Category Archives: Neuroscience

Neuroscience

When Unconscious, the Brain Is Anything but ‘Silent’ – Neuroscience News

Summary: Some neurons in the cerebral cortex show higher spontaneous activity during general anesthesia than when awake, and this activity is synchronized across the cortical cells.

Source: University of Basel

The cerebral cortex is thought to be the seat of conscious processing in the brain. Rather than being inactivated, specific cells in the cortex show higher spontaneous activity during general anesthesia than when awake, and this activity is synchronized across those cortical cells.

Improving our understanding of the neuronal mechanisms of general anesthesia could lead to better anesthetic drugs and improved surgical outcomes.

In a paper recently published inNeuron, researchers from the group of Professor Botond Roska at the University of Basel and the Institute of Molecular and Clinical Ophthalmology (IOB) reveal how different cell types incortexchange their activity duringgeneral anesthesia, helping to understand how unconsciousness may be induced.

You are lying on the operating table. The doctor tells you to count to 5, and places ananestheticmask on your face. By the count of 4, youve lost consciousness. You will not wake up until after the surgery. What happened in yourbrainduring this time?

One would probably assume that your brain has been silent. Especially your cortex, the brain area thought to be the seat of conscious processing. However, for close to 100 years, it has been known that some cells in the cortex are active and that cortex alternates between periods of high and low activity during general anesthesia.

Using EEG electrodes attached to the scalp is one of the few tools available to measure this activity, but electrodes dont allow one to identify the cells underlying this activity. Therefore, the question has remained: which cells contribute to the rhythmic activity in the cortex, and how might that contribute to the loss of consciousness during general anesthesia.

On the trail of unconsciousness

Cortex is composed of different cell types, each with different functions. Different general anesthetics act on different receptors, located on different types of neurons, distributed throughout the brain.

Yet, all general anesthetics lead to the loss of consciousness, so we were interested in finding if there is a common neuronal mechanism across different anesthetics, says Dr. Martin Munz, one of the three first authors of the study.

In thisNeuronpublication, the researchers used modern genetic tools, in combination with mouse lines labeling individual cortical cell types to address this question. They found that in contrast to what had previously been suspected, only one specific cell type within cortex, layer 5pyramidal neurons, showed an increase in activity when the animal was exposed to different anesthetics.

Each anesthetic induces a rhythm of activity in layer 5 pyramidal neurons. Interestingly, these rhythms differed between anesthetics. Some were slower, and some were faster. However, what was common across all anesthetics was that they all induced an alignment of activity. That is, when they were active, all layer 5 pyramidal neurons were active at the same time, says Dr. Arjun Bharioke from the same research group and also a first author of the study.

We called this neuronal synchrony'.

Layer 5 pyramidal neurons serve as a major output center for thecerebral cortexand also connect different cortical areas to each other. Thus, they communicate both between different cortical areas, as well as from the cortex to other areas of the brain. Therefore, a synchronization of activity across layer 5 pyramidal neurons restricts the information that the cortex can output.

Like a crowd at a soccer match

It seems that instead of each neuron sending different pieces of information, during anesthesia all layer 5 pyramidal neurons send the same piece of information, says Arjun Bharioke,

One could think of this as when people in a crowd transition from talking to each other, for example before a soccer or basketball game, to when they are cheering for their team, during the game. Before the game starts, there are many independent conversations. In contrast, during the game, all the spectators are cheering on their team. Thus, there is only one piece of information being transmitted across the crowd.

Prior work has proposed thatloss of consciousnessoccurs through the disconnection of cortex from the rest of the brain. The results of the IOB team suggest a mechanism by which this may occurby the transition to lowered information output from cortex, during anesthesia.

Alexandra Brignall, the third first author and a veterinarian by trade says: Anesthetics are very powerful, as anyone who has been in a surgery can attest to. But they are also not always easy to use.

During a surgery, one has to continuously monitor the depth of the anesthetic to ensure that the patient is not too deep or too shallow. The more we know how anesthetics work and what they do in the brain, the better. Maybe this will help researchers develop new drugs to more specifically target thecellsin the brain associated with unconsciousness.

Our findings are highly relevant for medicine, since anesthesia is one of the most frequently performed medical procedures. Understanding the neuronal mechanism ofanesthesiacould lead to betteranesthetic drugsand improved surgical outcomes, says Botond Roska, corresponding author and director of the IOB Molecular Research Center.

Author: Press OfficeSource: University of BaselContact: Press Office University of BaselImage: The image is in the public domain

Original Research: Open access.General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons by Arjun Bharioke et al. Neuron

Abstract

General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons

General anesthetics induce loss of consciousness, a global change in behavior. However, a corresponding global change in activity in the context of defined cortical cell types has not been identified.

Here, we show that spontaneous activity of mouse layer 5 pyramidal neurons, but of no other cortical cell type, becomes consistently synchronizedinvivoby different general anesthetics. This heightened neuronal synchrony is aperiodic, present across large distances, and absent in cortical neurons presynaptic to layer 5 pyramidal neurons.

During the transition to and from anesthesia, changes in synchrony in layer 5 coincide with the loss and recovery of consciousness. Activity within both apical and basal dendrites is synchronous, but only basal dendrites activity is temporally locked to somatic activity.

Given that layer 5 is a major cortical output, our results suggest that brain-wide synchrony in layer 5 pyramidal neurons may contribute to the loss of consciousness during general anesthesia.

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When Unconscious, the Brain Is Anything but 'Silent' - Neuroscience News

Neuroscience

What Makes Some More Afraid of Change Than Others? – Neuroscience News

Summary: Differences in gene expression in key brain areas may account for the reason some are less fearful of change than others.

Source: LSU

Humans are undoubtedly altering the natural environment. But how wild animals respond to these changes is complex and unclear.

In anew study, scientists have discovered significant differences in how the brain works in two distinct personality types: those who act fearless and those who seem afraid of new things.

Being fearless can help wildlife, specifically birds, find new food sources, explore new nesting areas and help them adapt to changes in their environment; but being afraid can also help protect them from dangerous novel things in their environment such as cars.

Our study provides interesting and important evidence that some of the behavior differences could be led by gene expression, said LSU Department of Biological Sciences Assistant Professor Christine Lattin, who is the lead author on thepaperpublished byPLOS ONEtoday.

Social creatures, such as house sparrows,can learn from each other, so having a mixture of both personality types in a flock could be part of the reason this species is so successful in human-altered environments.

Scientists have found that within the flock, the genes expressed, or turned on, in the brains of the fearless birds are markedly different from those in the birds that exhibit fear. In fact, three out of the four regions of the brain studied showed differences.

The hippocampus, which is associated with learning, memory and spatial navigation, contrasted the most amongst the two personality types.

One of the interesting things about the hippocampus is it can play an important role in decision-making. For example, when wildlife are presented with something new in their environment, the genes in their brains respond, helping them process the information, compare it to past experience and decide whether they should approach or avoid the novel object, Lattin said.

The scientists compared six wild, invasive female house sparrows: three of which acted fearless and three that seemed afraid to approach a new object at their feeding dish.

The novel objects were a red wrist coil keychain wrapped around the food dish, a white plastic cover over part of the food dish, a green plastic Easter egg placed on top of the food in the middle of the dish, a normal silver food dish painted red on the outside and a blinking light hung above and directed towards the front of the dish.

The fearless birds fed at the food dish regardless of the presence of the novel objects while the fearful birds avoided the food dish in the presence of the novel objects.

Several weeks after behavior testing, the scientists examined gene expression in four brain regions in these sparrows. The genes that were expressed in the hippocampus of the fearless birds were different from the genes expressed in the hippocampus of the fearful birds.

For example, there were many more dopamine receptor 2 transcripts present in the fearless birds. Dopamine receptor 2 has been associated with boldness and exploration. In contrast, the birds that avoided the new objects had more transcripts for the estrogen receptor beta gene, which has been associated with anxiety.

The fear of new things, or neophobia, is a problem some people struggle with. The neurobiological gene receptors weve identified could help other scientists develop drugs to target neophobia or anxiety even in our own species, Lattin said.

Advances in sequencing technology have made it possible to study neurological gene expression in more wild species.

It used to be very expensive, but technology has made it faster and cheaper to do these types of analyses. Now that it has become more accessible, more scientists are doing this type of research, Lattin said.

Author: Press OfficeSource: LSUContact: Press Office LSUImage: The image is in the public domain

Original Research: Open access.Constitutive gene expression differs in three brain regions important for cognition in neophobic and non-neophobic house sparrows by Christine Lattin et al. PLOS ONE

Abstract

Constitutive gene expression differs in three brain regions important for cognition in neophobic and non-neophobic house sparrows

Neophobia (aversion to new objects, food, and environments) is a personality trait that affects the ability of wildlife to adapt to new challenges and opportunities. Despite the ubiquity and importance of this trait, the molecular mechanisms underlying repeatable individual differences in neophobia in wild animals are poorly understood.

We evaluated wild-caught house sparrows (Passer domesticus) for neophobia in the lab using novel object tests. We then selected a subset of neophobic and non-neophobic individuals (n = 3 of each, all females) and extracted RNA from four brain regions involved in learning, memory, threat perception, and executive function: striatum, caudal dorsomedial hippocampus, medial ventral arcopallium, and caudolateral nidopallium (NCL).

Our analysis of differentially expressed genes (DEGs) used 11,889 gene regions annotated in the house sparrow reference genome for which we had an average of 25.7 million mapped reads/sample. PERMANOVA identified significant effects of brain region, phenotype (neophobic vs. non-neophobic), and a brain region by phenotype interaction.

Comparing neophobic and non-neophobic birds revealed constitutive differences in DEGs in three of the four brain regions examined: hippocampus (12% of the transcriptome significantly differentially expressed), striatum (4%) and NCL (3%).

DEGs included important known neuroendocrine mediators of learning, memory, executive function, and anxiety behavior, including serotonin receptor 5A, dopamine receptors 1, 2 and 5 (downregulated in neophobic birds), and estrogen receptor beta (upregulated in neophobic birds).

These results suggest that some of the behavioral differences between phenotypes may be due to underlying gene expression differences in the brain.

The large number of DEGs in neophobic and non-neophobic birds also implies that there are major differences in neural function between the two phenotypes that could affect a wide variety of behavioral traits beyond neophobia.

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What Makes Some More Afraid of Change Than Others? - Neuroscience News

Neuroscience

Excessive Sports Training May Have Negative Effects on Mood State – Neuroscience News

Summary: Intense sports training may be good for the body, but it might not always be so good for the mind. Researchers found the more intense a training session is, the lower both mood and heart rate variability are the next day.

Source: UAB

To build fitness, athletes must apply stress to the body, and then through recovery, the body adapts and is able to accommodate greater stress in the next round of training. Controlling the adequate amounts of stress and recovery is essential to ameliorate the performance of athletes, as well as to prevent injuries and problems associated with overtraining.

Researchers from the Laboratory of Sport Psychology and the Sport Research Institute at the UAB have studied the effectstrainingintensity has on road cyclists in terms of mood states and their capacity to adapt to greater training loads, assessed usingheart rate variability(HRV).

The research, published in the journalPeerJ, was conducted through a six-week analysis of the answers five amateur road cyclists gave of the physical stress they endured during training. Once completed, the cyclists also responded to questionnaires on how they had perceived the physical exertion of their training. The following morning they measured their HRV and recorded theirmood state.

The researchers argue that a change in mood and/or HRVmeasured using the HFnu (normalized high frequency band) parameterinathletesthe day after training could serve as indicator of training intensity, signaling whether the training had been adequate or too intense for the physical state of the athlete.

The study observed that the more intense the training, the lower the mood on the following day, and also the lower the HRV. In contrast, high HFnu was associated with an improvement in the mood of athletes, which indicated that there is a relationship between HRV and mood states.

The objective of the research was to explore the relation among three aspects: training, heart rate variability and mood, explains researcher of the UAB Department of Basic Psychology Carla Alfonso.

With this study we aimed to know when an athlete must rest, because their system is saturated, and when an athlete can train, with more or less intensity, because their body is ready to assimilate the training load.

The results obtained are a first step in setting up a monitoring system which takes into account both internal and external training loads, in addition to mood state and heart rate variability of the athlete, with the aim of helping them adapt to their training and prevent injuries that may come with overtraining, concludes Professor Llus Capdevila of the UAB Department of Basic, Developmental and Educational Psychology, and co-author of the study.

Author: Press OfficeSource: UABContact: Press Office UABImage: The image is in the public domain

Original Research: Open access.Heart rate variability, mood and performance: a pilot study on the interrelation of these variables in amateur road cyclists by Carla Alfonso et al. PeerJ

Abstract

Heart rate variability, mood and performance: a pilot study on the interrelation of these variables in amateur road cyclists

The present study seeks to explore the relationship between measures of cycling training on a given day and the heart rate variability (HRV) and mood states obtained the following morning. The association between HRV and mood state is also studied, as is the relationship between internal and external measures of training.

During a 6-week period, five recreational road cyclists collected 123 recordings of morning HRV and morning mood, and 66 recordings of training power and rate of perceived exertion (RPE). Training power was used as an external measure of performance and RPE as an internal measure of performance. The HRV parameters used in the study were the mean of RR intervals (mean RR) and the standard deviation of all RR intervals (SDNN) as time domain analysis, and the normalized high frequency band (HFnu), normalized low frequency band (LFnu) and the ratio between low and high frequency bands, as frequency domain analysis. Mood was measured using a 10-point cognitive scale.

It was found that the higher the training power on a given day, the lower the HFnu and the higher LF/HF were on the following morning. At the same time, results showed an inverse relationship between training and mood, so the tougher a training session, the lower the mood the following day. A relationship between morning HRV and mood was also found, so that the higher mean RR and HFnu, the more positive the mood (r = 0.497 and r = 0.420 respectively;p< 0.001). Finally, RPE correlated positively with external power load variables (IF: r = 0.545;p< 0.001).

Altogether, the results indicate a relationship between training of cyclists on a given day and their morning HRV and mood state on the following day. Mood and HRV also seem positively related. It is argued that developing a monitoring system that considers external and internal training loads, together with morning mood, could help understand the state of the individual, enabling feedback to athletes to facilitate the adaptation to training and to prevent problems associated with overtraining. However, more research is needed to further understand the association between the different variables considered.

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Excessive Sports Training May Have Negative Effects on Mood State - Neuroscience News

Neuroscience

New Study Reveals How the Brain Says Oops! – Neuroscience News

Summary: Researchers identified a group of neurons in the frontal lobe that enables flexibility to learn new skills and the focus to develop sophisticated skills. The brain uses the same group of neurons for performance feedback in a variety of situations.

Source; Cedars Sinai

Researchers from Cedars-Sinais Center for Neural Science and Medicine and Department of Neurosurgery have uncovered how signals from a group of neurons in the brains frontal lobe simultaneously give humans the flexibility to learn new tasksand the focus to develop highly specific skills.

Their research, published today in the peer-reviewed journalScience,provides a fundamental understanding of performance monitoring, an executive function used to manage daily life.

The studys key finding is that the brain uses the same group of neurons for performance feedback in many different situationswhether a person is attempting a newtaskfor the first time or working to perfect a specific skill.

Part of the magic of the human brain is that it is so flexible, said Ueli Rutishauser, Ph.D., professor of Neurosurgery, Neurology, and Biomedical Sciences, director of the Center for Neural Science and Medicine, the Board of Governors Chair in Neurosciences and senior author of the study. We designed our study to decipher how the brain can generalizeandspecialize at the same time, both of which are critical for helping us pursue a goal.

Performancemonitoringis an internal signal, a kind of self-generated feedback, that lets a person know they have made a mistake. One example is the person who realizes they drove past an intersection where they should have turned. Another example is the person who says something in conversation and recognizes as soon as the words are out of their mouth that what they just said was inappropriate.

That Oh, shoot moment, that Oops! moment, is performance monitoring kicking in, said Zhongzheng Fu, Ph.D., a postdoctoral researcher in the Rutishauser Laboratory at Cedars-Sinai and first author of the study.

These signals help improve performance on future attempts by passing information to areas of the brain that regulate emotions, memory, planning and problem-solving. Performance monitoring also helps the brain adjust its focus by signaling how much conflict or difficulty was encountered during the task.

So an Oops! moment might prompt someone to pay closer attention the next time they chat with a friend or plan to stop at the store on the way home from work, said Fu.

To see performance monitoring in action, investigators recorded the activity of individual neurons in the medial frontal cortex of study participants. The participants wereepilepsy patientswho, as part of their treatment, had electrodes implanted in their brains to help locate the focus of their seizures. Specifically, these patients had electrodes implanted in the medial frontal cortex, a brain region known to play a central role in performance monitoring.

In the Stroop task, which pits reading against color naming, participants viewed the written name of a color, such as red, printed in ink of a different color, such as green, and were asked to name the ink color rather than the written word.

This creates conflict in the brain, Rutishauser said. You have decades of training in reading, but now your goal is to suppress that habit of reading and say the color of the ink that the word is written in instead.

In the other task, the Multi-Source Interference Task (MSIT), which involves recognizing numerals, participants saw three numerical digits on screen, two the same and the other uniquefor example, 1-2-2. The subjects task was to press the button associated with the unique numberin this case, 1resisting their tendency to press 2 because that number appears twice.

These two tasks serve as a strong test of how self-monitoring is engaged in different scenarios involving different cognitive domains, Fu said.

A structured response

As the subjects performed these tasks, the investigators noted two different types of neurons at work. Error neurons fired strongly after an error was made, while conflict neurons fired in response to the difficulty of the task the subject had just performed.

When we observed the activity of neurons in this brain area, it surprised us that most of them only become active after a decision or an action was completed. This indicates that this brain area plays a role in evaluating decisions after the fact, rather than making them.

There are two types of performance monitoring: domain general and domain specific. Domain general performance monitoring tells ussomethingwent wrong and can detect errors in any type of taskwhether someone is driving a car, navigating a social situation or playing Wordle for the first time. This allows them to perform new tasks with little instruction, something machines cannot do.

Machines can be trained to do one thing really well, Fu said. You can build a robot to flip hamburgers, but it cant adapt those skills to frying dumplings. Humans, thanks to domain general performance monitoring, can.

Domain specific performance monitoring tells the person who made the errorwhatwent wrong, detecting specific mistakesthat they missed a turn, said something inappropriate or chose the wrong letter in a puzzle. This is one way people perfect individual skills.

Surprisingly, neurons signaling domain general and domain specific information were intermingled in the medial frontal cortex.

We used to think there were portions of the brain dedicated to only domain general performance monitoring and others to only domain specific, Rutishauser said.

Our study now shows thats not the case. Weve learned that the very same group of neurons can do both domain general and domain specific performance monitoring. When youre listening to these neurons, you can read out both types of information simultaneously.

To understand how these signals are interpreted by other areas of the brain, it helps to think of the neurons as musicians in an orchestra, Rutishauser said.

If they all play at random, the listenersin this case the regions of thebrainreceiving the signalsjust hear a garbled set of notes, Rutishauser said.

But if they play an arranged composition, its possible to clearly hear the various melodies and harmonies even with so many instrumentsor performance monitoring neuronsplaying all at once.

Too much or too little of this signaling, however, can cause problems, Rutishauser said.

Overactive performance monitoring can manifest asobsessive-compulsive disorder, causing a person to check obsessively for errors that dont exist. At the other extreme is schizophrenia, where performance monitoring can be underactive to a degree that a person doesnt perceive errors or the inappropriateness of their words or actions.

We believe the mechanistic knowledge we have gained will be critical to perfecting treatments for these devastating psychiatric disorders, Rutishauser said.

The research team also included Jeffrey Chung, MD, director of the Cedars-Sinai Epilepsy Program; Assistant Professor of Neurology Chrystal Reed, MD, Ph.D.; Adam Mamelak, MD, professor of neurosurgery and director of the Functional Neurosurgery Program; Ralph Adolphs, Ph.D., professor of Psychology, Neuroscience, and Biology at the California Institute of Technology; and research associate Danielle Beam.

Author: Press OfficeSource: Cedars SinaiContact: Press Office Cedars SinaiImage: The image is in the public domain

Original Research: Closed access.The geometry of domain-general performance monitoring in the human medial frontal cortex by Zhongzheng Fu et al. Science

Abstract

The geometry of domain-general performance monitoring in the human medial frontal cortex

Controlling behavior to flexibly achieve desired goals depends on the ability to monitor ones own performance. It is unknown how performance monitoring can be both flexible, to support different tasks, and specialized, to perform each task well.

We recorded single neurons in the human medial frontal cortex while subjects performed two tasks that involve three types of cognitive conflict. Neurons encoding conflict probability, conflict, and error in one or both tasks were intermixed, forming a representational geometry that simultaneously allowed task specialization and generalization. Neurons encoding conflict retrospectively served to update internal estimates of conflict probability. Population representations of conflict were compositional.

These findings reveal how representations of evaluative signals can be both abstract and task-specific and suggest a neuronal mechanism for estimating control demand.

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New Study Reveals How the Brain Says Oops! - Neuroscience News

Neuroscience

Links Between Paranormal Beliefs and Cognitive Function Described by 40 Years of Research – Neuroscience News

Summary: A review of 71 studies over 40 years aligns with the hypothesis that belief in the paranormal is associated with differences and deficits in cognitive function.

Source: PLOS

In a review of 71 studies that explored links between belief in paranormal phenomena and cognitive function, most of the findings align with the hypothesis that such beliefs are associated with cognitive differences or deficits.

Charlotte E. Dean and colleagues at the University of Hertfordshire, U.K., present this evaluation in the open-access journalPLOS ONE.

For several decades, researchers have examined potential links betweencognitive functioningand belief in paranormal phenomena, such as psychokinesis, hauntings, and clairvoyance. However, about 30 years have passed since a non-systematic review of this literature was last conducted.

To provide updated insights into the findings and quality of studies on this topic, Dean and colleagues systematically identified and evaluated 70 published studies and one unpublished doctoral thesis produced between 1980 and 2020.

The 71 studies explored a range of cognitive functions, such as reasoning ability, thinking style, and memory.

Overall, the findings align with the hypothesis that beliefs in paranormal phenomena are associated with differences or deficits in cognitive function. For example, a particularly consistent association was found between paranormal beliefs and an intuitive thinking style.

The review found that most of the 71 studies were of good methodological quality and that quality has improved over time; for instance, most had clear objectives and appropriate study designs.

However, certain areas for improvement emerged; for instance, many studies lacked a discussion of their own methodological limitations, andundergraduate studentsmade up a large portion of study participants, meaning that the findings may not necessarily apply to thegeneral population.

The authors note that no specific profile of cognitive functioning for paranormal believers has emerged from this literature. They suggest that future research could not only address the methodological weaknesses they observed, but also explore the possibility that paranormal beliefs might be associated with a more overarching difference of cognitionwhich could help explain why past studies have found links with seemingly disparate types of cognitive dysfunction.

The authors add: Four decades of research suggests that belief in the paranormal is linked to our degree of cognitive flexibility and fluid intelligence; however, methodological improvements in future research are required to further our understanding of the relationship.

Author: Press OfficeSource: PLOSContact: Press Office PLOSImage: The image is in the public domain

Original Research: Open access.Paranormal beliefs and cognitive function: A systematic review and assessment of study quality across four decades of research by Charlotte E. Dean et al. PLOS ONE

Abstract

Paranormal beliefs and cognitive function: A systematic review and assessment of study quality across four decades of research

Research into paranormal beliefs and cognitive functioning has expanded considerably since the last review almost 30 years ago, prompting the need for a comprehensive review. The current systematic review aims to identify the reported associations between paranormal beliefs and cognitive functioning, and to assess study quality.

We searched four databases (Scopus, ScienceDirect, SpringerLink, and OpenGrey) from inception until May 2021. Inclusion criteria comprised papers published in English that contained original data assessing paranormal beliefs and cognitive function in healthy adult samples. Study quality and risk of bias was assessed using the Appraisal tool for Cross-Sectional Studies (AXIS) and results were synthesised through narrative review.

The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was preregistered as part of a larger registration on the Open Science Framework (https://osf.io/uzm5v).

From 475 identified studies, 71 (n = 20,993) met our inclusion criteria. Studies were subsequently divided into the following six categories: perceptual and cognitive biases (k = 19, n = 3,397), reasoning (k = 17, n = 9,661), intelligence, critical thinking, and academic ability (k = 12, n = 2,657), thinking style (k = 13, n = 4,100), executive function and memory (k = 6, n = 810), and other cognitive functions (k = 4, n = 368).

Study quality was rated as good-to-strong for 75% of studies and appears to be improving across time. Nonetheless, we identified areas of methodological weakness including: the lack of preregistration, discussion of limitations, a-priori justification of sample size, assessment of nonrespondents, and the failure to adjust for multiple testing.

Over 60% of studies have recruited undergraduates and 30% exclusively psychology undergraduates, which raises doubt about external validity. Our narrative synthesis indicates high heterogeneity of study findings.

The most consistent associations emerge for paranormal beliefs with increased intuitive thinking and confirmatory bias, and reduced conditional reasoning ability and perception of randomness.

Although study quality is good, areas of methodological weakness exist. In addressing these methodological issues, we propose that authors engage with preregistration of data collection and analysis procedures. At a conceptual level, we argue poorer cognitive performance across seemingly disparate cognitive domains might reflect the influence of an over-arching executive dysfunction.

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Links Between Paranormal Beliefs and Cognitive Function Described by 40 Years of Research - Neuroscience News

Neuroscience

Does Autism Begin in the Womb? – Neuroscience News

Summary: Researchers found idiopathic autism occurs as the result of epigenetic abnormalities in hematopoietic cells during fetal development, leading to immune dysregulation in the brain and gut.

Source: Kobe University

Autism (autism spectrum disorder) is a developmental neurological disorder that remains largely unexplored despite the rapidly increasing number of patients. Immune abnormalities, now considered the cause of many diseases, also play an important role in the development of autism.

Brain inflammation and disturbances of the peripheral immune system are frequently observed in autistic patients. Furthermore, immune abnormalities are accompanied by abnormalities in the intestinal microbiota, which is also thought to be involved in the pathogenesis of the disease via the brain-gut axis.

However, the essential mechanisms behind these immune abnormalities have yet to be elucidated.

Given the critical developmental stages of immune insults and the extensive involvement of the immune system in the development of autism, the research team hypothesized that a common etiology underlies the widespread immune dysregulation and originates in different types of progenitor cells.

The analysis focused on the hematopoietic cells from which immune cells are derived, as well as on the yolk sac (YS) and the aorta-gonad-mesonephros (AGM), which are involved in hematopoiesis during the fetal stage.

These results seek a common ancestor of inflammation in the brain and abnormalities in the peripheral immune system. In this study, BTBR mice were used as an idiopathic model for autism.

Research Findings

Single-cell RNA sequencing (sc-RNA seq) of BTBR mice traced the origin of immune abnormalities back to the embryonic stages of the yolk sac (YS) and aorta-gonad-mesonephros (AGM) and identified where macrophages (microglia) and peripheral immune cells differentiate.

Definitive hematopoiesisin YS and AGM single-cell level analysis successfully identified pathological mechanisms at the molecular level within rare progenitor cells in the early stages of development. Namely, we found a common mechanism of transcriptional regulation through HDAC1, a histone deacetylase, underlying these pathologies.

We have also shown that manipulating epigenetic mechanisms during specific developmental stages can restore immune abnormalities in the brain and peripheral tissues. Namely, we identified histone deacetylase HDAC1 as a common mechanism.

Administrating inhibitors of this histone (sodium butyrate or Romidepsin) during the fetal stage in BTBR mice suppressed elevated inflammatory cytokinesand microglial activation.

We further demonstrated that dysregulated immunity can determine gut dysbiosis of specific profiles in autistic model mice, which make the potential biomarkers of Treg and gut dysbiosis a means to categorize the immune-dysregulated ASD subtype.

From the above, it is clear that the abnormalities in the brain and peripheral organs (such as the intestines) seen in autism are caused by epigenetic abnormalities in the hematopoietic stem cell lineage, the ancestor of immune cells.

Perspectives

Our findings not only provide the missing piece to solve the long-time puzzle of systemic immune dysregulation in autism, but also hint the role of epigenetic disturbance as common etiology among different autism models of environmental risk factors.

Furthermore, to develop precision medicine for ASD in the future, ASD subtyping according to the pathogenesis mechanism is a key first step to resolve the heterogeneity of ASD and to open up a new avenue for ASD treatment.

Author: Verity TownsendSource: Kobe UniversityContact: Verity Townsend Kobe UniversityImage: The image is in the public domain

Original Research: Open access.A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model by Toru Takumi et al. Molecular Psychiatry

Abstract

A common epigenetic mechanism across different cellular origins underlies systemic immune dysregulation in an idiopathic autism mouse model

Immune dysregulation plays a key role in the pathogenesis of autism. Changes occurring at the systemic level, from brain inflammation to disturbed innate/adaptive immune in the periphery, are frequently observed in patients with autism; however, the intrinsic mechanisms behind them remain elusive.

We hypothesize a common etiology may lie in progenitors of different types underlying widespread immune dysregulation. By single-cell RNA sequencing (sc-RNA seq), we trace the developmental origins of immune dysregulation in a mouse model of idiopathic autism.

It is found that both in aorta-gonad-mesonephros (AGM) and yolk sac (YS) progenitors, the dysregulation of HDAC1-mediated epigenetic machinery alters definitive hematopoiesis during embryogenesis and downregulates the expression of the AP-1 complex for microglia development.

Subsequently, these changes result in the dysregulation of the immune system, leading to gut dysbiosis and hyperactive microglia in the brain.

We further confirm that dysregulated immune profiles are associated with specific microbiota composition, which may serve as a biomarker to identify autism of immune-dysregulated subtypes.

Our findings elucidate a shared mechanism for the origin of immune dysregulation from the brain to the gut in autism and provide new insight to dissecting the heterogeneity of autism, as well as the therapeutic potential of targeting immune-dysregulated autism subtypes.

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Does Autism Begin in the Womb? - Neuroscience News

Neuroscience

Dopamine Involved in Recognizing Emotions – Neuroscience News

Summary: Researchers reveal dopamine, a neurotransmitter commonly associated with reward plays a key role in social cognition and emotional recognition.

Source: SfN

The neurotransmitter dopamine, famous for its role in reward, is also involved in recognizing emotions, according to new research published inJournal of Neuroscience.

People with disrupted dopamine levels, likein Parkinsons disease and schizophrenia, often struggle with aspects of social cognition.

Yet the link between dopamine and specific social behaviors remained elusive, in part due to mixed results from studies that did not account for individual differences in dopamine levels.

In a study by Schuster et al., healthy participants took haloperidol a dopamine receptor inhibitor on one day and a placebo pill on another before completing an emotion recognition task.

They assessed videos of people expressing an emotion through their posture and gait (i.e., slow movements for sadness, quick, jerky movements for anger). The researchers also indirectly measured each persons baseline dopamine levels by testing their working memory.

The effects of haloperidol varied in each person depending on their baseline dopamine levels. In people with low dopamine, the drug increased their ability to recognize emotions, while in people with high dopamine, the drug impaired their ability.

Future work will examine how changes in dopamine levels in disorders like Parkinsons disease contribute to social cognition impairments.

Author: Calli McMurraySource: SfNContact: Calli McMurray SfNImage: The image is in the public domain

Original Research: Closed access.Dopaminergic modulation of dynamic emotion perception by B.A. Schuster,S. Sowden,A.J. Rybicki,D.S. Fraser,C. Press,P. HollandandJ.L. Cook. Journal of Neuroscience

Abstract

Dopaminergic modulation of dynamic emotion perception

Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinsons disease).

Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioural modulation.

Interestingly, whilst a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences.

The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo.

To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing.

Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition.

Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing.

Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition.

Significance statement

A high prevalence of emotion recognition difficulties amongst clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes.

However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights.

The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition.

Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.

Link:
Dopamine Involved in Recognizing Emotions - Neuroscience News

Neuroscience

WVU Today | WVU experiential business learning, health care outreach and personalized nursing bolstered by couple’s $1.8M gift – WVU Today

Rusty and Kimberly Hutson (at center) pose with children (from left) Conner, Parker, Tanner and Hannah. (Submitted Photo)

A $1.8 million gift to West Virginia University from Mountain State natives Kimberly and Rusty Hutson, Jr., will bolster education, health care and outreach efforts to aid residents across the state.

The Hutsons contribution provides $1 million to support namesake fellowships in experiential learning and applied service at the John Chambers College of Business and Economics, $400,000 to aid the West Virginia Faith Community Nursing Initiative at the School of Nursing, and $400,000 to expand personalized care for neuroscience patients and their families at the Rockefeller Neuroscience Institute.

Kimberly and I are thrilled to give to these three quality programs at WVU, Rusty Hutson said.We have been blessed as a family, and we are passionate about giving back to our home state that we love so much. These gifts are strategic for us as a family, as we look to assist in enhancing quality health care for rural areas of the state as well as provide support for the world-class Rockefeller Neuroscience Institute.In addition, the Hutson Fellows program will not only assist students in furthering their business education in a real business setting but will encourage them to remain in West Virginia as they begin their business careers. We are honored to provide the financial support needed to develop and enhanceall three programs.

The Rusty & Kimberly Hutson Fellowships in Experiential Learning will expand employment opportunities available to Chambers College students in recognition of their academic performance and professional promise. Honorees will participate in paid student work that simultaneously allows them to gain real-world experience, connect with industry, and serve the state and people of West Virginia.

This generous investment from Rusty and Kimberly Hutson will allow us to greatly expand experiential learning opportunities to our business students, which is at the core of our purpose in the Chambers College as we move into Reynolds Hall in a few short months, said Josh Hall, Milan Puskar Dean. They will be market-ready and prepared to solve the business problems of the future because of the hands-on learning experiences this gift will provide, while also honoring our land-grant mission as a university and learning the importance of service to our state.

The Hutsons gift to support the West Virginia Faith Community Nursing Initiative will allow the School of Nursing to partner with nurses throughout the state to provide health screenings, education and more at community faith centers. The goal is to expand access to health care, particularly in the states most rural and economically challenged counties.

Meeting people where they are is an essential component of health care, said Tara Hulsey,dean of the School of Nursing and E. Jane Martin Endowed Professor. This generous gift from the Hutsons will help provide greater access to care in the areas that need it most.

The couples contribution to the Rockefeller Neuroscience Institute will enhance personalized patient care at the RNI. Expanded patient assistance will ensure a greater number of patients receive comprehensive, compassionate care in a coordinated fashion from their initial visit through all follow-up appointments, as well as any other resources and support necessary for patients and their families.

WethanktheHutsonsfor their gift,whichwillexpandour teamscapabilities toprovidea coordinated, personalized experienceandworld-classcare forpatientsand their families affectedby neurological and mental health conditions,said Dr. AliRezai, executive chair of the Rockefeller Neuroscience Institute.

Rusty and Kimberly Hutson were both raised in Harrison County and graduated from Fairmont State University, where they earned degrees in accounting and nursing, respectively. Rusty Hutson worked in the banking industry for 13 years before co-founding Diversified Energy in 2001. He now serves as CEO of the company, building upon a family history in the oil and natural gas business that dates to the early 1900s.

Kimberly Hutson worked as a registered nurse before becoming a full-time mom to the couples four children. While the Hutsons reside in Birmingham, Alabama, they remain committed to the Mountain State. They have previously provided generous support for WVU athletics and business and nursing programs at Fairmont State.

The Hutsons gift was made through the WVU Foundation, the nonprofit organization that receives and administers private donations on behalf of the University, in conjunction withWVU Day of Giving.Alumni and friends made over 5,600 gifts totaling $15.5 millionto support the Universitys fifthDay of Giving on March 9.

-WVU-

cr/05/04/22

CONTACT: Cassie RiceCommunications SpecialistWVU Foundation}304-554-0217; crice@wvuf.org

Call 1-855-WVU-NEWS for the latest West Virginia University news and information from WVUToday.

Follow @WVUToday on Twitter.

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WVU Today | WVU experiential business learning, health care outreach and personalized nursing bolstered by couple's $1.8M gift - WVU Today

Neuroscience

Benefits of Exercise May Vary Greatly in Primary Mitochondrial Disease – Neuroscience News

Summary: The benefits of endurance exercise can vary based on the mutation types associated with primary mitochondrial disease, a new study reports.

Source: CHOP

Mitochondria serve as the main source of energy production in our cells, and endurance exercise is generally known to improve the function of mitochondria. However, the benefits of exercise in patients with primary mitochondrial diseases, which are heterogeneous and caused by a variety of genetic mutations, were largely unknown.

In a new study, researchers at Childrens Hospital of Philadelphia (CHOP) demonstrated that the benefits of endurance exercise can vary based on the type of mutation involved inmitochondrial disease, and while the benefits of exercise outweigh the risks, the mitochondrial genetic status of patients should be taken into consideration when recommending exercise as therapy.

The findings were published online today by theProceedings of the National Academy of Sciences.

Primary mitochondrial diseases represent the most prevalent inheritedmetabolic disorders, affecting approximately 1 in every 4,200 people. These disorders can be caused by hundreds of different mutations in the nuclear DNA (DNA within our cells) or mitochondrial DNA (mtDNA, or the DNA within the mitochondria within our cells).

Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders like diabetes or neurodegenerative disorders.

However, these recommendations were based on healthy people without primary mitochondrial disease. Therefore, researchers wanted to determine effectiveness for these patients and whether they are actually benefitting from endurance exercise.

There was not a consensus among clinicians who see patients with mitochondrial disease whether endurance exercise truly offers benefits, said Patrick Schaefer, Ph.D., a postdoctoral fellow at the Center for Mitochondrial and Epigenomic Medicine at CHOP and first author of the study.

Exercise helps create more mitochondria, but if those mitochondria still have the mutations associated with primary mitochondrial disease, there is a chance that exercise may put some patients at risk.

Because of the heterogeneity of primary mitochondrial disease among patients, the researchers used animal models to study five mutations responsible for the disease.

The goal of the study was to determine the relationship between mitochondrial mutations, endurance exercise response, and the underlying molecular pathways in these models with distinct mitochondrialmutations.

The study found that endurance exercise had different impacts on the models depending on the mutation involved. Exercise improved response in the model with the mtDNA ND6 mutation in complex I.

The model with a CO1 mutation affecting complex IV showed significantly fewer positive effects related to exercise, and the model with a ND5 complex 1 mutation did not respond to exercise at all. In the model that was deficient in nuclear DNA Ant1, endurance exercise actually worsened cardiomyopathy.

Additionally, the researchers were able to correlate the gene expression profile of skeletal muscle and heart in the model with exercise response and identifiedoxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways in exercise response, suggesting how the model might be adapted to study exercise responses in humans with primary mitochondrial disease.

Despite mixed responses of the models used in this study, the authors note that thebenefits of exerciseoutweigh the risks in most cases. However, the physical and mitochondrial status of the patient should be taken into account when recommending therapeutic exercises.

Additionally, the study could help researchers identify biomarkers and pathways to help predict the mitochondrial response toexerciseboth in mitochondrial patients and the healthy population harboring different mitochondrial haplogroups.

This work is of fundamental importance in demonstrating that individuals with different mitochondrial bioenergetics will respond differently toendurance exercise, said senior study author Douglas C. Wallace, Ph.D., director of the Center for Mitochondrial and Epigenomic Medicine at CHOP and the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases.

This is of broad relevance to individuals ranging from athletes to patients with mitochondrial disease, and everyone in between.

Author: Press OfficeSource: CHOPContact: Press Office CHOPImage: The image is in the public domain

Original Research: Closed access.Mitochondrial mutations alter endurance exercise response and determinants in mice by Patrick M. Schaefer et al. PNAS

Abstract

Mitochondrial mutations alter endurance exercise response and determinants in mice

Primary mitochondrial diseases (PMDs) are a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current therapeutic approaches are limited, although one approach has been exercise training.

Endurance exercise is known to improve mitochondrial function in heathy subjects and reduce risk for secondary metabolic disorders such as diabetes or neurodegenerative disorders. However, in PMDs the benefit of endurance exercise is unclear, and exercise might be beneficial for some mitochondrial disorders but contraindicated in others.

Here we investigate the effect of an endurance exercise regimen in mouse models for PMDs harboring distinct mitochondrial mutations.

We show that while an mtDNA ND6 mutation in complex I demonstrated improvement in response to exercise, mice with a CO1 mutation affecting complex IV showed significantly fewer positive effects, and mice with an ND5 complex I mutation did not respond to exercise at all. For mice deficient in the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually worsened the dilated cardiomyopathy.

Correlating the gene expression profile of skeletal muscle and heart with the physiologic exercise response identified oxidative phosphorylation, amino acid metabolism, matrisome (extracellular matrix [ECM]) structure, and cell cycle regulation as key pathways in the exercise response. This emphasizes the crucial role of mitochondria in determining the exercise capacity and exercise response.

Consequently, the benefit of endurance exercise in PMDs strongly depends on the underlying mutation, although our results suggest a general beneficial effect.

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Benefits of Exercise May Vary Greatly in Primary Mitochondrial Disease - Neuroscience News

Neuroscience

New Insights on Gene Activity and Addiction – Neuroscience News

Summary: Study sheds new light on the role dopamine plays in addiction and gene activity in neurons.

Source: North Carolina State University

Researchers at North Carolina State University have demonstrated that neuron-like cells derived from human stem cells can serve as a model for studying changes in the nervous system associated with addiction.

The work sheds light on the effect of dopamine on gene activity in neurons, and offers a blueprint for related research moving forward.

It is extremely difficult to study how addiction changes the brain at acellular levelin humansnobody wants to experiment on somebodys brain, says Albert Keung, corresponding author of the study and an assistant professor of chemical and biomolecular engineering at NC State.

What weve done here demonstrates that we can gain a deep understanding of those cellular responses using neuron-like cells derived fromhuman stem cells.

At issue is how cells in ournervous systemrespond to drugs that are associated with substance abuse and addiction. Our bodies produce a neurotransmitter calleddopamine. Its associated with feelings, such as pleasure, that are related to motivation and reward.

When neuronal cells in the brains reward pathway are exposed to dopamine, the cells activate a specific suite of genes, triggering the feelings of reward that can make people feel good. Many drugsfrom alcohol and nicotine to opioids and cocainecause the body to produce higher levels of dopamine.

In experiments using rodents, researchers have shown that when relevant neuronal cells are exposed to high levels of dopamine for an extended period of time, they become desensitizedmeaning the cells gene activation is less pronounced in response to the dopamine, Keung says.

This is called gene desensitization. However, until now, it hasnt been possible to do an experimental study using human neuronal cells.

Our work here is the first experimental study to demonstrate gene desensitization in humanneuronal cells, specifically in response to dopamine, says Ryan Tam, first author of the study and a Ph.D. student at NC State. We dont have to infer that it is happening inhuman cells; we can show that it is happening in human cells.

In their study, Tam and Keung exposed neuron-like cells derived from human stem cells to varying levels of dopamine for varying periods of time. The researchers found that when cells were exposed to high levels of dopamine for an extended period of time, the relevant reward genes became significantly less responsive.

This is an interesting finding, but its also a proof of concept study, Tam says. Weve demonstrated that gene desensitization to dopamine occurs in human cells, but there is still a lot we dont know about the nature of the relationship between dopamine and gene desensitization.

For example, could higher levels of dopamine cause desensitization at shorter time scales? Or could lower levels of dopamine cause desensitization at longer time scales? Are there threshold levels, or is there some sort of linear relationship? How might the presence of other neurotransmitters or bioactive chemicals affect these responses?

Those are good questions, which future research could address, says Keung. And weve demonstrated that these neuron-like cells derived from human stem cells are a good model for conducting that research.

Author: Matt ShipmanSource: North Carolina State UniversityContact: Matt Shipman North Carolina State UniversityImage: The image is credited to Ryan Tam, NC State University

Original Research: Open access.Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization by Ryan W. Tam et al. Cells

AbstractHuman Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization

Gene desensitization in response to a repeated stimulus is a complex phenotype important across homeostatic and disease processes, including addiction, learning, and memory.

These complex phenotypes are being characterized and connected to important physiologically relevant functions in rodent systems but are difficult to capture in human models where even acute responses to important neurotransmitters are understudied.

Here through transcriptomic analysis, we map the dynamic responses of human stem cell-derived medium spiny neuron-like cells (hMSN-like cells) to dopamine.

Furthermore, we show that these human neurons can reflect and capture cellular desensitization to chronic versus acute administration of dopamine. These human cells are further able to capture complex receptor crosstalk in response to the pharmacological perturbations of distinct dopamine receptor subtypes.

This study demonstrates the potential utility and remaining challenges of using human stem cell-derived neurons to capture and study the complex dynamic mechanisms of the brain.

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New Insights on Gene Activity and Addiction - Neuroscience News