Category Archives: Neuroscience

Neuroscience

Implant Shows Promise in Restoring Cognitive Function After Brain Injury – Neuroscience News

Summary: A groundbreaking study successfully restored cognitive function in patients with lasting impairments from traumatic brain injuries using deep-brain-stimulation devices.

This innovative technique targets the central lateral nucleus in the thalamus to reactivate neural pathways associated with attention and arousal.

The studys participants, who had suffered moderate to severe brain injuries, showed remarkable improvements in mental processing speed, concentration, and daily life activities.

These findings offer new hope for individuals struggling with the long-term effects of traumatic brain injuries.

Key Facts:

Source: Stanford

In 2001, Gina Arata was in her final semester of college, planning to apply to law school, when she suffered a traumatic brain injury in a car accident. The injury so compromised her ability to focus she struggled in a job sorting mail.

I couldnt remember anything, said Arata, who lives in Modesto with her parents. My left foot dropped, so Id trip over things all the time. I was always in car accidents. And I had no filter Id get pissed off really easily.

Her parents learned about research being conducted at Stanford Medicine and reached out; Arata was accepted as a participant. In 2018, physicians surgically implanted a device deep inside her brain, then carefully calibrated the devices electrical activity to stimulate the networks the injury had subdued.

She noticed the difference immediately: When she was asked to list items in the produce aisle of a grocery store, she could rattle off fruits and vegetables. Then a researcher turned the device off, and she couldnt name any.

Since the implant I havent had any speeding tickets, Arata said. I dont trip anymore. I can remember how much money is in my bank account. I wasnt able to read, but after the implant I bought a book,Where the Crawdads Sing, and loved it and remembered it. And I dont have that quick temper.

For Arata and four others, the experimental deep-brain-stimulation device restored, to different degrees, the cognitive abilities they had lost to brain injuries years before. The new technique, developed by Stanford Medicine researchers and collaborators from other institutions, is the first to show promise against the long-lasting impairments from moderate to severe traumatic brain injuries.

The results of the clinical trial will be published Dec. 4 inNature Medicine.

Dimmed lights

More than 5 million Americans live with the lasting effects of moderate to severe traumatic brain injury difficulty focusing, remembering and making decisions. Though many recover enough to live independently, their impairments prevent them from returning to school or work and from resuming their social lives.

In general, theres very little in the way of treatment for these patients, saidJaimie Henderson, MD, professor of neurosurgery and co-senior author of the study.

But the fact that these patients had emerged from comas and recovered a fair amount of cognitive function suggested that the brain systems that support attention and arousal the ability to stay awake, pay attention to a conversation, focus on a task were relatively preserved.

These systems connect the thalamus, a relay station deep inside the brain, to points throughout the cortex, the brains outer layer, which control higher cognitive functions.

In these patients, those pathways are largely intact, but everything has been down-regulated, said Henderson, the John and Jene Blume-Robert and Ruth Halperin Professor. Its as if the lights had been dimmed and there just wasnt enough electricity to turn them back up.

In particular, an area of the thalamus called the central lateral nucleus acts as a hub that regulates many aspects of consciousness.

The central lateral nucleus is optimized to drive things broadly, but its vulnerability is that if you have a multifocal injury, it tends to take a greater hit because a hit can come from almost anywhere in the brain, saidNicholas Schiff, MD, a professor at Weill Cornell Medicine and co-senior author of the study.

The researchers hoped that precise electrical stimulation of the central lateral nucleus and its connections could reactivate these pathways, turning the lights back up.

Precise placement

In the trial, the researchers recruited five participants who had lasting cognitive impairments more than two years after moderate to severe traumatic brain injury. They were aged 22 to 60, with injuries sustained three to 18 years earlier.

The challenge was placing the stimulation device in exactly the right area, which varied from person to person. Each brain is shaped differently to begin with, and the injuries had led to further modifications.

Thats why we developed a number of tools to better define what that area was, Henderson said. The researchers created a virtual model of each brain that allowed them to pinpoint the location and level of stimulation that would activate the central lateral nucleus.

Guided by these models, Henderson surgically implanted the devices in the five participants.

Its important to target the area precisely, he said. If youre even a few millimeters off target, youre outside the effective zone.

A pioneering moment

After a two-week titration phase to optimize the stimulation, the participants spent 90 days with the device turned on for 12 hours a day.

Their progress was measured by a standard test of mental processing speed, called the trail-making test, which involves drawing lines connecting a jumble of letters and numbers.

Its a very sensitive test of exactly the things that were looking at: the ability to focus, concentrate and plan, and to do this in a way that is sensitive to time, Henderson said.

At the end of the 90-day treatment period, the participants had improved their speeds on the test, on average, by 32%, far exceeding the 10% the researchers had aimed for.

The only surprising thing is it worked the way we predicted it would, which is not always a given, Henderson said.

For the participants and their families, the improvements were apparent in their daily lives. They resumed activities that had seemed impossible reading books, watching TV shows, playing video games or finishing a homework assignment. They felt less fatigued and could get through the day without napping.

The therapy was so effective the researchers had trouble completing the last part of their study. They had planned a blinded withdrawal phase, in which half the participants would be randomly selected to have their devices turned off.

Two of the patients declined, unwilling to take that chance. Of the three who participated in the withdrawal phase, one was randomized to have their device turned off. After three weeks without stimulation, that participant performed 34% slower on the trail-making test.

The clinical trial is the first to target this region of the brain in patients with moderate to severe traumatic brain injury, and it offers hope for many who have plateaued in their recovery.

This is a pioneering moment, Schiff said. Our goal now is to try to take the systematic steps to make this a therapy. This is enough of a signal for us to make every effort.

Researchers from Weill Cornell Medicine, Spaulding Rehabilitation Hospital in Boston, Harvard Medical School, the University of Utah, the University of Florida, Vanderbilt University, the University of Washington, the University of Bordeaux and the Cleveland Clinic also contributed to the study.

Funding: The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic.

Author: Nina Bai Source: Stanford Contact: Nina Bai Stanford Image: The image is credited to Neuroscience News

Original Research: Closed access. Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study byJaimie Henderson et al. Nature Medicine

Abstract

Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.

Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.

All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.

CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.

ClinicalTrials.gov identifier:NCT02881151.

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Implant Shows Promise in Restoring Cognitive Function After Brain Injury - Neuroscience News

Neuroscience

New neuroscience research upends traditional theories of early language learning in babies – PsyPost

New research suggests that babies primarily learn languages through rhythmic rather than phonetic information in their initial months. This finding challenges the conventional understanding of early language acquisition and emphasizes the significance of sing-song speech, like nursery rhymes, for babies. The study was published in Nature Communications.

Traditional theories have posited that phonetic information, the smallest sound elements of speech, forms the foundation of language learning. In language development, acquiring phonetic information means learning to produce and understand these different sounds, recognizing how they form words and convey meaning.

Infants were believed to learn these individual sound elements to construct words. However, recent findings from the University of Cambridge and Trinity College Dublin suggest a different approach to understanding how babies learn languages.

The new study was motivated by the desire to better understand how infants process speech in their first year of life, specifically focusing on the neural encoding of phonetic categories in continuous natural speech. Previous research in this field predominantly used behavioral methods and discrete stimuli, which limited insights into how infants perceive and process continuous speech. These traditional methods were often constrained to simple listening scenarios and few phonetic contrasts, which didnt fully represent natural speech conditions.

To address these gaps, the researchers used neural tracking measures to assess the neural encoding of the full phonetic feature inventory of continuous speech. This method allowed them to explore how infants brains process acoustic and phonetic information in a more naturalistic listening environment.

The study involved a group of 50 infants, monitored at four, seven, and eleven months of age. Each baby was full-term and without any diagnosed developmental disorders. The research team also included 22 adult participants for comparison, though data from five were later excluded.

In a carefully controlled environment, the infant participants were seated in a highchair, a meter away from their caregiver, inside a sound-proof chamber. The adults sat similarly in a normal chair. Each participant, whether infant or adult, was presented with eighteen nursery rhymes played via video recordings. These rhymes, sung or chanted by a native English speaker, were selected carefully to cover a range of phonetic features. The sounds were delivered at a consistent volume.

To capture how the infants brains responded to these nursery rhymes, the researchers used a method called electroencephalography (EEG), which records patterns of brain activity. This technique is non-invasive and involved placing a soft cap with sensors on the infants heads to measure their brainwaves.

The brainwave data was then analyzed using a sophisticated algorithm to decode the phonological information allowing them to create a readout of how the infants brains were processing the different sounds in the nursery rhymes. This technique is significant as it moved beyond the traditional method of just comparing reactions to individual sounds or syllables, allowing a more comprehensive understanding of how continuous speech is processed.

Contrary to what was previously thought, the researchers found that infants do not process individual speech sounds reliably until they are about seven months old. Even at eleven months, when many babies start to say their first words, the processing of these sounds is still sparse.

Furthermore, the study discovered that phonetic encoding in babies emerged gradually over the first year. The read out of brain activity showed that the processing of speech sounds in infants started with simpler sounds like labial and nasal ones, and this processing became more adult-like as they grew older.

Our research shows that the individual sounds of speech are not processed reliably until around seven months, even though most infants can recognize familiar words like bottle by this point, said study co-author Usha Goswami, a professor at the University of Cambridge. From then individual speech sounds are still added in very slowly too slowly to form the basis of language.

The current study is part of the BabyRhythm project, which is led by Goswami.

First author Giovanni Di Liberto, a professor at Trinity College Dublin, added: This is the first evidence we have of how brain activity relates to phonetic information changes over time in response to continuous speech.

The researchers propose that rhythmic speech the pattern of stress and intonation in spoken language is crucial for language learning in infants. They found that rhythmic speech information was processed by babies as early as two months old, and this processing predicted later language outcomes.

The findings challenge traditional theories of language acquisition that emphasize the rapid learning of phonetic elements. Instead, the study suggests that the individual sounds of speech are not processed reliably until around seven months, and the addition of these sounds into language is a gradual process.

The study underscores the importance of parents talking and singing to their babies, using rhythmic speech patterns such as those found in nursery rhymes. This could significantly influence language outcomes, as rhythmic information serves as a framework for adding phonetic information.

We believe that speech rhythm information is the hidden glue underpinning the development of a well-functioning language system, said Goswami. Infants can use rhythmic information like a scaffold or skeleton to add phonetic information on to. For example, they might learn that the rhythm pattern of English words is typically strong-weak, as in daddy or mummy, with the stress on the first syllable. They can use this rhythm pattern to guess where one word ends and another begins when listening to natural speech.

Parents should talk and sing to their babies as much as possible or use infant directed speech like nursery rhymes because it will make a difference to language outcome, she added.

While this study offers valuable insights into infant language development, its important to recognize its limitations. The research focused on a specific demographic full-term infants without developmental disorders, mainly from a monolingual English-speaking environment. Future research could look into how infants from different linguistic and cultural backgrounds, or those with developmental challenges, process speech.

Additionally, the study opens up new avenues for exploring how early speech processing relates to language disorders, such as dyslexia. This could be particularly significant in understanding and potentially intervening in these conditions early in life.

The study, Emergence of the cortical encoding of phonetic features in the first year of life, was authored by Giovanni M. Di Liberto, AdamAttaheri, Giorgia Cantisani, Richard B. Reilly, ineN Choisdealbha, SineadRocha, PerrineBrusini, and Usha Goswami.

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New neuroscience research upends traditional theories of early language learning in babies - PsyPost

Neuroscience

Link Between Childhood Adversity and Muscle Dysmorphia in Youth – Neuroscience News

Summary: A new study reveals a significant association between adverse childhood experiences (ACEs) and symptoms of muscle dysmorphia in adolescents and young adults.

The research highlights how ACEs, such as domestic violence and emotional abuse, can lead to the pathological pursuit of muscularity as a coping mechanism. The study found that boys and young men who experienced five or more ACEs were particularly at risk for muscle dysmorphia symptoms.

The findings emphasize the importance of recognizing and addressing the impact of childhood trauma on mental health and body image.

Key Facts:

Source: University of Toronto

A new study published inClinical Social Work Journalfound that adolescents and young adults who experienced adverse childhood experiences (ACEs) before the age of 18 were significantly more likely to experience symptoms of muscle dysmorphia.

With previous research showing that more than half of North American children and adolescents experience at least one adverse childhood experience in their lifetime, these new findings highlight the need for greater awareness of how adverse experiences in childhood (such as domestic violence, emotional abuse, and sexual abuse) and muscle dysmorphia (the pathological pursuit of muscularity) are linked.

Those who experience adverse childhood experiences may engage in the pursuit of muscularity to compensate for experiences where they once felt inferior, small, and at risk, as well as to protect against future victimization, says lead author Kyle T. Ganson, PhD, MSW, an assistant professor at the University of Torontos Factor-Inwentash Faculty of Social Work.

The experience of adverse childhood experiences may also increase body dissatisfaction, specifically muscle dissatisfaction, which is a key feature of muscle dysmorphia.

Previous studies have shown that adverse experiences in childhood can lead to harmful health effects. While prior research has demonstrated that adverse childhood experiences are highly common in people with eating disorders and body dysmorphic disorder, few studies have looked at the association between adverse childhood experiences and muscle dysmorphia.

The studys researchers analyzed data from over 900 adolescents and young adults who participated in the Canadian Study of Adolescent Health Behaviors. In total, 16% of participants who experienced five or more adverse childhood experiences were at clinical risk for muscle dysmorphia, underscoring the significant traumatic effects that such experiences can have on mental health and well-being.

Importantly, our study found that gender was an important factor in the relationship between adverse childhood experiences and muscle dysmorphia symptoms, says Ganson.

Boys and young men in the study who have experienced five or more adverse childhood experiences had significantly greater muscle dysmorphia symptoms when compared to girls and young women.

The authors note that boys and young men who experience adverse childhood experiences may feel that their masculinity was threatened from these experiences. Therefore, they engage in the pursuit of muscularity to demonstrate their adherence to masculine gender norms such as dominance, aggression, and power.

It is important for health care professionals to assess for symptoms of muscle dysmorphia, including muscle dissatisfaction and functional impairment related to exercise routines and body image, among young people who have experienced adverse childhood experiences, particularly boys and young men, concludes Ganson.

Author: Dale Duncan Source: University of Toronto Contact: Dale Duncan University of Toronto Image: The image is credited to Neuroscience News

Original Research: Closed access. Adverse Childhood Experiences and Muscle Dysmorphia Symptomatology: Findings from a Sample of Canadian Adolescents and Young Adults by Kyle T. Ganson et al. Clinical Social Work Journal

Abstract

Adverse Childhood Experiences and Muscle Dysmorphia Symptomatology: Findings from a Sample of Canadian Adolescents and Young Adults

Adverse childhood experiences (ACEs) are relatively common among the general population and have been shown to be associated with eating disorders and body dysmorphic disorder. It remains relatively unknown whether ACEs are associated with muscle dysmorphia.

The aim of this study was to investigate the association between ACEs and muscle dysmorphia symptomatology among a sample of Canadian adolescents and young adults. A community sample of 912 adolescents and young adults ages 1630 years across Canada participated in this study.

Participants completed a 15-item measure of ACEs (categorized to 0, 1, 2, 3, 4, and 5 or more) and the Muscle Dysmorphic Disorder Inventory. Multiple linear regression analyses were utilized to determine the association between the number of ACEs experienced and muscle dysmorphia symptomatology.

Participants who experienced five or more ACEs, compared to those who had experienced no ACEs, had more symptoms of muscle dysmorphia, as well as more symptoms related to Appearance Intolerance and Functional Impairment.

There was no association between ACEs and Drive for Size symptoms. Participants who experienced five or more ACEs (16.1%), compared to 10.6% who experienced no ACEs, were at clinical risk for muscle dysmorphia (p=.018).

Experiencing ACEs, particularly five or more, was significantly associated with muscle dysmorphia symptomatology, expanding prior research on eating disorders and body dysmorphic disorder. Social workers should consider screening for symptoms of muscle dysmorphia among adolescents and young adults who experience ACEs.

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Link Between Childhood Adversity and Muscle Dysmorphia in Youth - Neuroscience News

Neuroscience

The Role of Protein Misfolding in Neurodegenerative Diseases – Neuroscience News

Summary: Neurodegenerative diseases share a common factor: protein misfolding and deposits in the brain. Misfolded proteins can lead to toxic activity or the loss of the proteins physiological function, causing damage to neurons.

Recent research explores the cross-seeding phenomenon, where misfolded proteins in one disease can induce the aggregation of others. The study specifically focuses on the interaction between the prion protein and TDP-43, shedding light on how they collaborate to impact neurodegenerative diseases.

Key Facts:

Source: RUB

The causes of neurodegenerative diseases such as Alzheimers disease, Parkinsons disease, frontotemporal dementia and prion diseases can be many and varied. But there is a common denominator, namely protein misfolding and the occurrence of protein deposits in the brain.

Various approaches and models have shown that misfolded proteins play a crucial role in the disease process, says Jrg Tatzelt.

Still, theres an ongoing debate about the nature of the harmful protein species and how misfolded proteins selectively damage specific neurons.

Studies on genes associated with pathologies have revealed two basic mechanisms by which misfolded proteins can lead to neurodegeneration: Firstly, misfolding can cause the protein to acquire toxic activity. Secondly, the misfolding can lead to a loss of the physiological function of the protein, which impairs important physiological processes in the cell.

The assumption used to be that every neurodegenerative disease was characterized by the misfolding of a specific protein, explains Jrg Tatzelt.

However, it has since been shown that misfolded proteins that are produced more frequently in one disease can also induce the aggregation of other proteins, a mechanism referred to as cross-seeding.

The prion protein and TDP-43

TDP-43 (TAR DNA-binding protein 43) is a protein that helps to translate genetic information into specific proteins. It thus helps to maintain the protein balance in nerve cells. The clumping of TDP-43 in the cell is a characteristic feature in the brains of patients suffering from amyotrophic lateral sclerosis or frontotemporal dementia.

Misfolding of the prion protein triggers prion diseases such as Creutzfeldt-Jakob disease. All research findings to date indicate that the misfolded prion protein acquires toxic activity. However, the exact mechanisms by which disease-associated prion proteins trigger the death of nerve cells are only partially understood.

TDP-43 loses its physiological function through PrP-mediated cross-seeding

Using in vitro and cell culture approaches, animal models and brain samples from patients with Creutzfeldt-Jakob disease, the researchers showed that misfolded prion proteins can trigger the clumping and inactivation of TDP-43.

The prion proteins interact with TDP-43 in vitro and in cells, thus inducing the formation of TDP aggregates in the cell. As a result, TDP-43-dependent splicing activity in the cell nucleus is significantly reduced, leading to altered protein expression.

Prion protein and TDP-43 are partners in crime in neurodegenerative diseases, so to speak, says Jrg Tatzelt.

An analysis of brain samples showed that in some Creutzfeld-Jacob patients, TDP-43 aggregates were found alongside the prion protein deposits. This study has revealed a new mechanism of how disease-associated prion proteins can affect physiological signaling pathways through cross-seeding.

Author: Meike Driessen Source: RUB Contact: Meike Driessen RUB Image: The image is credited to Neuroscience News

Original Research: Closed access. Cross-Seeding by Prion Protein Inactivates TDP-43 by Jrg Tatzelt et al. Brain

Abstract

Cross-Seeding by Prion Protein Inactivates TDP-43

A common pathological denominator of various neurodegenerative diseases is the accumulation of protein aggregates. Neurotoxic effects are caused by a loss of the physiological activity of the aggregating protein and/or a gain of toxic function of the misfolded protein conformers. In transmissible spongiform encephalopathies or prion diseases, neurodegeneration is caused by aberrantly folded isoforms of the prion protein (PrP).

However, it is poorly understood how pathogenic PrP conformers interfere with neuronal viability. Employingin vitroapproaches, cell culture, animal models and patients brain samples, we show that misfolded PrP can induce aggregation and inactivation of TAR DNA-binding protein-43 (TDP-43).

Purified PrP aggregates interact with TDP-43in vitroand in cells and induce the conversion of soluble TDP-43 into non-dynamic protein assemblies. Similarly, mislocalized PrP conformers in the cytosol bind to and sequester TDP-43 in cytosolic aggregates.

As a consequence, TDP-43-dependent splicing activity in the nucleus is significantly decreased, leading to altered protein expression in cells with cytosolic PrP aggregates. Finally, we present evidence for cytosolic TDP-43 aggregates in neurons of transgenic flies expressing mammalian PrP and CreutzfeldtJakob disease patients.

Our study identified a novel mechanism of how aberrant PrP conformers impair physiological pathways by cross-seeding.

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The Role of Protein Misfolding in Neurodegenerative Diseases - Neuroscience News

Neuroscience

Anthrobots: Tiny Biobots From Human Cells Heal Neurons – Neuroscience News

Summary: Researchers developed Anthrobots, microscopic biological robots made from human tracheal cells, demonstrating potential in healing and regenerative medicine.

These self-assembling multicellular robots, ranging from hair-width to pencil-point size, show remarkable healing effects, particularly in neuron growth across damaged areas in lab conditions.

Building on earlier Xenobot research, this study reveals that Anthrobots can be created from adult human cells without genetic modification, offering a new approach to patient-specific therapeutic tools.

Key Facts:

Source: Tufts University

Researchers at Tufts University and Harvard Universitys Wyss Institute have created tiny biological robots that they call Anthrobots from human tracheal cells that can move across a surface and have been found to encourage the growth of neurons across a region of damage in a lab dish.

The multicellular robots, ranging in size from the width of a human hair to the point of a sharpened pencil, were made to self-assemble and shown to have a remarkable healing effect on other cells. The discovery is a starting point for the researchers vision to use patient-derived biobots as new therapeutic tools for regeneration, healing, and treatment of disease.

The work follows from earlier research in the laboratories of Michael Levin, Vannevar Bush Professor of Biology at Tufts UniversitySchool of Arts & Sciences, and Josh Bongard at the University of Vermont in which they created multicellular biological robots from frog embryo cells calledXenobots, capable of navigating passageways, collecting material,recording information, healing themselves from injury, and evenreplicating for a few cycleson their own.

At the time, researchers did not know if these capabilities were dependent on their being derived from an amphibian embryo, or if biobots could be constructed from cells of other species.

In the current study, published inAdvanced Science, Levin, along with PhD student Gizem Gumuskaya discovered that bots can in fact be created from adult human cells without any genetic modification and they are demonstrating some capabilities beyond what was observed with the Xenobots.

The discovery starts to answer a broader question that the lab has posedwhat are the rules that govern how cells assemble and work together in the body, and can the cells be taken out of their natural context and recombined into different body plans to carry out other functions by design?

In this case, researchers gave human cells, after decades of quiet life in the trachea, a chance to reboot and find ways of creating new structures and tasks.

We wanted to probe what cells can do besides create default features in the body, said Gumuskaya, who earned a degree in architecture before coming into biology.

By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.

The researchers found that not only could the cells create new multicellular shapes, but they could move in different ways over a surface of human neurons grown in a lab dish and encourage new growth to fill in gaps caused by scratching the layer of cells.

Exactly how the Anthrobots encourage growth of neurons is not yet clear, but the researchers confirmed that neurons grew under the area covered by a clustered assembly of Anthrobots, which they called a superbot.

The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body, said Levin, who also serves as the director of the Allen Discovery Center at Tufts and is an associate faculty member of the Wyss Institute. It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage, said Levin.

Were now looking at how the healing mechanism works, and asking what else these constructs can do.

The advantages of using human cells include the ability to construct bots from a patients own cells to perform therapeutic work without the risk of triggering an immune response or requiring immunosuppressants. They only last a few weeks before breaking down, and so can easily be re-absorbed into the body after their work is done.

In addition, outside of the body, Anthrobots can only survive in very specific laboratory conditions, and there is no risk of exposure or unintended spread outside the lab. Likewise, they do not reproduce, and they have no genetic edits, additions or deletions, so there is no risk of their evolving beyond existing safeguards.

How Are Anthrobots Made?

Each Anthrobot starts out as a single cell, derived from an adult donor. The cells come from the surface of the trachea and are covered with hairlike projections called cilia that wave back and forth. The cilia help the tracheal cells push out tiny particles that find their way into air passages of the lung.

We all experience the work of ciliated cells when we take the final step of expelling the particles and excess fluid by coughing or clearing our throats. Earlier studies by others had shown that when the cells are grown in the lab, they spontaneously form tiny multicellular spheres called organoids.

The researchers developed growth conditions that encouraged the cilia to face outward on organoids. Within a few days they started moving around, driven by the cilia acting like oars. They noted different shapes and types of movement the first. important feature observed of the biorobotics platform.

Levin says that if other features could be added to the Anthrobots (for example, contributed by different cells), they could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.

The team, with the help of Simon Garnier at the New Jersey Institute of Technology, characterized the different types of Anthrobots that were produced. They observed that bots fell into a few discrete categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the point of a sharpened pencil), filling an important niche between nanotechnology and larger engineered devices.

Some were spherical and fully covered in cilia, and some were irregular or football shaped with more patchy coverage of cilia, or just covered with cilia on one side. They traveled in straight lines, moved in tight circles, combined those movements, or just sat around and wiggled. The spherical ones fully covered with cilia tended to be wigglers.

The Anthrobots with cilia distributed unevenly tended to move forward for longer stretches in straight or curved paths. They usually survived about 45-60 days in laboratory conditions before they naturally biodegraded.

Anthrobots self-assemble in the lab dish, said Gumuskaya, who created the Anthrobots. Unlike Xenobots, they dont require tweezers or scalpels to give them shape, and we can use adult cells even cells from elderly patients instead of embryonic cells. Its fully scalablewe can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.

LittleHealers

Because Levin and Gumuskaya ultimately plan to make Anthrobots with therapeutic applications, they created a lab test to see how the bots might heal wounds. The model involved growing a two-dimensional layer of human neurons, and simply by scratching the layer with a thin metal rod, they created an open wound devoid of cells.

To ensure the gap would be exposed to a dense concentration of Anthrobots, they created superbots a cluster that naturally forms when the Anthrobots are confined to a small space. The superbots were made up primarily of circlers and wigglers, so they would not wander too far away from the open wound.

Although it might be expected that genetic modifications of Anthrobot cells would be needed to help the bots encourage neural growth, surprisingly the unmodified Anthrobots triggered substantial regrowth, creating a bridge of neurons as thick as the rest of the healthy cells on the plate.

Neurons did not grow in the wound where Anthrobots were absent. At least in the simplified 2D world of the lab dish, the Anthrobot assemblies encouraged efficient healing of live neural tissue.

According to the researchers, further development of the bots could lead to other applications, including clearing plaque buildup in the arteries of atherosclerosis patients, repairing spinal cord or retinal nerve damage, recognizing bacteria or cancer cells, or delivering drugs to targeted tissues. The Anthrobots could in theory assist in healing tissues, while also laying down pro-regenerative drugs.

Making New Blueprints, Restoring Old Ones

Gumuskaya explained that cells have the innate ability to self-assemble into larger structures in certain fundamental ways.

The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move, Gumuskaya said.

Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functionsdifferent than those found in nature.

Taking advantage of the inherently flexible rules of cellular assembly helps the scientists construct the bots, but it can also help them understand how natural body plans assemble, how the genome and environment work together to create tissues, organs, and limbs, and how to restore them withregenerative treatments.

Author: Mike Silver Source: Tufts University Contact: Mike Silver Tufts University Image: The image is credited to Gizem Gumuskaya, Tufts University

Original Research: Open access. Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells by Michael Levin et al. Advanced Science

Abstract

Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells

Fundamental knowledge gaps exist about the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from genetically wild-type cells.

Here anthrobots are introduced, a spheroid-shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500microns and cilia-powered locomotive abilities.

Each Anthrobot begins as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after being cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat.

Anthrobots exhibit diverse behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 550micronss1. The anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity.

Anthrobots can assume morphologies with fully polarized or wholly ciliated bodies and spherical or ellipsoidal shapes, each related to a distinct movement type. Anthrobots are found to be capable of traversing, andinducing rapid repair of scratches in, cultured human neural cell sheets in vitro.

By controlling microenvironmental cues in bulk, novel structures, with new and unexpected behavior and biomedically-relevant capabilities, can be discovered in morphogenetic processes without direct genetic editing or manual sculpting.

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Anthrobots: Tiny Biobots From Human Cells Heal Neurons - Neuroscience News

Neuroscience

Neuroscience and Neurology: New Insights into Neurodegenerative Diseases – Medriva

Recent findings in neuroscience and neurology have started to shed light on the intricate connections between personality traits, dementia diagnoses, Parkinsons disease, and multiple sclerosis. These understandings not only contribute to the scientific communitys growing knowledge of these complex conditions but also potentially pave the way for innovative treatment options.

A recent meta-analysis revealed that personality traits are strong predictors of dementia diagnoses. However, the association between these traits and neuropathology at autopsy was not consistently found. This suggests that while personality traits may help predict the risk of dementia, they may not directly correlate with the physical manifestations of the disease in the brain.

Another significant finding is that neuronally derived extracellular vesicle-associated alpha-synuclein in serum correctly identified 80% of at-risk individuals who phenoconverted to Parkinsons disease and related dementia. This discovery suggests that this biomarker could be instrumental in identifying individuals at risk of developing Parkinsons disease and related dementia.

Groundbreaking treatment approaches are also being explored. High-dose nicotinamide riboside, a form of vitamin B3, showed promise in easing Parkinsons motor symptoms in a phase I trial. Additionally, a phase I study demonstrated the tolerability of injecting allogeneic neural stem cells into the brains of people with secondary progressive multiple sclerosis, suggesting potential new therapeutic approaches for these neurodegenerative diseases.

Another area of recent research has focused on the link between blood-based biomarkers of amyloid, tau, and neurodegeneration and domain-specific neuropsychological performance in women with and without HIV. The results could have significant implications for understanding cognitive impairment in both the general population and those living with HIV.

The role of the TREM2 protein in neurodegeneration has also been a focus of recent research. Specifically, a mutation in this protein may promote synapse loss in mice, contributing to cognitive decline. Furthermore, salty immune cells surrounding the brain were associated with hypertension-induced dementia in mice, suggesting a possible link between dietary salt intake, hypertension, and dementia.

Finally, a Norwegian study found a moderate association between objectively measured hearing impairment and dementia in people aged 70 to 85. This correlation underlines the importance of early detection and intervention in hearing impairment to potentially reduce the risk of dementia.

In conclusion, these developments in neuroscience and neurology are expanding our understanding of neurodegenerative diseases and offering new avenues for potential treatments. The ongoing research in this field continues to bring hope for those affected by these conditions and their families.

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Neuroscience and Neurology: New Insights into Neurodegenerative Diseases - Medriva

Neuroscience

How Imagination Fuels Empathy and Prosocial Behavior – Neuroscience News

Summary: A new study highlights the significant role of imagination in evoking empathy and driving prosocial behavior. While empathy is multifaceted, this research focuses on two aspects: personal distress and compassionate concern.

The study reveals that vividly imagining someone elses problems increases personal distress, motivating individuals to offer help.

These findings break new ground in understanding the connection between mental experiences and actions, shedding light on why certain situations and individuals elicit more empathy than others.

Key Facts:

Source: McGill University

In a world grappling with deep-seated division and social upheaval, empathy has become more critical than ever.

But science suggests when it comes to evoking empathy, our imagination is more powerful than we previously thought. A new study, led by McGill researchers, reveals how the different ways to experience empathy affect our willingness to help others.

Empathy is the ability to understand the situation of another person and is vital for prosocial behaviours. However, we know that empathy isnt just one thing we can experience it very differently, either as personal distress or compassionate concern for that other person, explains McGill psychology professor Signy Sheldon, and the studys co-author.

Until now, research in empathy has largely focused on how imagining helping another person can promote compassion, but not on how imagining another persons situation affects empathy, which is usually our first mental course of action.

These findings, published inthe journalEmotionbreak new ground by showing how another form of empathy, personal distress, is more prominent when imagining those situations and may actually be a catalyst for taking action to help.

The joint effort between McGill and Albany University discovered that when we vividly imagine someone elses problems in our minds, it makes us feel their pain more and motivates us to lend a helping hand.

The findings bring us closer to cracking the code of human behaviour and the link between our mental experiences and prosocial actions. These results are important for understanding why some situations and even people seem more empathetic than others.

If you hear your friend has lost a loved one or a neighbors car was stolen, what happens in your mind? Do you take on the pain of your friend or do you feel concern and compassion?

The research involved three online experiments where participants were asked to truly visualize themselves in another persons shoes.

Our experiments revealed that when people simulated distressful scenarios of other individuals, they felt much more personal distress than when these scenarios were not simulated. Interestingly, we also found imagining these scenarios in such a way increased the willingness to help that individual, says Sheldon, Canada Research Chair in Cognitive Neuroscience of Memory.

As imagining others situations is linked to episodic memory, this discovery raises significant questions about the link between memory capacity and empathy, which is an important avenue for further research.

Author: Keila DePape Source: McGill University Contact: Keila DePape McGill University Image: The image is credited to Neuroscience News

Original Research: Closed access. From memory to motivation: Probing the relationship between episodic simulation, empathy, and helping intentions by Signy Sheldon et al. Emotion

Abstract

From memory to motivation: Probing the relationship between episodic simulation, empathy, and helping intentions

Research has documented a strong link between constructingepisodic simulationsvivid imaginations of specific eventsand empathy. To date, most studies have used episodic simulations of helping someone to facilitate affective empathy and promote helping intentions, but have not studied how episodic simulations of anothers distressing situation affect empathy.

Moreover, affective empathy encompasses bothpersonal distress(i.e., an egocentric experience of distress in response to anothers circumstances) and empathic concern (i.e., compassion for another), but we do not know how episodic simulations affect each component.

To address these questions, we ran three experiments testing how different episodic simulations influenced personal distress and empathic concern, and thereby willingness to help.

In Experiment 1 (N= 216), we found that participants who constructed episodic simulations of anothers situation reported increased personal distress (but not empathic concern) and increased helping intentions compared to a control group; additional analyses revealed that personal distress mediated the simulation effect on helping.

Furthermore, in Experiment 2 (N= 213), we contrasted episodic simulation of helping versus the distressing scenario; we found no differences in personal distress or helping intentions, but simulating helping led to higher empathic concern.

Experiment 3 (N= 571) included both simulation conditions and a control condition; we fully replicated our findings, additionally showing that simulating a helping interaction increased personal distress, empathic concern, and helping intentions relative to the control condition, which consisted of prior work.

Taken together, our work illustrates how distinct forms of episodic simulation differentially guide empathic responding and highlights the importance of personal distress in motivating helping.

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Neuroscience

Peptide PACAP’s Key Role in Alcohol Addiction – Neuroscience News

Summary: Alcohol, the worlds most common addictive substance, leads to $249 billion in annual costs and 88,000 deaths in the U.S. Alcohol use disorder affects millions but is under-treated.

Researchers discovered a key player in alcohol addiction: pituitary adenylate cyclase activating polypeptide (PACAP). This peptide, found in the bed nucleus of the stria terminalis (BNST), is linked to heavy alcohol drinking and withdrawal.

Inhibiting PACAP in the BNST significantly reduces alcohol consumption, offering a potential target for novel treatments.

Key Facts:

Source: Boston University

Alcohol is the most common addictive substance in the world. Every year in the U.S. excessive alcohol use costs $249 billion and causes approximately 88,000 deaths, as well as various chronic diseases and social issues.

Alcohol use disorder, a highly prevalent, chronic, relapsing disorder, affects more than 14 million people in the U.S. alone, in addition to being severely under-treated, with only three modestly effective pharmacological therapies available.

Chronic exposure to alcohol has been shown to produce profound neuroadaptations in specific brain regions, including the recruitment of key stress neurotransmitters, ultimately causing changes in the body that sustain excessive drinking. The area of the brain known as the bed nucleus of the stria terminalis (BNST) is critically involved in the behavioral response to stress as well as in chronic, pathological alcohol use.

Researchers from Boston University Chobanian & Avedisian School of Medicine have identified that a peptide called pituitary adenylate cyclase activating polypeptide (PACAP), is involved in heavy alcohol drinking. In addition, they have discovered that this peptide acts in the BNST area.

Using an established experimental model for heavy, intermittent alcohol drinking, the researchers observed that during withdrawal this model showed increased levels of the stress neuropeptide PACAP selectively in the BNST, compared to the control model.

Interestingly, a similar increase was also observed in the levels of another stress neuropeptide closely related to PACAP, the calcitonin gene-related peptide, or CGRP. Both peptides have been implicated in stress as well as pain sensitivity, but their role in alcohol addiction is less established.

The researchers then used a virus in a transgenic model to block the neural pathways containing PACAP that specifically arrive to the BNST. We found that inhibiting PACAP to the BNST dramatically reduced heavy ethanol drinking, explained co-corresponding author Valentina Sabino, PhD, co-director of the Schools Laboratory of Addictive Disorders as well as professor of pharmacology, physiology & biophysics.

According to the researchers, these results provide evidence that this protein mediates the addictive properties of alcohol. We found a key player, PACAP, driving heavy alcohol drinking, which can be targeted for the development of novel pharmacological therapies, added co-corresponding author Pietro Cottone, PhD, associate professor of pharmacology, physiology & biophysics and co-director of the Laboratory of Addictive Disorders.

These findings appear online in the journaleNeuro.

Funding: Funding for this study was to grants number AA026051 (PC), AA025038 (VS), and AA024439 (VS) from the National Institute on Alcohol and Alcoholism (NIAAA), the Boston University Undergraduate Research Opportunities Program (UROP), the Boston University Micro and Nano Imaging Facility and the Office of the Director of the National Institutes of Health (S10OD024993).

Author: Gina DiGravio Source: Boston University Contact: Gina DiGravio Boston University Image: The image is credited to Neuroscience News

Original Research: Closed access. Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice by Valentina Sabino et al. eNeuro

Abstract

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice

Alcohol use disorder (AUD) is a complex psychiatric disease characterized by periods of heavy drinking and periods of withdrawal. Chronic exposure to ethanol causes profound neuroadaptations in the extended amygdala, which cause allostatic changes promoting excessive drinking.

The bed nucleus of the stria terminalis (BNST), a brain region involved in both excessive drinking and anxiety-like behavior, shows particularly high levels of pituitary adenylate cyclase activating polypeptide (PACAP), a key mediator of the stress response.

Recently, a role for PACAP in withdrawal-induced alcohol drinking and anxiety-like behavior in alcohol-dependent rats has been proposed; whether the PACAP system of the BNST is also recruited in other models of alcohol addiction and whether it is of local or non-local origin is currently unknown.

Here, we show that PACAP immunoreactivity is increased selectively in the BNST of C57Bl/6J mice exposed to a chronic, intermittent access to ethanol.

While PAC1R expressing cells were unchanged by chronic alcohol, the levels of a peptide closely related to PACAP, the calcitonin gene related neuropeptide (CGRP), were found to also be increased in the BNST.

Finally, using a retrograde chemogenetic approach in PACAP-ires-Cre mice, we found that the inhibition of PACAP neuronal afferents to the BNST reduced heavy ethanol drinking.

Our data suggest that the PACAP system of the BNST is recruited by chronic, voluntary alcohol drinking in mice and that non-locally originating PACAP projections to the BNST regulate heavy alcohol intake, indicating that this system may represent a promising target for novel AUD therapies.

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Peptide PACAP's Key Role in Alcohol Addiction - Neuroscience News

Neuroscience

Fruit Fly Study Sheds Light on Aggression’s Neural Roots – Neuroscience News

Summary: Researchers have discovered new insights into persistent aggression in female fruit flies, challenging existing theories.

A new study shows that certain neural cells sustain aggressive behavior for up to 10 minutes, suggesting factors beyond recurrent neural connections are at play.

These findings could aid understanding of human aggression and related neurological conditions, highlighting the need for revised models of aggression in the brain.

Key Facts:

Source: HHMI

Its one of those days. On the drive home from work, the car in the next lane cuts you off. You slam on the brakes, lay on the horn, and yell choice words at the offending driver. When you walk into your house half an hour later, youre still angry, and snap at your partner when they ask about your day.

Fruit flies may not have to worry about the lingering effects of road rage, but they also experience states of persistent aggression. In the case of female fruit flies, this behavior is a survival mechanism, causing the flies to headbutt, shove, and fence other female fruit flies to guard prime egg-laying territory on a ripe banana.

Now, researchers at Janelia and the California Institute of Technology are homing in on the neurons, circuits, and mechanisms responsible for this tenacious behavior.

In anew study, the researchers report theyve teased out the cell types contributing to a persistent aggressive state in female fruit flies, showing that some cells associated with aggression can cause flies to remain angry for up to 10 minutes.

They also found that this persistent state may not be solely due to a recurrent connection between the aggression-associated cells, as had been thought. In a recurrent connection, signals loop back and feed into the same neural circuit, which could cause a behavior to persist.

Instead, the new research suggests persistent aggression could be regulated by other factors, including neuromodulators affecting neuronal activity, neurons downstream from the aggression-associated cells, or other circuits in the fly brain. Considering their findings, scientists may need to develop a new model that considers these other factors in addition to recurrent connections to explain this enduring behavior.

It is interesting for the field because we talk about these recurrent connections as being key for the persistent state, and thats really what we thought, says Katie Schretter, a postdoc in the Rubin Lab who led the research. But now it seems less clear in this case.

Understanding persistent internal states like aggression could help researchers better uncover how the brain makes decisions for instance, whether to stay mad or move on and the individual circuits involved in these choices. Figuring out the underlying mechanisms behind aggression could also help scientists better understand aggressive behavior in humans, including behaviors that can occur alongside neurodegenerative or psychiatric diseases.

For our society, its important to be able to decrease aggression and figure out how to stop persistent aggression, Schretter says. Figuring out how the circuit works can help us figure out how we might decrease it.

Fighting fruit flies

Scientists had previously identified cell types associated with aggression in the brains of female fruit flies. They found that activating these cells caused the flies to fight. Given this, the team, led by Schretter, Cal Tech graduate student Hui (Vivian) Chiu, Janelia Senior Group Leader Gerry Rubin, and HHMI Investigator David Anderson, wanted to look at these cells to see how their signals might feed back into each other to generate a persistent aggressive state.

The researchers separated female flies with a barrier and then activated the different cell types associated with aggression for 30 seconds at a time. They kept the flies separated for specific periods of time, up to 30 minutes, before removing the barrier and letting them interact.

The team hypothesized that recurrent connections between certain aggression-associated cell types could cause the flies to remain aggressive for longer periods of time.

They found that one cell type associated with aggression aIPg contributes to persistent aggression. When these cells were activated, the flies would fight for up to 10 minutes after the barrier was removed. But another cell type previously found to be involved in aggression pC1d did not cause this same enduring anger.

pC1d also didnt affect whether aIPg caused persistent aggression, and neither pC1d nor aIPg showed persistent neuronal activity. These findings suggest that a persistent aggressive state doesnt depend on a recurrent connection between the two cell types.

Previous research had shown that stimulating another cell associated with aggression pC1e also does not cause persistent behavior on its own. However, Schretter and colleagues were surprised to find that when pC1d and pC1e were stimulated simultaneously, the flies remained persistently aggressive.

Taken together, the results suggest that the persistent aggressive state may be maintained by a mechanism different from what the researchers had originally thought. Instead of being due to a recurrent connection between aIPg and pC1d, as they had hypothesized, persistent aggression could involve pC1e.

But it could also include other factors, such as a neuromodulator acting on the circuit or the effect of neurons downstream from aIPg, pC1d, and pC1e. Or aggression could be controlled by another circuit altogether.

Schretter says investigating these other models to explain persistent aggression is the next step.

Its exciting to see what else could lengthen that persistence, because there could be other circuits that are also involved, she says. It is basically open for us to go after, so it is a fun place to be.

Author: Nanci Bompey Source: HHMI Contact: Nanci Bompey HHMI Image: The image is credited to the CDC and is in the public domain

Original Research: Open access. Cell type-specific contributions to a persistent aggressive internal state in femaleDrosophila by Katie Schretter et al. eLife

Abstract

Cell type-specific contributions to a persistent aggressive internal state in femaleDrosophila

Persistent internal states are important for maintaining survival-promoting behaviors, such as aggression. In femaleDrosophila melanogaster, we have previously shown that individually activating either aIPg or pC1d cell types can induce aggression.

Here we investigate further the individual roles of these cholinergic, sexually dimorphic cell types, and the reciprocal connections between them, in generating a persistent aggressive internal state.

We find that a brief 30-second optogenetic stimulation of aIPg neurons was sufficient to promote an aggressive internal state lasting at least 10 minutes, whereas similar stimulation of pC1d neurons did not.

While we previously showed that stimulation of pC1e alone does not evoke aggression, persistent behavior could be promoted through simultaneous stimulation of pC1d and pC1e, suggesting an unexpected synergy of these cell types in establishing a persistent aggressive state.

Neither aIPg nor pC1d show persistent neuronal activity themselves, implying that the persistent internal state is maintained by other mechanisms.

Moreover, inactivation of pC1d did not significantly reduce aIPg-evoked persistent aggression arguing that the aggressive state did not depend on pC1d-aIPg recurrent connectivity.

Our results suggest the need for alternative models to explain persistent female aggression.

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Fruit Fly Study Sheds Light on Aggression's Neural Roots - Neuroscience News