Apathy can signal the onset of dementia years before other symptoms appear

Apathy can be a dangerous warning sign for many conditions tied to mental health. While the loss of interest and motivation typically signals the onset of depression, hormone changes, or other mental conditions, a new study finds it may also be a red flag for dementia. Researchers from the University of Cambridge say feelings of apathy can predict if someone will develop dementia years before symptoms like memory loss ever appear.

Frontotemporal dementia is one of the leading causes of dementia in younger patients. Doctors typically diagnose the condition in patients between 45 and 65 years-old. This form of cognitive decline can also affect behavior, language, and personality. Patients can begin to act more impulsively and engage in inappropriate or compulsive behavior.

One of the common threads in frontotemporal dementia cases is patients become apathetic, losing interest in things they normally do. Researchers say this isn’t depression, even though physicians may mistake it for another condition. The study finds frontotemporal dementia is triggered by shrinkage in particular regions in the front of the brain. The worse the shrinkage gets, the more apathetic patients become. While this will eventually lead to cognitive decline, study authors say the process can begin years and possibly decades before dementia becomes visible.

“Apathy is one of the most common symptoms in patients with frontotemporal dementia. It is linked to functional decline, decreased quality of life, loss of independence and poorer survival,” says Maura Malpetti, a cognitive scientist at Cambridge’s Department of Clinical Neurosciences, in a university release.

“The more we discover about the earliest effects of frontotemporal dementia, when people still feel well in themselves, the better we can treat symptoms and delay or even prevent the dementia.”

‘Brain shrinkage in areas that support motivation and initiative’

The study reveals that frontotemporal dementia can be a genetic condition. Nearly a third of patients with this form of dementia have family members who also had it too.

Researchers examined 304 healthy people who carry a faulty gene which can trigger frontotemporal dementia and 296 members of their family who have normal genes. The study followed each person for several years and most of the patients didn’t know whether they had the gene abnormality or not. Researchers monitored each person for changes in apathy, memory, and took MRI scans of their brains.

“By studying people over time, rather than just taking a snapshot, we revealed how even subtle changes in apathy predicted a change in cognition, but not the other way around,” Malpetti explains. “We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms.”

Apathy’s impact on the brain

The results reveal that people with this genetic mutation display more apathy than their relatives who don’t carry the defect. Over two years, this behavior increased significantly more than in people with normal genes. Apathy also predicted the onset of cognitive decline as patients approached the typical age dementia symptoms tend to appear.

“Apathy progresses much faster for those individuals who we know are at greater risk of developing frontotemporal dementia, and this is linked to greater atrophy in the brain. At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy. The amount of apathy predicted cognitive problems in the years ahead,” Professor Rogier Kievit says.

“From other research, we know that in patients with frontotemporal dementia, apathy is a bad sign in terms of independent living and survival. Here we show its importance in the decades before symptoms begin,” adds joint senior author Professor James Rowe.

Prof. Rowe says the study shows why it’s important to not only find out if someone is displaying apathy, but why they’re feeling this way.

“There are many reasons why someone feels apathetic. It may well be an easy to treat medical condition, such as low levels of thyroid hormone, or a psychiatric illness such as depression. But doctors need to keep in mind the possibility of apathy heralding a dementia, and increasing the chance of dementia if left unaddressed, particularly if someone has a family history of dementia,” he concludes.

“Treating dementia is a challenge, but the sooner we can diagnose the disease, the greater our window of opportunity to try and intervene and slow or stop its progress.”

The study appears in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.


Yes, more money will always make your life better, but that’s not all there is to happiness, says new study

by Alexandru Micu

In a twist that’s bound to surprise nobody, a new study finds that there isn’t actually any limit past which more money won’t make you happier. Yes, that sounds disheartening, but the authors also caution that it’s not the only thing that makes us happy by a long shot. Chasing money at the expense of everything else might actually make us less happy.

The relationship between wealth and happiness has always fascinated researchers. One widely-known bit of research in the past suggested that the magic number is $75,000 per year. You won’t gain more happiness by gaining more than that, it added. But if you’ve had to bear through the pandemic jobless or in a job you hate but had to take, struggling to make ends meet, while watching rich people ‘suffer’ in mansions with gardens or spending their holidays on private islands, you might not put too much stock in that idea.

New research agrees with you.

The more the merrier

“[The relationship between money and well-being is] one of the most studied questions in my field,” says Matthew Killingsworth, a senior fellow at Penn’s Wharton School who studies human happiness, lead author of the paper. “I’m very curious about it. Other scientists are curious about it. Laypeople are curious about it. It’s something everyone is navigating all the time.”

Killingsworth set out to answer the question with a wealth of data. The technique he used is called experience sampling, and it involves having people to fill out short surveys at random times of the day. These serve as ‘snapshots’ of their feelings and moods over time, and how these fluctuate.

All in all, he collected 1.7 million data points (‘snapshots’) from more than 33,000 participants aged 18 to 65 from the US through an app called Track Your Happiness that he developed. This allowed him to obtain measurements from each participant a few times every day, with check-in times being randomized for each participant. These were measured on a scale ranging from “very bad” to “very good”, and every participant also answered the question “Overall, how satisfied are you with your life?” (on a scale of “not at all” to “extremely”) at least once. These all measured evaluative well-being, he explains.

“It tells us what’s actually happening in people’s real lives as they live them, in millions of moments as they work and chat and eat and watch TV,” he explains.

But the study also tracked experienced well-being by asking about 12 specific feelings. Five were positive — confident, good, inspired, interested, and proud — and seven negative — afraid, angry, bad, bored, sad, stressed, and upset. Two other measures of life satisfaction collected on an intake survey were also factored in here. Evaluative well-being measures our overall satisfaction with life, while experienced well-being indicates how we feel in the moment.

All in all, Killingsworth says the findings suggest that there is no dollar value past which more money won’t matter to an individual’s well-being and happiness.

“It’s a compelling possibility, the idea that money stops mattering above that point, at least for how people actually feel moment to moment,” he adds . “But when I looked across a wide range of income levels, I found that all forms of well-being continued to rise with income. I don’t see any sort of kink in the curve, an inflection point where money stops mattering. Instead, it keeps increasing.”

“We would expect two people earning $25,000 and $50,000, respectively, to have the same difference in well-being as two people earning $100,000 and $200,000, respectively. In other words, proportional differences in income matter the same to everyone.”

Killingsworth used the logarithm of a person’s income, rather than the actual income, for his study. In essence, this takes into account how much money someone already has. This approach means that rather than being just as important for everyone, each dollar will matter less the more a person earns.

He found that higher earners are happier in part because they feel more in control over their life. More money means more choices, options, and possibilities in regards to how we live life and spend our time, as the pandemic brutally showed. Someone living paycheck to paycheck will have less autonomy over their choices than someone who’s better-off — such as not having to take any job, even if you dislike it, due to financial constraints. Still, in Killingsworth’s eyes, this doesn’t mean we should chase money, and I feel the same way.

“Although money might be good for happiness, I found that people who equated money and success were less happy than those who didn’t. I also found that people who earned more money worked longer hours and felt more pressed for time,” Killingsworth explains.

“If anything, people probably overemphasize money when they think about how well their life is going. Yes, this is a factor that might matter in a way that we didn’t fully realize before, but it’s just one of many that people can control and ultimately, it’s not one I’m terribly concerned people are undervaluing.”

He hopes the findings bring forth more pieces of that ever-elusive puzzle: what exactly makes us happy? Money definitely plays a part, but, according to the findings, only “modestly”, Killingsworth explains.

The paper has been published in the journal PNAS and on the Penn State University’s blog.

Eye Tests Predict Parkinson’s-Associated Cognitive Decline 18 Months Ahead

Simple vision tests can predict which people with Parkinson’s disease will develop cognitive impairment and possible dementia 18 months later, according to a study published in Movement Disorders.

The findings add to evidence that vision changes precede the cognitive decline that occurs in many, but not all, people with Parkinson’s disease.

In another study published in Communications Biology, the same research team found that structural and functional connections of brain regions become decoupled throughout the entire brain in people with Parkinson’s disease, particularly among people with vision problems.

The 2 studies together show how losses and changes to the brain’s wiring underlie the cognitive impairment experienced by many people with Parkinson’s disease.

“We have found that people with Parkinson’s disease who have visual problems are more likely to get dementia, and that appears to be explained by underlying changes to their brain wiring,” said lead author Angeliki Zarkali, MD, Dementia Research Centre, University College London Queen Square Institute of Neurology, London, United Kingdom. “Vision tests might provide us with a window of opportunity to predict Parkinson’s dementia before it begins, which may help us find ways to stop the cognitive decline before it’s too late.”

For the Movement Disorders paper, the researchers studied 77 patients with Parkinson’s disease and found that simple vision tests predicted who would go on to get dementia 1.5 years later. The study also found that those who went on to develop Parkinson’s dementia had losses in the wiring of the brain, including in areas relating to vision and memory. The researchers identified white matter damage to some of the long-distance wiring connecting the front and back of the brain, which helps the brain to function as a cohesive whole network.

The Communications Biology study involved 88 people with Parkinson’s disease (33 of whom had visual dysfunction and were thus judged to have a high risk of dementia) and 30 healthy adults as a control group, whose brains were imaged using MRI scans. The researchers found that people with Parkinson’s disease exhibited a higher degree of decoupling across the whole brain. Areas at the back of the brain, and less specialised areas, had the most decoupling in patients with Parkinson’s disease. Patients with Parkinson’s disease with visual dysfunction had more decoupling in some, but not all brain regions, particularly in memory-related regions in the temporal lobe.

The research team also found changes to the levels of some neurotransmitters in people at risk of cognitive decline, suggesting that receptors for those transmitters may be potential targets for new drug treatments for Parkinson’s dementia. Notably, while dopamine is known to be implicated in Parkinson’s, the researchers found that other neurotransmitters — acetylcholine, serotonin, and noradrenaline — were particularly affected in people at risk of cognitive decline.

“The 2 papers together help us to understand what’s going on in the brains of people with Parkinson’s who experience cognitive decline, as it appears to be driven by a breakdown in the wiring that connects different brain regions,” said Dr. Angeliki.

“Our findings could be valuable for clinical trials, by showing that vision tests can help us identify who we should be targeting for trials of new drugs that might be able to slow Parkinson’s — and ultimately if effective treatments are found, then these simple tests may help us identify who will benefit from which treatments,” said senior author Rimona Weil, MD, University College London.

References: https://onlinelibrary.wiley.com/doi/10.1002/mds.28477 and https://www.nature.com/articles/s42003-020-01622-9

Brain imaging study reveals blunted empathic response to others’ pain when following orders


A brain imaging study has found that inflicting pain on another person in compliance with an order is accompanied by reduced activation in parts of the brain associated with the perception of others’ pain. The study was published in NeuroImage.

There exists a well-documented psychological phenomenon where people will go to great lengths to comply with authority even if it means harming others. The most famous example is the Milgram experiment, where subjects pressed a button to deliver what they believed were increasingly painful electric shocks to strangers at the request of experimenters. While this experiment has been widely replicated, researchers Emilie A. Caspar and associates point out that studies have yet to uncover a neurological explanation for this effect.

Caspar and her colleagues set out to explore the possibility that causing someone pain under someone else’s direction reduces empathy for that pain. With a brain imaging study, they tested whether being coerced to inflict harm on someone would be associated with reduced activation in areas of the brain involved in the perception of others’ pain, when compared to inflicting the same harm out of one’s own free will.

The researchers recruited 40 subjects with an average age of 25 to partake in their study. The participants were paired up, and each took turns being the ‘agent’ and the ‘victim’ in a controlled experiment. During a series of trials, the agent had control of administering a mildly painful shock to the victim who was seated in another room. The agent received a small monetary reward of €0.05 for every shock given.

Importantly, the agent went through two different conditions. In the coerced condition, an experimenter who was present in the room instructed the agent on whether or not to deliver a shock at a given trial. In the free condition, the experimenter remained in another room, and the agent was told that they could choose whether or not to give the other participant a shock. Throughout the entire task, the agent’s brain activity was recorded using a magnetic resonance imaging (MRI) scanner.

As expected, the agents delivered more shocks during the coerced conditions than the free conditions. While in the coerced conditions, the experimenters had ordered the subjects to deliver shocks on half the trials, in the free conditions, the subjects delivered less than that with an average of 23 shocks out of 60 trials. The agents also reported feeling more “bad”, more “sorry”, and more “responsible” for administering the shocks in the free conditions, compared to the coerced conditions.

Interestingly, when obeying orders, the subjects appeared to downplay the pain they were inflicting. While administering each shock, the subjects could see a live video of the victims’ hand reacting to the shock with a visible muscle twitch. After each shock, the agents rated how painful they believed it was. The researchers found that the subjects rated the shocks as less painful when they were administered as part of an order — despite having been told at the beginning of the experiment that the shocks would be of the same intensity at every trial. “Here,” Caspar and her team emphasize, “our results would support the fact that obeying orders has such a strong influence on the perception of pain felt by others that it even impacts perceptual reports of observed shock intensity rather than only modulating how the observer feels about the pain of the other.”

The MRI results offered further evidence that obeying orders alters one’s empathy response. When researchers zeroed in on areas of the brain associated with the processing of others’ pain — areas such as the anterior cingulate cortex (ACC), dorsal striatum, middle temporal gyrus (MTG), temporoparietal junction (TPJ), and insula — they found that these areas showed reduced activation during the coerced condition. As the authors illustrate, “even in the case of a pain that is fully caused by the participants’ own actions, brain activity is altered by a lack of responsibility.”

The authors note that previous research has suggested that parts of the ACC and insula show greater activation when people are uniquely to blame for others’ pain. This falls in line with the current findings since the coerced condition was linked to reduced feelings of responsibility and reduced activation of the ACC and insula.

Overall, the findings present the unsettling possibility that following someone else’s order “relaxes our aversion against harming others” even if we are the ones carrying out the action.

The study, “Obeying orders reduces vicarious brain activation towards victims’ pain”, was authored by Emilie A. Caspar, Kalliopi Ioumpa, Christian Keysers, and Valeria Gazzola.

Mothers of Children With Autism Found to Have Significantly Different Metabolite Levels

Summary: Two to five years after birth, mothers of children on the autism spectrum have several significantly different metabolite levels than mothers of typically developing children.

Blood sample analysis showed that, two to five years after they gave birth, mothers of children with autism spectrum disorder (ASD) had several significantly different metabolite levels compared to mothers of typically developing children. That’s according to new research recently published in BMC Pediatrics by a multidisciplinary team from Rensselaer Polytechnic Institute, Arizona State University, and the Mayo Clinic.

Researchers analyzed blood samples from 30 mothers whose young children had been diagnosed with ASD and 29 mothers of typically developing children. At the time that the samples were taken, the women’s children were between 2 and 5 years old. The team found differences in several metabolite levels between the two groups of mothers.

When examined further, researchers were able to group those differences into five subgroups of correlated metabolites. While the samples analyzed were taken several years after pregnancy, these research findings raise the question of whether or not the differences in metabolites may have been present during pregnancy as well, suggesting further research is needed in this area.

Many of the variances, the researchers said, were linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. Carnitine can be produced by the body and can come from meat sources like pork or beef, but there wasn’t a correlation between mothers who ate more meat and mothers who had higher levels of carnitine.

According to Juergen Hahn, the head of the Department of Biomedical Engineering at Rensselaer and co-author on this paper, this finding suggests that the differences may be related to how carnitine is metabolized in some mothers’ bodies.

“We had multiple metabolites that were associated with the carnitine metabolism,” said Hahn, who is also a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer. “This suggests that carnitine and mothers is something that should be looked at.”

The team’s big data approach proved to be highly accurate in using a blood sample analysis to predict which group a mother belonged to, which suggests that the development of a blood test to screen for mothers who are at a higher risk of having a child with ASD may be possible.

“A blood test would not be able to tell if your child has autism or not, but it could tell if you’re at a higher risk,” Hahn said. “And the classification of higher risk, in this case, can actually be significant.”

“Based on these results, we are now conducting a new study of stored blood samples collected during pregnancy, to determine if those metabolites are also different during pregnancy,” said James Adams, a President’s Professor in the School of Engineering of Matter, Transport and Energy, and director of the Autism/Asperger’s Research Program, both at Arizona State University. Adams co-authored this paper with Hahn.

This research builds upon Hahn’s other work. He previously discovered patterns with certain metabolites in the blood of children with autism that can be used to successfully predict diagnosis. He has used this same method to investigate a mother’s risk for having a child with ASD. He and Adams have also done similar work studying children with autism who have chronic gastrointestinal issues.

Source: Rensselaer Polytechnic Institute

Original Research: Open access.
Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study” by Kathryn Hollowood-Jones, James B. Adams, Devon M. Coleman, Sivapriya Ramamoorthy, Stepan Melnyk, S. Jill James, Bryan K. Woodruff, Elena L. Pollard, Christine L. Snozek, Uwe Kruger, Joshua Chuah& Juergen Hahn. BMC Pediatrics

Personalized brain stimulation alleviates severe depression symptoms

Targeted neuromodulation tailored to individual patients’ distinctive symptoms is an increasingly common way of correcting misfiring brain circuits in people with epilepsy or Parkinson’s disease. Now, scientists at UC San Francisco’s Dolby Family Center for Mood Disorders have demonstrated a novel personalized neuromodulation approach that—at least in one patient—was able to provide relief from symptoms of severe treatment-resistant depression within minutes.

The approach is being developed specifically as a potential treatment for the significant fraction of people with debilitating depression who do not respond to existing therapies and are at high risk of suicide.

“The brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression—just like epilepsy or Parkinson’s disease—could be shifted into a healthier state by targeted stimulation,” said Katherine Scangos, MD, Ph.D., an assistant professor in the Department of Psychiatry and Behavioral Sciences and corresponding author of the new study. “Prior attempts to develop neuromodulation for depression have always applied stimulation in the same site in all patients, and on a regular schedule that fails to specifically target the pathological brain state. We know depression affects different people in very different ways, but the idea of mapping out individualized sites for neuromodulation that match a patient’s particular symptoms had not been well explored.”

In a case study published January 18, 2021 in Nature Medicine, Scangos and colleagues mapped the effects of mild stimulation of several mood-related brain sites in a patient with severe treatment-resistant depression. They found that stimulation at different sites could alleviate distinct symptoms of the brain disease—reducing anxiety, boosting energy levels, or restoring pleasure in everyday activities—and, notably, that the benefits of different stimulation sites depended on the patient’s mental state at the time.

The proof-of-concept study lays the groundwork for a major five-year clinical trial Scangos is leading, called the PRESIDIO trial, that will evaluate the effectiveness of personalized neuromodulation in 12 patients with severe treatment-resistant depression. The trial will build on the current study by identifying brain signatures that reflect individual participants’ symptoms. With this information, neuromodulation devices can be programmed to respond in real time to these faulty network states with targeted stimulation that brings patients’ brain circuits back into balance.

“We’ve developed a framework for how to go about personalizing treatment in a single individual, showing that the distinctive effects of stimulating different brain areas are reproducible, long-lasting and state-dependent,” said Andrew Krystal, MD, director of UCSF’s Dolby Center and co-senior author on the new study. “Our trial is going to be groundbreaking in that every person in the study is potentially going to get a different, personalized treatment, and we will be delivering treatment only when personalized brain signatures of a depressed brain state indicate treatment is needed.”

Depression is among the most common psychiatric disorders, affecting as many as 264 million people worldwide and leading to hundreds of thousands of deaths per year. But as many as 30 percent of patients do not respond to standard treatments such as medication or psychotherapy. Some of these individuals respond positively to electroconvulsive therapy (ECT), but stigma and side effects make ECT undesirable for many, and one in ten patients experience little benefit even from ECT.

Previous research by Edward Chang, MD, co-senior author of the new study, has demonstrated the potential of brain mapping to identify promising sites for mood-boosting brain stimulation. These studies were conducted at UCSF Epilepsy Center in patients with and without clinical depression who already had electrode arrays implanted in their brains to map seizures ahead of epilepsy surgery.

“Our prior work showed a proof of principle for targeted stimulation across brain areas to treat mood symptoms, but an outstanding question has been whether the same approach would hold true for patients with depression alone,” said Chang, who is the Joan and Sanford I. Weill Chair of the UCSF Department of Neurological Surgery and Jeanne Robertson Distinguished Professor.

In the new study, the UCSF team demonstrated the use of a similar brain-mapping approach to identify patient-specific therapeutic stimulation sites as the first phase of the PRESIDIO trial.

The team used a minimally invasive approach called stereo-EEG to place 10 intracranial electrode leads into the brain of the first patient enrolled in the trial—a 36-year-old woman who has experienced multiple episodes of severe treatment-resistant depression since childhood. The patient then spent 10 days at the UCSF Helen Diller Medical Center at Parnassus Heights while researchers systematically mapped effects of mild stimulation across a number of brain regions that prior research had shown were likely to have an effect on mood.

The researchers found that 90-second stimulation of a several different brain sites could reliably produce an array of distinctive positive emotional states, as measured by a set of clinical scales that were used to assess the patient’s mood and depression severity throughout the study. For example, after stimulation of one region, the patient reported “tingles of pleasure,” while stimulation of a second area resulted in a feeling of “neutral alertness … less cotton and cobwebs.” Stimulation of a third area—a region called orbitofrontal cortex (OFC) that had been identified in Chang’s earlier studies—produced a sensation of calm pleasure “like … reading a good book.”

The team then tested more prolonged (three- to 10-minute) stimulation of these three areas to attempt longer-lasting relief of the patient’s depression symptoms. To their surprise, they found that stimulation of each of the three sites improved her symptoms in different ways, depending on the patient’s mental state at the time of stimulation. For example, when she was experiencing anxiety, the patient reported stimulation of the OFC as positive and calming, but if the same stimulation was delivered when she was experiencing decreased energy, it worsened her mood and made her feel excessively drowsy. The opposite pattern was observed in the other two regions, where stimulation increased the patient’s arousal and energy level.

“I’ve tried literally everything, and for the first few days I was a little worried that this wasn’t going to work,” the patient recalled. “But then when they found the right spot, it was like the Pillsbury Doughboy when he gets poked in the tummy and has that involuntary giggle. I hadn’t really laughed at anything for maybe five years, but I suddenly felt a genuine sense of glee and happiness, and the world went from shades of dark gray to just—grinning.”

The researchers focused in on an area known as the ventral capsule/ventral striatum, which seemed to best address this particular patient’s primary symptoms of low energy and loss of pleasure in everyday activities.

“As they kept playing with that area, I gradually looked down at the needlework I had been doing as a way to keep my mind off negative thoughts and realized I enjoyed doing it, which was a feeling I haven’t felt for years,” she said. “It struck me so clearly in that moment that my depression wasn’t something I was doing wrong or just needed to try harder to snap out of—it really was a problem in my brain that this stimulation was able to fix. Every time they’d stimulate, I felt like, ‘I’m my old self, I could go back to work, I could do the things I want to do with my life.'”

The researchers found that the effects of stimulation could be tailored to the patient’s mood, and that positive effects lasted for hours, well beyond the 40-minute window designed into the study protocol. The patient’s symptoms also got significantly better over the course of the 10-day study, leading to a temporary remission lasting 6 weeks.

“The fact that we could eliminate this patient’s symptoms for hours with just a few minutes of targeted stimulation was remarkable to see,” Krystal said. “It emphasizes that even the most severe depression is a brain circuit disease that may just need a targeted nudge back into a healthy state. Unlike antidepressant drugs, which might not have an effect for one to three months, probably by altering brain circuits in ways we don’t understand, our hope is that this approach will be effective precisely because it only requires brief, mild stimulation when the undesired brain state we want to change is present.”

When the patient’s symptoms returned after her initial remission, the researchers proceeded to the next phase of the PRESIDIO trial—implanting a responsive neuromodulatory device called the NeuroPace RNS System. This device is widely used for seizure control in epilepsy patients, in whom it can detect signs of oncoming seizures in real time and initiate brief, targeted stimulation that cancels them out. In the PRESIDIO trial, the device instead detects signature patterns of brain activity that indicate that a participant is moving towards a highly depressed state, and then provides mild, undetectable levels of stimulation to a targeted brain region to counteract this downswing.

“We hope that providing gentle neuromodulation throughout each day will be able to prevent patients from falling into long-lasting depressive episodes,” said Scangos, who was recently awarded a 1907 Research Trailblazer Award for her work to understand depression’s neural circuitry. “The idea is that keeping neural circuit activity functioning along the correct track, the pathways that support pathological negative thought processes in depression can be unlearned.”

The NeuroPace device was implanted in June of 2020 and activated in August, and so far, the study participant has reported that her symptoms—which in the past seven years had made it impossible for her to hold a job or even drive—have almost completely vanished, despite significant life stressors like a COVID exposure, helping her parents move out of state, and caring for her mother after a fall.

“2020 was terrible for everyone, and I’ve had some particularly stressful life events, but for the first time in a long time, I feel like I can bob back up again,” she said. “I can’t tell exactly when the device turns on, but I generally feel more of a sense of clarity, an ability to look at my emotions rationally and apply the tools that I’ve worked on through psychotherapy, and that is so far from where I was before.”

In the trial’s next phase, the patient will switch between six weeks with the device turned on and six weeks with it off, without being aware of which is which, in order to assess possible placebo effects.

More information: State-dependent responses to intracranial brain stimulation in a patient with depression, Nature Medicine (2021). DOI: 10.1038/s41591-020-01175-8 , www.nature.com/articles/s41591-020-01175-8Journal information:Nature Medicine


Mice Share Each Other’s Pain and Fear

The animals adopt the emotional state of their cagemates, and the parts of the brain engaged during the process are different for pain and fear, according to a new study.

By Amanda Heidt

The ability to empathize with others stems from a long evolutionary history that includes empathy-like behaviors in animals beyond humans. Whales and primates grieve alongside members of their social groups, for example, while rodents are able to recognize and respond to the fear and pain of their neighbors. 

A study published January 8 in Science has found that the brain circuits engaged during empathetic behaviors in mice differ depending on the emotion they are experiencing. The social transmission of pain, for example, is mediated by a pathway involving the brain’s anterior cingulate cortex (ACC) and the nucleus accumbens (NAc), while empathy-based fear is dictated by projections leading from the ACC to a region called the basolateral amygdala (BLA). These results also show, for the first time, that observing a neighbor having its pain alleviated can make a mouse’s own pain more tolerable. 

“The authors were able to determine the specific inputs and outputs from the ACC to other regions of the brain, which hasn’t been done before, and show that they differ depending on what state you’re in,” Stephanie Preston, a neuroscientist and psychologist at the University of Michigan who studies empathy in humans, tells The Scientist. “This is a novel demonstration of the specific wiring that’s involved above and beyond the general idea of empathic pain and fear.”

Empathy is often studied in humans using MRI scans, during which a person must lie perfectly still within a noisy, enclosed space. As a result, “it’s much harder to get into a human brain and elucidate the mechanisms at the level of detail I think they need to be understood,” says Robert Malenka, a neuroscientist at Stanford University and the senior author on the study. 

Rodents, being social animals capable of reacting to the emotions of their neighbors, therefore provide a tractable model system for probing the neural circuits associated with empathetic behavior. A better understanding of the molecular and neurological basis of empathy is important not only for the study of social interactions in humans, but also for the development of noninvasive treatments for people with conditions that limit their ability to empathize with others, such as narcissistic personality disorder, borderline personality disorder, or psychopathy.  

To test the empathetic exchange of fear, Malenka’s team subjected a handful of mice to an electrical shock. The next day, these “bystanders” watched as a companion mouse was shocked repeatedly, causing it to freeze as part of a fight-or-flight response. A day later, when the bystander mouse was placed back into the experimental arena by itself, it too froze, supporting the idea that mice have an empathetic response to seeing others in distress.

During trials examining the same mice’s empathetic response to pain, the researchers injected 20 mice with a substance that causes inflammation. Then, a paired bystander mouse was put into the cage, and the two were able to interact with one another for an hour. Afterward, the bystander underwent a series of tests to determine its pain threshold. In each case, mice that had interacted with a cagemate registered a lower tolerance to pain for at least four hours after separation compared to a pair of control mice that interacted but neither received an inflammatory injection. 

Lastly, Malenka and his colleagues wanted to know if pain relief could be socially transferred in the same way as pain. This time, the team injected both mice with the inflammatory compound but gave one mouse morphine. Even though it had not received any morphine, the second mouse nevertheless registered a higher pain tolerance; being around an analgecized cagemate made the pain of the second mouse more bearable.  

“We think we have directly demonstrated that our mice are experiencing an empathic response,” says Malenka. “They are adopting the emotional state of another member of their species just by hanging out with that other animal for an hour or so.”

Having shown that mice can adopt the behavioral states of their neighbors, the team next used a neurological tracer and optogenetics to tease apart the individual pathways involved in each emotional state. 

For the tracer, they injected mice with a benign version of the rabies virus. “We did a clever experiment where we expressed the receptor for the rabies virus only in the neurons that were activated during the social experiments,” Malenka says. Following the path of the virus through the brain, they were able to show that the social transfer of pain and pain relief are mediated by different pathways.

The results, Malenka tells The Scientist, show that “there is some specificity to our empathic responses in terms of the brain mechanisms. Different parts of the brain are allowing us to be empathic for different experiences.” 

When the researchers used optogenetics to activate the pain circuit during the pain experiment, the response of the bystander became more pronounced, with the bystander experiencing a lower pain tolerance for 24 hours instead of four. Similarly, when they used optogenetics to turn off the link between the ACC and the NAc, the route empathic pain takes, the social transfer of the sensation stopped, demonstrating that communication between the two brain regions is necessary to prompt empathetic behaviors.

With respect to fear, the team blocked the flow of information from the ACC to the BLA and similarly mitigated a mouse’s fear response.

While mouse brains are not identical to our own, the results of this study do seem to align with some of what is known about empathy in humans, says Ewelina Knapska, a neurobiologist at the Nencki Institute of Experimental Biology in Poland. “I think it’s a very nice study because it shows the role of the cortex in controlling downstream structures in mice,” she tells The Scientist. “We know that the ACC is important in human subjects in controlling empathy-related behaviors, but here we see a very similar organization in mice. It gives us a good model to study the fine details of neuronal circuits and hope for the translatability of the research.”

At its most basic level, the results could inform new, socially mediated ways of treating pain or fear in humans, such as group therapy for those with post-traumatic stress disorder (PTSD) or changing the organization of hospital wards. Placing patients recovering from surgery in a room with others further along in their process, Preston says, could speed the healing of all. 

“Hospitals try really hard to maintain this controlled environment because they believe it’s important to the recovery of the individual,” Preston says. “We need to be aware about the distinction between controlling the environment and making it seem more scientific versus actually loosening some of these restrictions and promoting togetherness in these environments where people are trying to recover.”

Moving beyond, Malenka says that a better understanding of the pathways associated with empathy could spur conversations about drugs used to treat empathy-related disorders. While more study is needed to be sure the pathways are conserved between rodent and human, he says, this is work that is already underway. In his lab, Malenka is studying how the empathetic response of rodents is affected by MDMA, the “empathogenic drug” known as ecstasy. 

“This is not crazy stuff,” Malenka tells The Scientist, pointing out that clinical trials are currently testing the efficacy of MDMA in individuals with PTSD. “I almost can’t imagine a more important topic to study, whether you’re a psychologist or a neuroscientist, than what in our brains allows us to be empathetic and compassionate.”

Scientists Are Figuring Out Why Some People Can ‘Hear’ The Voices of The Dead


Scientists have identified the traits that may make a person more likely to claim they hear the voices of the dead.

According to new research, a predisposition to high levels of absorption in tasks, unusual auditory experiences in childhood, and a high susceptibility to auditory hallucinations all occur more strongly in self-described clairaudient mediums than the general population.

The finding could help us to better understand the upsetting auditory hallucinations that accompany mental illnesses such as schizophrenia, the researchers say.

The Spiritualist experiences of clairvoyance and clairaudience – the experience of seeing or hearing something in the absence of an external stimulus, and attributed to the spirits of the dead – is of great scientific interest, both for anthropologists studying religious and spiritual experiences, and scientists studying pathological hallucinatory experiences.

In particular, researchers would like to better understand why some people with auditory experiences report a Spiritualist experience, while others find them more distressing, and receive a mental health diagnosis.

“Spiritualists tend to report unusual auditory experiences which are positive, start early in life and which they are often then able to control,” explained psychologist Peter Moseley of Northumbria University in the UK.

“Understanding how these develop is important because it could help us understand more about distressing or non-controllable experiences of hearing voices too.”

He and his colleague psychologist Adam Powell of Durham University in the UK recruited and surveyed 65 clairaudient mediums from the UK’s Spiritualists’ National Union, and 143 members of the general population recruited through social media, to determine what differentiated Spiritualists from the general public, who don’t (usually) report hearing the voices of the dead.

Overall, 44.6 percent of the Spiritualists reported hearing voices daily, and 79 percent said the experiences were part of their daily lives. And while most reported hearing the voices inside their head, 31.7 percent reported that the voices were external, too.

The results of the survey were striking.

Compared to the general population, the Spiritualists reported much higher belief in the paranormal, and were less likely to care what other people thought of them.

The Spiritualists on the whole had their first auditory experience young, at an average age of 21.7 years, and reported a high level of absorption. That’s a term that describes total immersion in mental tasks and activities or altered states, and how effective the individual is at tuning out the world around them.

In addition, they reported that they were more prone to hallucination-like experiences. The researchers noted that they hadn’t usually heard of Spiritualism prior to their experiences; rather, they had come across it while looking for answers.

In the general population, high levels of absorption were also strongly correlated with belief in the paranormal – but little or no susceptibility to auditory hallucinations. And in both groups, there were no differences in the levels of belief in the paranormal and susceptibility to visual hallucinations.

These results, the researchers say, suggest that experiencing the ‘voices of the dead’ is therefore unlikely to be a result of peer pressure, a positive social context, or suggestibility due to belief in the paranormal. Instead, these individuals adopt Spiritualism because it aligns with their experience and is personally meaningful to them.

“Our findings say a lot about ‘learning and yearning’. For our participants, the tenets of Spiritualism seem to make sense of both extraordinary childhood experiences as well as the frequent auditory phenomena they experience as practising mediums,” Powell said.

“But all of those experiences may result more from having certain tendencies or early abilities than from simply believing in the possibility of contacting the dead if one tries hard enough.”

Future research, they concluded, should explore a variety of cultural context to better understand the relationship between absorption, belief, and the strange, spiritual experience of ghosts whispering in one’s ear.

The research has been published in Mental Health, Religion and Culture.


Scientists Just Discovered 3 New Kinds of Carnivorous Sponge in The Deep Ocean


Even though we know the deep sea is weird, ‘carnivorous sea sponges’ still sound like something from a sci-fi movie. And yet, researchers just announced the discovery of three new such species off the coast of Australia.

Go a few hundred metres deep into the ocean, and it starts to look like you’re in a whole new world: From a creature that looks like a sea star crossed with an octopus, to shark-devouring fish, to carnivorous sponges we’ve never seen before.

“It just goes to show how much of our deep oceans are yet to be explored – these particular sponges are quite unique in that they are only found in this particular region of The Great Australian Bight – a region that was slated for deep sea oil exploration,” said one of the researchers, Queensland Museum Sessile Marine Invertebrates Collection manager Merrick Ekins.

Typically, sea sponges are multicellular filter feeders – they have holey tissues for flowing water, from which their cells extract oxygen and food. They’re pretty simple creatures, with no nervous, digestive, or circulatory system, but have existed in some form for over 500 million years.

But carnivorous sponges are a bit different. Some carnivorous sponges still use the water flow system, while others (like the three newly discovered species) have lost this ability altogether, and nab small crustaceans and other prey using filaments or hooks.

The researchers in this study found three new species of carnivorous sponges – Nullarbora heptaxiaAbyssocladia oxyasters and Lycopodina hystrix, which are also all new genera, as well as a closely related species of sponge that isn’t carnivorous, Guitarra davidconryi. All these species were found at depths of between 163 and over 3,000 metres (535 to 9,842 feet) deep.

“Here we report on an additional four new species of sponges discovered from the Great Australian Bight, South Australia. This area has recently been surveyed, using a Smith-McIntyre Grab and a Remotely Operated Vehicle (ROV) to photograph and harvest the marine biota,” the researchers write in their new paper.

“These new species are the first recorded carnivorous species from South Australia and increase the number of species recorded from around Australia to 25.”

The sponges are also prettier than you would imagine, looking a little like flowers with their spiky protrusions, but not a lot like sponges. 

Carnivorous sponges are having a bit of a moment. We’ve known about them since 1995, but many more have recently been discovered around the world.

“Over the past two decades, our knowledge of carnivorous sponge diversity has almost doubled,” the same team explains in an earlier paper, where they described their discovery of 17 new species of carnivorous sponges.

“[This is] due in part to rapid advances in deep sea technology including ROVs and submersibles able to photograph and harvest carnivorous sponges intact, and also to the herculean efforts of a number of contemporary taxonomists redescribing many of the older species described in the 19th and 20th centuries.”

Nearly every species of carnivorous sponge found in Australia was discovered during a CSIRO RV Investigator Voyage in 2017, showing just how important these deep-sea investigations are.

With the bottom of the ocean still mostly unexplored, we imagine we’ll see plenty more species of carnivorous sponges, and other weird and wonderful sea creatures. 

The research has been published in Zootaxa.


Disagreement creates cognitive disharmony

By Bill Hathaway

Yale researchers have devised a way to peer into the brains of two people simultaneously while are engaged in discussion. What they found will not surprise anyone who has found themselves arguing about politics or social issues.

When two people agree, their brains exhibit a calm synchronicity of activity focused on sensory areas of the brain. When they disagree, however, many other regions of the brain involved in higher cognitive functions become mobilized as each individual combats the other’s argument, a Yale-led research team reports Jan. 13 in the journal Frontiers in Human Neuroscience.

“Our entire brain is a social processing network,” said senior author Joy Hirsch, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of comparative medicine and neuroscience. “However, it just takes a lot more brain real estate to disagree than to agree.”

For the study, the researchers from Yale and the University College London recruited 38 adults who were asked to say whether they agreed or disagreed with a series of statements such as “same-sex marriage is a civil right” or “marijuana should be legalized.”  After matching up pairs based on their responses the researchers used an imaging technology called functional near-infrared spectroscopy to record their brain activity while they engaged in face-to-face discussions.

When the people were in agreement, brain activity was harmonious and tended to be concentrated on sensory areas of the brain such as the visual system, presumably in response to social cues from their partner. However, during disputes these areas of the brain were less active. Meanwhile, activity increased in the brain’s frontal lobes, home of higher order executive functions.

“There is a synchronicity between the brains when we agree,” Hirsch said. “But when we disagree, the neural coupling disconnects.”

Understanding how our brains function while disagreeing or agreeing is particularly important in a polarized political environment, Hirsch noted.

In discord, she said, two brains engage many emotional and cognitive resources “like a symphony orchestra playing different music.” In agreement, there “is less cognitive engagement and more social interaction between brains of the talkers, similar to a musical duet.” 

The lead investigator of the paper is Alex Salama-Manteau, a former graduate student of economics at Yale and now a data scientist at Airbnb. Mark Tiede, a research scientist at the Haskins Laboratory at Yale, is second author of the paper.