarkers in blood samples.

Alzheimers disease is a neurodegenerative disease, characterised by a gradual loss of neurons and synapses in the brain. One of the primary causes of Alzheimers disease is the accumulation of amyloid (A) in the brain, where it forms plaques. Alzheimers disease is mostly seen in individuals over 65 years of age, and cannot currently be stopped or reversed. Thus, Alzheimers disease is a major concern for nations with aging populations, such as Japan.

A team of scientists from Hokkaido University and Toppan, led by Specially Appointed Associate Professor Kohei Yuyama at the Faculty of Advanced Life Science, Hokkaido University, have developed a biosensing technology that can detect A-binding exosomes in the blood of mice, which increase as A accumulates in the brain.

Their research was published in the journalAlzheimers Research & Therapy.

When tested on mice models, the A-binding exosome Digital ICATM(idICA) showed that the concentration of A-binding exosomes increased with the increase in age of the mice. This is significant as the mice used were Alzheimers disease model mice, where A builds up in the brain with age.

In addition to the lack of effective treatments of Alzheimers, there are few methods to diagnose Alzheimers. Alzheimers can only be definitively diagnosed by direct examination of the brainwhich can only be done after death. A accumulation in the brain can be measured by cerebrospinal fluid testing or by positron emission tomography; however, the former is an extremely invasive test that cannot be repeated, and the latter is quite expensive. Thus, there is a need for a diagnostic test that is economical, accurate and widely available.

Previous work by Yuyamas group has shown that A build-up in the brain is associated with A-binding exosomes secreted from neurons, which degrade and transport A to the microglial cells of the brain. Exosomes are membrane-enclosed sacs secreted by cells that possess cell markers on their surface.

The team adapted Toppans proprietary Digital Invasive Cleavage Assay (Digital ICATM) to quantify the concentration of A-binding exosomes in as little as 100 L of blood. The device they developed traps molecules and particles in a sample one-by-one in a million micrometer-sized microscopic wells on a measurement chip and detects the presence or absence of fluorescent signals emitted by the cleaving of the A-binding exosomes.

Clinical trials of the technology are currently underway in humans. This highly sensitive idICA technology is the first application of ICA that enables highly sensitive detection of exosomes that retain specific surface molecules from a small amount of blood without the need to learn special techniques; as it is applicable to exosome biomarkers in general, it can also be adapted for use in the diagnosis of other diseases.

Author: Sohail Keegan PintoSource: Hokkaido UniversityContact: Sohail Keegan Pinto Hokkaido UniversityImage: The image is in the public domain

Original Research: Open access.Immuno-digital invasive cleavage assay for analyzing Alzheimers amyloid -bound extracellular vesicles by Kohei Yuyamaet al. Alzheimers Research & Therapy

Abstract

Immuno-digital invasive cleavage assay for analyzing Alzheimers amyloid -bound extracellular vesicles

The protracted preclinical stage of Alzheimers disease (AD) provides the opportunity for early intervention to prevent the disease; however, the lack of minimally invasive and easily detectable biomarkers and their measurement technologies remain unresolved. Extracellular vesicles (EVs) are nanosized membrane vesicles released from a variety of cells and play important roles in cellcell communication. Neuron-derived and ganglioside-enriched EVs capture amyloid- protein, a major AD agent, and transport it into glial cells for degradation; this suggests that EVs influence A accumulation in the brain. EV heterogeneity, however, requires the use of a highly sensitive technique for measuring specific EVs in biofluid. In this study, immuno-digital invasive cleavage assay (idICA) was developed for quantitating target-intact EVs.

EVs were captured onto ganglioside GM1-specific cholera toxin B subunit (CTB)-conjugated magnetic beads and detected with a DNA oligonucleotide-labeled A antibody. Fluorescence signals for individual EVs were then counted using an invasive cleavage assay (ICA). This idICA examines the A-bound and GM1-containing EVs isolated from the culture supernatant of human APP-overexpressing N2a (APP-N2a) cells and APP transgenicmice sera.

The idICA quantitatively detected A-bound and GM1-containing EVs isolated from culture supernatants of APP-N2a cells and sera of AD model mice. The idICA levels of A-associated EVs in blood gradually increased from 3- to 12-month-old mice, corresponding to the progression of A accumulations in the brain of AD model mice.

The present findings suggest that peripheral EVs harboring A and GM1 reflect A burden in mice. The idICA is a valuable tool for easy quantitative detection of EVs as an accessible biomarker for preclinical AD diagnosis.

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Neuroscience

How the Smell of Food Can Enable Time Travel – Neuroscience News

Summary: Study explores the 3D printed flavor-based cues in memory recall during old age, finding the smells of certain foods from youth can prompt mental time travel to the past with an enhanced memory of early exposure to the foods.

Source: Lancaster University

Older people exposed to food flavors from their youth were able to time travel back to the past with an enhanced memory of the event.

The research entitled It took me back 25 years in one bound: self-generated flavor-based cues for self-defining memories in later life published in Human-Computer Interaction is by Professor Corina Sas of Lancaster University, Dr Tom Gayler, formerly of Lancaster University and Vaiva Kalnikait of Dovetailed Ltd. Their work explored the feasibility of 3D printed flavor-based cues for the recall of memories in old age.

Working with 12 older adults, they collected 72 memories, half involving food and half not involving food, each recalled twice. This ranged from barbecued mackerel at a golden wedding to eating strawberries in hospital after giving birth.

For food memory, the researchers worked with the participants to create bespoke flavor-based cues for each one. The 3D printed flavor-based cues are small, gel-like, edible balls, modeling the original food, which are easier to swallow with more intense flavors, without requiring all the ingredients and preparation.

Professor Sas said: Our outcomes indicated that personalized 3D printed flavor-based cues have rich sensorial and emotional qualities supporting strong recollective retrieval, especially when they distinctively match the food in the original experience and prompt emotionally positive self-defining memories.

All the participants were able to provide rich sensory accounts when prompted by flavour-based cues, with most of the details not being present in the earlier free recall.

Remembering a Green Thai curry dinner in Cambodia, one participant remembered: We went into the kitchen area, which was very basic and preparing all sorts of types of green vegetables, which I have no idea what they were, sitting on the floor. And then we would help cook them, stir fry them, and then we would help dish them up

But after being exposed to the 3D printed flavor-based cue of the Green Thai curry, the participant gave a more detailed memory of the chopping noises of cutting up the vegetables, me sitting on the floor cross legged with my friend, chatting together. And then when we went out, put stuff on the tables, the rest of the group coming out and we sit on long tables outside, the front of the school, so its outside in the open air to eat.

A striking outcome was the large number of memories cued by flavors that were recalled with strong feelings of being brought back in time.

Participants said: The roast beef and horseradish cue took me back 25 years in one bound . . .I could place myself at the table in the room . . .I ate that, and that actually provoked out of all the memories, quite a strong reaction actually. Just suddenly I was back.

Interestingly, the mere act of eating the cue was seen as a bodily re-enactment of the original event: It just kind of triggers a few more sensations. Perhaps when youre tasting it, you imagine yourself there.

The researchers say their research has particular relevance for dementia. Participants talked about the importance of food memories based on their own experiences of caring for the loved ones.

One participant whose mother has Alzheimers said: As soon as she smelled and tasted the food, she would say something like, Oh, this is like old fashioned food. This takes me back. She felt that it was something that she had had a long time ago.

Another participant suggested a scrapbook of food memories to trigger recollections of past events in people with dementia.

Professor Sas said: The 3D printed flavours cued recollective retrieval, eliciting sensorially rich and strong positive emotional experiences that participants deeply enjoyed.

Dr Gayler said: Working alongside people to create flavour-based cues highlighted how powerful but under used this connection is. Our design approach helped bridge this gap and showed the potential for future applications to create rich, multi-sensory memory aides.

Dr Vaiva Kalnikaitsaid: We finally have technology that can help re-construct memories using the flavour and scent of different foods in very compact shapes. These are the strongest cues to help us remember.

Author: Gillian WhitworthSource: Lancaster UniversityContact: Gillian Whitworth Lancaster UniversityImage: The image is credited to Lancaster University

Original Research: Closed access.It took me back 25 years in one bound: self-generated flavor-based cues for self-defining memories in later life by Corina Sas et al. Human-Computer Interaction

Abstract

It took me back 25 years in one bound: self-generated flavor-based cues for self-defining memories in later life

those short, plump little cakes called petites madeleines [] I raised to my lips a spoonful of the tea in which I had soaked a morsel of the cake. No sooner had the warm liquid, and the crumbs with it, touched my palate, a shudder ran through my whole body [] an exquisite pleasure had invaded my senses [] and suddenly the memory returns. The taste was that of the little crumb of madeleine which on Sunday mornings at Combray [] when I went to say good day to her in her bedroom, my aunt Lonie used to give me, dipping it first in her own cup of real or of lime-flower tea [] when from a long-distant past nothing subsists, after the people are dead, after the things are broken and scattered, still, alone, more fragile, but with more vitality, more unsubstantial, more persistent, more faithful, the smell and taste of things remain poised a long time, like souls, ready to remind us [] the vast structure of recollection(Proust,2006, pp. 6163).

The above quote captures the evocative power of chemical senses for triggering memory recall with a feeling of traveling back in time, or the so-calledProust phenomenon.

While the phenomenon has been explored mostly in relation to the sense of smell, Prousts account involves also the sense of taste (Gibson,2016) as shown in our introductory quote and this additional sentence: the sight of the little madeleine had recalled nothing to my mind before I tasted it(Proust,2006, p. 63).

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Neuroscience

Mechanism for the Antidepressant Effect of Ketamine Revealed – Neuroscience News

Summary: Those with treatment-resistant depression showed significant improvement in symptoms and became more receptive to positive experiences following a one-week ketamine treatment regimen.

Source: Paris Brain Institute

Researchers from Inserm, CNRS, Sorbonne University and clinicians from the AP-HP and at Paris Brain Institute identified one of the mechanisms explaining ketamine effect as an antidepressant.

Ketamine, usually used as an anesthetic, was administered to patients with severe resistant depression. This treatment led patients to present an increased ability to overcome their negative beliefs about themselves and the world when researchers presented them positive information.

These results, published in JAMA Psychiatry, open new therapeutic avenues for the management of antidepressant-resistant mood disorders.

Depression is the most common psychiatric disorder: it is estimated that 5 to 15% of the French population will experience a major depressive episode during their lifetime. All age groups and all social backgrounds are affected.

The disease is characterized by sadness and loss of hedonic feelings that positive events do not improve. Depressed patients progressively develop negative beliefs about themselves, the world, and the future, that may develop into suicidal thoughts. These negative beliefs remain even when the patient receives positive information.

About one-third of people with depression do not respond to the most prescribed antidepressants, leading to a diagnosis of treatment-resistant depression (TRD). For these people, finding new and effective therapies is a priority.

Ketamine, a commonly used anesthetic, has been shown to influence resistant depression. While conventional antidepressant treatments take time to be efficient (on average three weeks), ketamine has a rapid antidepressant effect, only a few hours after administration. The mechanisms associated with this fast-acting antidepressant effect are still unknown.

To identify these mechanisms, Dr. Hugo Bottemanne and the research team co-led at the Paris Brain Institute by Pr Philippe Fossati and Liane Schmidt, Inserm researcher, coordinated a clinical study involving 26 antidepressant-resistant patients (TRD) and 30 healthy controls.

During the protocol, patients and healthy subjects were first asked to estimate the probability of 40 negative events which could occur in their lives (e.g., have a car accident, get cancer, or lose their wallet).

After being informed of the actual occurrence risks in the general population, patients and healthy subjects were again asked to estimate the probability of these events occurring in their lives. The research team was interested in the updating of beliefs after getting information.

Results showed that healthy subjects tended to update their initial beliefs more after receiving factual and positive information, which was not the case in the depressed patient population.

In the suite of the study, TRD patients received three administrations of ketamine at a subanesthetic dose (0.5 mg/kg over 40 minutes) in one week.

Only four hours after the first administration, patients ability to update their beliefs after receiving a positive information was increased. They became less sensitive to negative information and recovered an ability to update their knowledge com parable to that of control subjects.

Moreover, improvement in depressive symptoms after ketamine treatment was associated with these changes in belief updating, suggesting a link between clinical improvement and changes in this cognitive mechanism. In other words, the more patients belief updating ability was increased, the greater the improvement in symptoms was.

In conclusion, in this study, patients with antidepressant-resistant depression showed a significant decrease in symptoms and became more receptive to positive experiences after one week of ketamine treatment.

This work highlights for the first time a cognitive mechanism potentially involved in the early effect of ketamine. It paves the way to new research on antidepressant therapies modulating the mechanisms of belief updating.

Author: Nicolas BrardSource: Paris Brain InstituteContact: Nicolas Brard Paris Brain InstituteImage: The image is in the public domain

Original Research: Open access.Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression by Hugo Bottemanne et al. JAMA Psychiatry

Abstract

Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression

Importance

Clinical research has shown that persistent negative beliefs maintain depression and that subanesthetic ketamine infusions induce rapid antidepressant responses.

Objective

To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine.

Design, Setting, and Participants

This study used an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points. Observers were not blinded. Patients with treatment-resistant depression (TRD) and healthy volunteer participants aged 34 to 68 years were included. Patients with TRD were diagnosed with major depressive disorder or bipolar depression, had a Montgomery-sberg Depression Rating Scale score greater than 20, a Maudsley Staging Method score greater than 7, and failed to respond to at least 2 prior antidepressant trials. Exclusion criteria were any other psychiatric, neurological, or neurosurgical comorbidities, substance use or addictive disorders, and recreational ketamine consumption. Data were collected from January to February 2019 and from May to December 2019, and data were analyzed from January 2020 to July 2021.

Exposures

Patients with TRD were observed 24 hours before single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was 1 week after the first infusion. Healthy control participants were observed twice 1 week apart without ketamine exposure.

Main Outcomes and Measures

Montgomery-sberg Depression Rating Scale score and belief updating after belief updating when patients received good news and bad news measured by a cognitive belief-updating task and mathematically formalized by a computational reinforcement learning model.

Results

Of 56 included participants, 29 (52%) were male, and the mean (SEM) age was 52.3 (1.2) years. A total of 26 patients with TRD and 30 control participants were included. A significant grouptesting time pointnews valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: =0.91; 95% CI, 1.58 to 0.24;t216=2.67;P=.008) than controls. Computational modeling showed that this effect was associated with asymmetrical learning rates (LRs) after ketamine treatment (good news LRs after ketamine, 0.51 [SEM, 0.04]; bad news LRs after ketamine 0.36 [SEM, 0.03],t25=3.8;P<.001) and partially mediated early antidepressant responses (patha*b: =1.00 [SEM, 0.66];t26=1.53;z=1.98;P=.04).

Conclusions and Relevance

These findings provide novel insights into the cognitive mechanisms of the action of ketamine in patients with TRD, with promising perspectives for augmented psychotherapy for individuals with mood disorders.

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Mechanism for the Antidepressant Effect of Ketamine Revealed - Neuroscience News

Neuroscience

Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry – Yale News

Kristen Brennand

Kristen Brennand, who in her research integrates expertise in genetics, neuroscience, and stem cells to identify the mechanisms that underlie brain disease, was recently appointed the Elizabeth Mears and House Jameson Professor of Psychiatry.

She is also co-director of the Yale Science Fellows Program, a Yale School of Medicine initiative aimed at recruiting, supporting, and promoting outstanding young scientists from groups traditionally underrepresented in science and medicine.

Brennand completed her Ph.D. at Harvard University in the laboratory of the noted stem cell biologist Dr. Douglas Melton. During her postdoctoral fellowship at the Salk Institute, she drew international notice for publishing the first cellular model for schizophrenia. She developed a new method for reprogramming skin samples from patients into human induced pluripotent stem cells and then she differentiated these stem cells into neurons. Her initial report demonstrated that neurons derived from schizophrenia patients had profound deficits in synaptic connectivity, i.e., were less well connected to each other.

While on the faculty at the Icahn School of Medicine at Mount Sinai, Brennand developed a highly productive laboratory and a network of collaborations. By combining stem cell biology, psychiatric genetics, and neurobiology, she pioneered a new approach to studying brain disease. She and her collaborators shed light on the genetics and biology of schizophrenia, bipolar disorder, and other conditions. She was interim director of the Pamela Sklar Division of Psychiatric Genomics and then director of the Alper Stem Cell Center.

Although Brennand arrived at Yale during the pandemic, she rapidly established a productive laboratory, created new interdepartmental collaborations, and distinguished herself as a valued teacher and mentor. Her laboratory also is quite well funded with competitive grants from the National Institutes of Health (NIH).

She also has received numerous honors. The Brain and Behavior Research Foundation awarded her the Maltz Prize for Schizophrenia Research and elected her to its Scientific Council. This year, she was elected to the Connecticut Academy of Science and Engineering and named as a finalist for the 2022 Blavatnik Awards for Young Scientists. She also has developed a reputation as a mentor to her trainees and other young scientists. In 2019, she received the Friedman Brain Institute Neuroscience Mentorship Distinction Award. She serves as a standing member of NIH study section and the editorial boards of seven journals in psychiatry, stem cell biology, and neuroscience.

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Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry - Yale News

Neuroscience

NYU Neuro Grad Program – Home

Understanding the brain is one of the great scientific challenges. How does the nervous system allow us to sense, move, learn, decide, remember, and think? How are the underlying neural circuits built by genetic and molecular programs? How do neurons communicate via synapses to transmit and store information? What goes wrong in neurodevelopmental disorders like autism and schizophrenia, and in neurodegenerative diseases like Alzheimers and Parkinsons disease? And how can we model neurons, circuits and systems to better understand the brain?Graduate students in our PhD program in neuroscience are addressing these questions at labs located across NYU, using cutting-edge tools drawn from genetics, molecular biology, biochemistry, electrophysiology, microscopy, computer science, data science, and mathematics.This website is designed for you to learn about graduate training in neuroscience at NYU.Our program arises from two cooperative centers located just a few city blocks apart: the Center for Neural Science (CNS) and the Neuroscience Institute (NI). CNS, located at NYUs Washington Square campus, is home to core neuroscience labs, has affiliate labs in biology, psychology, physics and data science, and is NYUs portal for undergraduate neuroscience education. The NI is located at NYUs school of medicine and houses additional core neuroscience labs, as well as affiliates from clinical departments and the Nathan Kline Institute. Together, CNS and NI serve as the joint pillars of graduate training in neuroscience at NYU, with research spanning genetic, molecular, cellular, developmental, systems, behavioral, and computational levels. Prospective graduate students apply through a single online portal and applications are jointly reviewed by a single admissions committee that spans CNS and NI.

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NYU Neuro Grad Program - Home

Neuroscience

Neuroscience | OhioHealth

At OhioHealth, we provide the most comprehensive neuroscience care to diagnose, treat and heal patients with conditions like ALS, multiple sclerosis, Parkinsons disease, epilepsy, spine pain, stroke and more. We involve the highest-skilled specialists, the latest medical advancements, clinical trials and exclusive wellness programs to develop individualized treatment plans.

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Neuroscience | OhioHealth