An alternative neural mechanism for treating anxiety disorders through safety signal learning.

In these times of political polarization all over the world, over one third of all people experience anxiety disorders, in which circumstances frequently are taken to be more threatening than they actually are. This makes understanding the inhibition of emotional over-reactivity an important goal of brain research. Meyer et al. make a significant contribution by identifying a pathway that engages the ventral hippocampus for the attenuation of threat responses through conditioned inhibition using neurons that are more active to safety and compound cues than threat cues. This pathway might be a target for therapeutic approaches. Their summaries:  

Significance

Although fear can contribute to survival, difficulty regulating threat responses can interfere with goal-directed activities and is the hallmark of anxiety disorders. These disorders are the most common psychiatric illnesses, affecting up to one-third of the population. In parallel studies across species, we identify a pathway that engages the ventral hippocampus for the attenuation of threat responses through conditioned inhibition. Conditioned inhibition relies on the specific involvement of ventral hippocampal neurons projecting to the prelimbic cortex in mice and homologous ventral hippocampal–dorsal anterior cingulate cortex functional connectivity in humans. These findings highlight a pathway for the inhibition of fear with the potential to enhance interventions for anxiety disorders by targeting an alternative neural circuitry through safety signal learning.

Abstract

Heightened fear and inefficient safety learning are key features of fear and anxiety disorders. Evidence-based interventions for anxiety disorders, such as cognitive behavioral therapy, primarily rely on mechanisms of fear extinction. However, up to 50% of clinically anxious individuals do not respond to current evidence-based treatment, suggesting a critical need for new interventions based on alternative neurobiological pathways. Using parallel human and rodent conditioned inhibition paradigms alongside brain imaging methodologies, we investigated neural activity patterns in the ventral hippocampus in response to stimuli predictive of threat or safety and compound cues to test inhibition via safety in the presence of threat. Distinct hippocampal responses to threat, safety, and compound cues suggest that the ventral hippocampus is involved in conditioned inhibition in both mice and humans. Moreover, unique response patterns within target-differentiated subpopulations of ventral hippocampal neurons identify a circuit by which fear may be inhibited via safety. Specifically, ventral hippocampal neurons projecting to the prelimbic cortex, but not to the infralimbic cortex or basolateral amygdala, were more active to safety and compound cues than threat cues, and activity correlated with freezing behavior in rodents. A corresponding distinction was observed in humans: hippocampal–dorsal anterior cingulate cortex functional connectivity—but not hippocampal–anterior ventromedial prefrontal cortex or hippocampal–basolateral amygdala connectivity—differentiated between threat, safety, and compound conditions. These findings highlight the potential to enhance treatment for anxiety disorders by targeting an alternative neural mechanism through safety signal learning.

Great graphics - a review of cerebral cortex structure/folding from mice to humans.

I pass on this open source review article for the small number of MindBlog readers who might find it useful in their teaching. The summary color graphics of increasingly larger vertebrate brains (Mouse, Marmosett, Macaque, Chimpanzee, Human) show overall appearance and cell number, myelin patterns, and cortical parcellations. Here is the technical abstract:

Advances in neuroimaging and neuroanatomy have yielded major insights concerning fundamental principles of cortical organization and evolution, thus speaking to how well different species serve as models for human brain function in health and disease. Here, we focus on cortical folding, parcellation, and connectivity in mice, marmosets, macaques, and humans. Cortical folding patterns vary dramatically across species, and individual variability in cortical folding increases with cortical surface area. Such issues are best analyzed using surface-based approaches that respect the topology of the cortical sheet. Many aspects of cortical organization can be revealed using 1 type of information (modality) at a time, such as maps of cortical myelin content. However, accurate delineation of the entire mosaic of cortical areas requires a multimodal approach using information about function, architecture, connectivity, and topographic organization. Comparisons across the 4 aforementioned species reveal dramatic differences in the total number and arrangement of cortical areas, particularly between rodents and primates. Hemispheric variability and bilateral asymmetry are most pronounced in humans, which we evaluated using a high-quality multimodal parcellation of hundreds of individuals. Asymmetries include modest differences in areal size but not in areal identity. Analyses of cortical connectivity using anatomical tracers reveal highly distributed connectivity and a wide range of connection weights in monkeys and mice; indirect measures using functional MRI suggest a similar pattern in humans. Altogether, a multifaceted but integrated approach to exploring cortical organization in primate and nonprimate species provides complementary advantages and perspectives.

Brain aging reduced by elevating acetyl-CoA levels.

Acetyl coenzyme A (acetyl-CoA) is a central molecule in the energy metabolism of mitochondria in our cells. Currais et al. show that two Alzheimer's disease (AD) drug candidates known to reduce cognitive decline in a mouse model of AD increase acetyl-CoA levels and preserve mitochondrial function. Here is their technical abstract:

Because old age is the greatest risk factor for dementia, a successful therapy will require an understanding of the physiological changes that occur in the brain with aging. Here, two structurally distinct Alzheimer's disease (AD) drug candidates, CMS121 and J147, were used to identify a unique molecular pathway that is shared between the aging brain and AD. CMS121 and J147 reduced cognitive decline as well as metabolic and transcriptional markers of aging in the brain when administered to rapidly aging SAMP8 mice. Both compounds preserved mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism. CMS121 and J147 increased the levels of acetyl-CoA in cell culture and mice via the inhibition of acetyl-CoA carboxylase 1 (ACC1), resulting in neuroprotection and increased acetylation of histone H3K9 in SAMP8 mice, a site linked to memory enhancement. These data show that targeting specific metabolic aspects of the aging brain could result in treatments for dementia.

The quiet brains of athletes

An interesting study by Kraus and collaborators shows that athletes have larger responses to specified sounds than non-athletes, due to a reduction in their level of background neural noise. Their brains are not as noisy as those of non-athletes. From their abstract:

Playing sports has many benefits, including boosting physical, cardiovascular, and mental fitness. We tested whether athletic benefits extend to sensory processing—specifically auditory processing—as measured by the frequency-following response (FFR), a scalp-recorded electrophysiological potential that captures neural activity predominately from the auditory midbrain to complex sounds...We measured FFRs to the speech syllable “da” in 495 student-athletes across 19 Division I teams and 493 age- and sex-matched controls and compared them on 3 measures of FFR amplitude: amplitude of the response, amplitude of the background noise, and the ratio of these 2 measures.

Athletes have larger responses to sound than nonathletes, driven by a reduction in their level of background neural noise...These findings suggest that playing sports increases the gain of an auditory signal by turning down the background noise. This mode of enhancement may be tied to the overall fitness level of athletes and/or the heightened need of an athlete to engage with and respond to auditory stimuli during competition.

Such a study cannot distinguish whether being an athlete changed the young people’s brains or whether they succeeded as athletes because they were better at sound processing from the start. Further work might resolve this, as well as determining whether older people can reshape their sound processing by becoming active.

Anti-immigration sentiment does not correlate with local democraphic changes.

Hill et al. analyze election results and demographic measures for almost 32,000 precincts in the states of Florida, Georgia, Michigan, Nevada, Ohio, Pennsylvania, and Washington. Influxes of non-citizen immigrants correlated with vote shift away from the anti-immigration candidate (Trump) in the 2016 election. A commentary by Enos notes, however that:

....If ethnic minority populations are segregated and those voters without day-to-day contact continue to react negatively against the minority group, then even a local positive correlation between diversity and liberal politics may not lead to long-term harmony for a society...if increasing diversity affects political outcomes, the relationship can point in two consequentially different directions: toward increased diversity liberalizing politics or toward increased diversity causing a reactionary backlash.

From Hill et al.:

Significance

In recent years, advanced industrial democracies have grown more ethnically and racially diverse. This increasing diversity has the potential to reshape voting behavior in those countries, in part because majority groups may react by shifting support toward anti-immigration candidates and parties. This paper considers whether local demographic changes in the United States were associated with pro-Republican shifts between 2012 and 2016, when the Republican presidential candidate was especially outspoken in opposition to immigration. By showing that demographic changes were not associated with shifts toward the Republican, this research indicates that local demographic changes are not on their own increasing support for anti-immigration candidates.

Abstract

Immigration and demographic change have become highly salient in American politics, partly because of the 2016 campaign of Donald Trump. Previous research indicates that local influxes of immigrants or unfamiliar ethnic groups can generate threatened responses, but has either focused on nonelectoral outcomes or analyzed elections in large geographic units, such as counties. Here, we examine whether demographic changes at low levels of aggregation were associated with vote shifts toward an anti-immigration presidential candidate between 2012 and 2016. To do so, we compile a precinct-level dataset of election results and demographic measures for almost 32,000 precincts in the states of Florida, Georgia, Michigan, Nevada, Ohio, Pennsylvania, and Washington. We employ regression analyses varying model specifications and measures of demographic change. Our estimates uncover little evidence that influxes of Hispanics or noncitizen immigrants benefited Trump relative to past Republicans, instead consistently showing that such changes were associated with shifts to Trump’s opponent.

Increased emotional reactivity in men with high hair testosterone concentrations.

As I was scanning the table of contents of the latest issue of the journal "Social Cognitive and Affective Neuroscience" the article whose abstract I pass on below jumped out at me. (This is because I feel more emotional and sexual when my androgen levels reach their highest point in a monthly cycle, with lower points in the cycle correlating with lower motivation and anhedonia.) From Klein et al.:

Testosterone has been linked to alterations in the activity of emotion neurocircuitry including amygdala, orbitofrontal cortex (OFC) and insula and diminished functional amygdala/prefrontal coupling. Such associations have only ever been studied using acute measures of testosterone, thus little is known about respective relationships with long-term testosterone secretion. Here, we examine associations between hair testosterone concentration (HTC), an index of long-term cumulative testosterone levels and neural reactivity during an emotional passive viewing task using functional magnetic resonance imaging (fMRI). Forty-six men viewed negative, positive and neutral pictures in the MRI. HTCs were assessed from 2 cm hair segments. The emotional paradigm elicited neural activation in the amygdala, insula and OFC. HTCs were associated with increased reactivity to negative pictures in the insula and increased reactivity to positive pictures in the OFC. We show an association of long-term testosterone levels with increased emotional reactivity in the brain. These results suggest a heightened emotional vigilance in individuals with high trait testosterone levels.

We’ve just had the best decade (and year) in human history. Seriously

To provide a faintly upbeat end of the year post, I want to point to a Matt Ridley piece in The Spectator that provides a bit of a tonic for our times, by pointing out facts that haven't made the news, because good news is no news. Bad things capture our attention while the world overall is still getting better. In the same vein, Nicholas Kristof does a NYTimes piece titled "This Has Been the Best Year Ever" which has some nice graphics describing amazing declines in poverty and infant deaths, and gains in literacy. Some clips from the Ridley piece:

Extreme poverty has fallen below 10 per cent of the world’s population for the first time...Global inequality has been plunging as Africa and Asia experience faster economic growth than Europe and North America; child mortality has fallen to record low levels; famine virtually went extinct; malaria, polio and heart disease are all in decline.

...we are getting more sustainable, not less, in the way we use the planet...some nations are beginning to use less stuff: less metal, less water, less land. Not just in proportion to productivity: less stuff overall...what if economic growth means using less stuff, not more?’ For example, a normal drink can today contains 13 grams of aluminium, much of it recycled. In 1959, it contained 85 grams. Substituting the former for the latter is a contribution to economic growth, but it reduces the resources consumed per drink...The quantity of all resources consumed per person in Britain (domestic extraction of biomass, metals, minerals and fossil fuels, plus imports minus exports) fell by a third between 2000 and 2017, from 12.5 tonnes to 8.5 tonnes. That’s a faster decline than the increase in the number of people, so it means fewer resources consumed overall.

Mobile phones have the computing power of room-sized computers of the 1970s. I use mine instead of a camera, radio, torch, compass, map, calendar, watch, CD player, newspaper and pack of cards. LED light bulbs consume about a quarter as much electricity as incandescent bulbs for the same light...Even in cases when the use of stuff is not falling, it is rising more slowly than expected. For instance, experts in the 1970s forecast how much water the world would consume in the year 2000. In fact, the total usage that year was half as much as predicted. Not because there were fewer humans, but because human inventiveness allowed more efficient irrigation for agriculture, the biggest user of water.

...despite the growing number of people and their demand for more and better food, the productivity of agriculture is rising so fast that human needs can be supplied by a shrinking amount of land...we use 65 per cent less land to produce a given quantity of food compared with 50 years ago. By 2050, it’s estimated that an area the size of India will have been released from the plough and the cow.

Since its inception, the environmental movement has been obsessed by finite resources. The two books that kicked off the green industry in the early 1970s, The Limits to Growth in America and Blueprint for Survival in Britain, both lamented the imminent exhaustion of metals, minerals and fuels. The Limits to Growth predicted that if growth continued, the world would run out of gold, mercury, silver, tin, zinc, copper and lead well before 2000...To this day none of those metals has significantly risen in price or fallen in volume of reserves, let alone run out.

A modern irony is that many green policies advocated now would actually reverse the trend towards using less stuff. A wind farm requires far more concrete and steel than an equivalent system based on gas. Environmental opposition to nuclear power has hindered the generating system that needs the least land, least fuel and least steel or concrete per megawatt.

As we enter the third decade of this century, I’ll make a prediction: by the end of it, we will see less poverty, less child mortality, less land devoted to agriculture in the world. There will be more tigers, whales, forests and nature reserves. Britons will be richer, and each of us will use fewer resources. The global political future may be uncertain, but the environmental and technological trends are pretty clear — and pointing in the right direction.

World in decline? New authoritarian age? - the dangers of declinism.

These are times of high anxiety for both Red and Blue state America. A powerful Op-Ed by Roger Cohen, in the wake of the British election, sees a coming Trump victory in 2010, and David Brooks suggests that voters will pick whichever candidate exhausts them less. Numerous articles outline an emerging world of authoritarian surveillance states that fail to engage the looming disaster of global warming.

Jeremy Adelman, director of the Global History Lab at Princeton University, offers an interesting essay, noting that the idea of decline is one thing the extremes of Left and Right agree upon. Adelman reviews the history of declinism, and describes the fate of several previous dire predictions about humanity's future that did not come to pass, from Malthus' 18th century essay to The Club of Rome's "The Limits to Growth of 1972.  (For a recent rebuttal of declinism, see Matt Ridley's essay in The Spectator: "We've just had the best decade in human history. Seriously.")

Here are some clips from Adelman's piece:

Declinisms share some traits. They have more purchase in times of turmoil and uncertainty. They are also prone to thinking that the circles of hell can be avoided only with a great catharsis or a great charismatic figure.

But most of all: they ignore signs of improvement that point to less drastic ways out of trouble. Declinists have a big blindspot because they are attracted to daring, total, all-encompassing alternatives to the humdrum greyness of modest solutions. Why go for partial and piecemeal when you can overturn the whole system?

One dissenting voice in the 1970s was Albert O Hirschman’s. He worried about the lure of doomsaying. Dire predictions, he warned, can blind big-picture observers to countervailing forces, positive stories and glimmers of solutions. There is a reason why: declinists confuse the growing pains of change with signs of the end of entire systems. Declinism misses the possibility that behind the downsizing old ways there might be new ones poking through.

Why the allure of declinism if history seldom conforms to the predictions? To Hirschman, it was traceable to a prophetic style, one that appealed to intellectuals drawn to ‘fundamentalist’ explanations and who preferred to point to intractable causes of social problems. For revolutionaries, what awaits is a utopian alternative. For reactionaries, what lies in wait is dystopia. The result is an ‘antagonistic’ mode of thinking, a belief that history swings from one big, integrated, all-encompassing system to another. Compared with modest advances, compromises and concessions – how boring! – the magnificent vision of a complete overhaul has so many charms.

The problem with declinism is that it confirms the virtues of our highest, impossible solutions to fundamental problems. It also confirms the disappointments we harbour in the changes we have actually made. This is not to say there aren’t deep-seated problems. But seeing them as evidence of ineluctable demise can impoverish our imaginations by luring us to the sirens of either total change or fatalism.

For the holiday season - the gift of self care

To acknowledge that today is a special one for a large fraction of humanity, I want to pass on Parker-Pope's description of suggestions by Korean Buddhist teacher Haemin Sunim - five simple steps to quiet the mind and soothe stress at any time of the year, all in the spirit of "be good to yourself first - then to others."

Breathe

Start by just taking a deep breath. Become mindful of your breathing. You’ll notice that when you begin, your breathing is shorter and more shallow, but as you continue, your breathing becomes deeper. Take just a few minutes each day to focus on your breathing. “As my breathing becomes much deeper and I’m paying attention to it, I feel much more centered and calm,” Haemin Sunim said. “I feel I can manage whatever is happening right now.”

Accept

Acceptance — of ourselves, our feelings and of life’s imperfections — is a common theme in “Love for Imperfect Things.” The path to self-care starts with acceptance, especially of our struggles. “If we accept the struggling self, our state of mind will soon undergo a change,” Haemin Sunim writes. “When we regard our difficult emotions as a problem and try to overcome them, we only struggle more. In contrast, when we accept them, strangely enough our mind stops struggling and suddenly grows quiet. Rather than trying to change or control difficult emotions from the inside, allow them to be there, and your mind will rest.”

Write

Begin to practice acceptance through a simple writing exercise. Write down the situation you must accept and all that you are feeling. Write down the things in your life that are weighing on you'''the goal is to leave it all on the paper. Now go to bed and when you wake up, choose the easiest task on the list to complete. “In the morning, rather than resisting, I will simply do the easiest thing I can do from the list,” Haemin Sunim said. “Once I finish the easiest task, it’s much easier to work on the second.”

Talk

Never underestimate the value of meaningful conversation for your well-being. Make time on a regular basis for a close, nonjudgmental friend...Choose someone who will listen without any kind of judgment...Once the story is released, you can see it more objectively, and you will know what it is you need to do.”

Walk

One of the easiest ways to care for yourself is to take a walk. Just walking...can distract your mind and create space between you and whatever is causing stress in your life... If you start walking, our physical energy changes and rather than dwelling on that story, you can pay attention to nature — a tree trunk, a rock. You begin to see things more objectively, and oftentimes that stress within your body will be released simply by walking.”

Is this what my grandson will be doing in a few years?

My seven year old grandson Sebastian is a performer, taking piano lessons and reminding me a bit of myself when I was doing the same thing at his age. I think the tenuous similarity in our experiences will soon evaporate, especially in a few years if he joins the world of YouTube "Creators." The following YouTube summary of most popular videos of 2019 lets me (the 77 year old retired professor) know I am living on Mars.

Setting back our epigenic age?

I would like to point to Josh Mitteldorf's Blog "Aging Matters", in particular "Pulsed Yamanaka Factors Set Back Epigenic Age." A clip:

There’s a preprint from David Sinclair’s Harvard laboratory, posted on BioRxiv but not yet published, with very encouraging news for those of us who think that resetting the epigenetic (methylation) clock is a path to anti-aging. They suggest that 3 of the 4 Yamanaka factors, administered in short pulses, can set back the Horvath methylation clock without turning functioning tissues back into stem cells. The same study offers evidence to support the hypothesis that the epigenetic clock is a lethal driver of aging, rather than an adaptive response to damage.

MindBlog reviews the HealthyMinds App

The Center for Healthy Minds at the University of Wisconsin, established by my former University of Wisconsin colleague Richard Davidson, is trying to export the results of its basic research into practical forms - workplace programs, school programs, and now an App for tablets or cell phones.

I've put the App on my iPhone, and want to report my experience of going through its sequence of mini-lectures and exercises, organized under five categories: Foundations, awareness, connection, insight, and purpose. The basic science presented and the exercises were familiar to me, and I was struck by how effectively the essence of each was presented in its most simple and accessible form. (I would have liked to have been able to see the brief voice lectures also offered in text form.) For example, the instruction most often seen for the exercise of paying attention to breathing suggest counting each breath, from one to nine or ten, then repeating, and returning to this practice when one notices having been distracted by other thoughts.  Why not just count to three, as instructed by the App.  It is more simple, and equally effective.  For each of the exercises, one can choose a sitting or active version (active meaning doing routine, but not novel, activities),  a male or female narrator, and varying duration from 5 to 30 min.  It was not until I had finished the available series of lectures and exercises and tried to go back to earlier stages and examine them in more detail that I encountered a requirement that a subscription be purchased (~$5/month, but see below).   If the ideas and exercises presented were less familiar to me, and I was not already fairly settled in my various practices, I'm sure I would purchase a subscription to the App.

(added note: Please see the comment below.  A subscription is not required to repeat the Foundations section I was describing. It is  offered for further engagement of the Awareness, Connection, Insight, and Purpose modules.) 

Favorite sentences

I have to pass on a few of the favorite sentences collected by book critic Dwight Garner from his 2019 list of books - you can get the citations from the article.

“Watch for the glamorous sentence that appears from nowhere — it might have plans for you.”

“If you don’t know the exact moment when the lights will go out, you might as well read until they do.”

“The one good thing about national anthems is that we’re already on our feet, and therefore ready to run.”

“How’re you doing,” a character asked in Ali Smith’s novel “Spring,” “apart from the end of liberal capitalist democracy?”

“Take a simpleton and give him power and confront him with intelligence — and you have a tyrant.”

In Robert Menasse’s sophisticated novel “The Capital,” set in Brussels, a character watched old nationalist ghosts rise in a tabloid culture, and commented: “He had been prepared for everything, but not everything in caricature.”...also from this novel...“Back in 1914, his grandfather had said, Brussels was the richest and most beautiful city in the world — then they came three times, twice in their boots with rifles, the third time in their trainers with cameras.”

Or, to let it all pass by...

Nabokov told an interviewer in 1974, “I don’t even know who Mr. Watergate is.”

And, I will add a favorite sentence of my own, from Pinker’s guide to writing “Sense of Style..”

"The key to good style, far more than obeying any list of commandments, is to have a clear conception of the make-believe world in which you’re pretending to communicate."

Our blood protein profiles change in the fourth, seventh and eighth decades of life

Lehallier et al. find that ~1,380 of the ~3,000 plasma proteins in blood samples from 4,263 people between the ages of 18 and 95 vary significantly with age, with big shifts occurring around the ages of 34, 60, and 78 - in the fourth, seventh and eighth decades of life:

Aging is a predominant risk factor for several chronic diseases that limit healthspan. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues, which supports a hypothesis that age-related molecular changes in blood could provide new insights into age-related disease biology. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18–95 years old) and developed a new bioinformatics approach that uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.

Our visual system uses recurrence in its representational dynamics

Fundamental work from Kietzmann et al. shows how recurrence - lateral and top-down feedback from higher to the more primary visual areas of the brain that first register visual input - is occurring during forming visual representations. This process is missing from engineering and neuroscience models that emphasize feedforward neural network models. (Click the link to the article and scroll down to see a fascinating video of their real time magnetoencephalography (MEG) measurements. ) 


Significance

Understanding the computational principles that underlie human vision is a key challenge for neuroscience and could help improve machine vision. Feedforward neural network models process their input through a deep cascade of computations. These models can recognize objects in images and explain aspects of human rapid recognition. However, the human brain contains recurrent connections within and between stages of the cascade, which are missing from the models that dominate both engineering and neuroscience. Here, we measure and model the dynamics of human brain activity during visual perception. We compare feedforward and recurrent neural network models and find that only recurrent models can account for the dynamic transformations of representations among multiple regions of visual cortex.

Abstract

The human visual system is an intricate network of brain regions that enables us to recognize the world around us. Despite its abundant lateral and feedback connections, object processing is commonly viewed and studied as a feedforward process. Here, we measure and model the rapid representational dynamics across multiple stages of the human ventral stream using time-resolved brain imaging and deep learning. We observe substantial representational transformations during the first 300 ms of processing within and across ventral-stream regions. Categorical divisions emerge in sequence, cascading forward and in reverse across regions, and Granger causality analysis suggests bidirectional information flow between regions. Finally, recurrent deep neural network models clearly outperform parameter-matched feedforward models in terms of their ability to capture the multiregion cortical dynamics. Targeted virtual cooling experiments on the recurrent deep network models further substantiate the importance of their lateral and top-down connections. These results establish that recurrent models are required to understand information processing in the human ventral stream.

More insight into metformin's beneficial effects on diabetes, aging, and several diseases.

A group at McMaster University has shown an effect of the diabetes drug metformin beyond its suppression of liver glucose production that might partially explain its beneficial effects on aging and a number of diverse diseases such as cognitive disorders, cancer and cardiovascular disease. (There are currently over 1,500 registered clinical trials to test the effects of metformin in aging and different diseases.) It induces the expression and secretion of growth differentiating factor 15 (GDF15) in mouse liver cells, a protein known to suppress appetite and cause weight loss.

I'm sorely tempted to try to get myself a prescription for the stuff! Here is the technical abstract of the article:

Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in refs. 1,2,3). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood1,2,3. Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system4. Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.

Heritable gaps between chronological age and brain age are increased in common brain disorders.

Kaufmann et al. have used machine learning on s large dataset to estimate robust estimation of individual biological brain ages on the basis of structural brain imaging features. The deviation between brain age and chronological age — termed the brain age gap — appears to be a promising marker of brain health. It was largest in schizophrenia, multiple sclerosis, dementia, and bipolar spectrum disorder. The authors also assessed the overlap between the genetic underpinnings of brain age gap and common brain disorders. The bottom line conclusion (from a very extensive and complex analysis) is that common brain disorders are associated with heritable patterns of apparent aging of the brain Their abstract:

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

Same-Sex behavior in animals - a new view.

Monk et al. offer a fresh perspective on the "problem" of how same-sex sexual behavior could have evolved. It is a problem only if different-sex sexual behavior is the baseline condition for animals, from which single-sex behavior has evolved. The authors suggest that same-sex behavior is bound up in the very origins of animal sex. It hasn’t had to continually re-evolve: It’s always been there. The arguments of Monk and collaborators are summarized in a review by Elbein:

Instead of wondering why same-sex behavior had independently evolved in so many species, Ms. Monk and her colleagues suggest that it may have been present in the oldest parts of the animal family tree. The earliest sexually reproducing animals may have mated with any other individual they came across, regardless of sex. Such reproductive strategies are still practiced today by hermaphroditic species, like snails, and species that don’t appear to differentiate, like sea urchins.

Over time, Ms. Monk said, sexual signals evolved — different sizes, colors, anatomical features and behaviors — allowing different sexes to more accurately target each other for reproduction. But same-sex behavior continued in some organisms, leading to diverse sexual behaviors and strategies across the animal kingdom. And while same-sex behavior may grant some evolutionary benefits, an ancient origin would mean those benefits weren’t required for it to exist.

But how has same-sex behavior stuck around? The answer may be that such behaviors aren’t as evolutionarily costly as assumed. Traditionally, Ms. Monk said, any mating behavior that doesn’t produce young is seen as a waste. But animal behavior often doesn’t fit neatly into an economic accounting of costs and benefits.

Here is the abstract of Monk et al.:

Same-sex sexual behaviour (SSB) has been recorded in over 1,500 animal species with a widespread distribution across most major clades. Evolutionary biologists have long sought to uncover the adaptive origins of ‘homosexual behaviour’ in an attempt to resolve this apparent Darwinian paradox: how has SSB repeatedly evolved and persisted despite its presumed fitness costs? This question implicitly assumes that ‘heterosexual’ or exclusive different-sex sexual behaviour (DSB) is the baseline condition for animals, from which SSB has evolved. We question the idea that SSB necessarily presents an evolutionary conundrum, and suggest that the literature includes unchecked assumptions regarding the costs, benefits and origins of SSB. Instead, we offer an alternative null hypothesis for the evolutionary origin of SSB that, through a subtle shift in perspective, moves away from the expectation that the origin and maintenance of SSB is a problem in need of a solution. We argue that the frequently implicit assumption of DSB as ancestral has not been rigorously examined, and instead hypothesize an ancestral condition of indiscriminate sexual behaviours directed towards all sexes. By shifting the lens through which we study animal sexual behaviour, we can more fruitfully examine the evolutionary history of diverse sexual strategies.

Something in the way we move.

Gretchen Reynolds points to work by Hug et al. suggesting that each of us has a unique muscle activation signature that can be revealed during walking and pedaling. Understanding movement patterns could help in improving and refining robotics, prosthetics, physical therapy and personalized exercise programs. On the darker side, a Chinese company (Watrix) is using computer vision to to enhance the recognition of individuals in crowds by their walking postures:

...its gait recognition solution “Shuidi Shenjian” ... will enable security departments to quickly search and recognize identities by their body shape and walking posture. The company notes that this product is highly effective when targets walk from a long distance or in weak light, cover their faces or wear different clothes, and would be a great supplement to current computer vision products.

Here is the complete abstract from Hug et al.:

Although it is known that the muscle activation patterns used to produce even simple movements can vary between individuals, these differences have not been considered to prove the existence of individual muscle activation strategies (or signatures). We used a machine learning approach (support vector machine) to test the hypothesis that each individual has unique muscle activation signatures. Eighty participants performed a series of pedaling and gait tasks, and 53 of these participants performed a second experimental session on a subsequent day. Myoelectrical activity was measured from eight muscles: vastus lateralis and medialis, rectus femoris, gastrocnemius lateralis and medialis, soleus, tibialis anterior, and biceps femoris-long head. The classification task involved separating data into training and testing sets. For the within-day classification, each pedaling/gait cycle was tested using the classifier, which had been trained on the remaining cycles. For the between-day classification, each cycle from day 2 was tested using the classifier, which had been trained on the cycles from day 1. When considering all eight muscles, the activation profiles were assigned to the corresponding individuals with a classification rate of up to 99.28% (2,353/2,370 cycles) and 91.22% (1,341/1,470 cycles) for the within-day and between-day classification, respectively. When considering the within-day classification, a combination of two muscles was sufficient to obtain a classification rate >80% for both pedaling and gait. When considering between-day classification, a combination of four to five muscles was sufficient to obtain a classification rate >80% for pedaling and gait. These results demonstrate that strategies not only vary between individuals, as is often assumed, but are unique to each individual.

Rival theories of consciousness being tested by large project.

In the first phase of a $20 million dollar project, six laboratories are going to run experiments with more than 500 participants to test two of the primary theories of consciousness:

The first two contenders are the global workspace theory (GWT), championed by Stanislas Dehaene of the Collège de France in Paris, and the integrated information theory (IIT), proposed by Giulio Tononi of the Uni-versity of Wisconsin in Madison. The GWT says the brain’s prefrontal cortex, which con-trols higher order cognitive processes like decision-making, acts as a central computer that collects and prioritizes information from sensory input. It then broadcasts the infor-mation to other parts of the brain that carry out tasks. Dehaene thinks this selection pro-cess is what we perceive as consciousness. By contrast, the IIT proposes that conscious-ness arises from the interconnectedness of brain networks. The more neurons interact with one another, the more a being feels conscious—even without sensory input. IIT proponents suspect this process occurs in the back of the brain, where neurons con-nect in a gridlike structure...Tononi and Dehaene have agreed to pa-rameters for the experiments and have reg-istered their predictions. To avoid conflicts of interest, the scientists will neither collect nor interpret the data. If the results appear to disprove one theory, each has agreed to admit he was wrong—at least to some extent

The labs, in the United States, Germany, the United Kingdom, and China, will use three techniques to record brain activity as volun-teers perform consciousness-related tasks: functional magnetic resonance imaging, electroencephalography, and electrocortico-graphy (a form of EEG done during brain sur-gery, in which electrodes are placed directly on the brain). In one experiment, research-ers will measure the brain’s response when a person becomes aware of an image. The GWT predicts the front of the brain will suddenly become active, whereas the IIT says the back of the brain will be consistently active.