NS/ Spiral-shaped signals for organizing brain activity discovered
Neuroscience biweekly vol. 87, 7th June — 21st June
TL;DR
- The University of Sydney and Fudan University scientists have discovered human brain signals traveling across the outer layer of neural tissue that naturally arrange themselves to resemble swirling spirals. The research, published in Nature Human Behaviour, indicates these ubiquitous spirals, which are brain signals observed on the cortex during both resting and cognitive states, help organize brain activity and cognitive processing.
- New research led by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in partnership with ADM Protexin, has shown improvements in depression and anxiety scores among individuals supplementing with probiotics alongside standard antidepressant medication.
- Researchers of the Human Brain Project have used a model-based approach to identify the brain circuits implicated in consciousness. The results of the study, a collaboration between Pompeu Fabra University in Barcelona and the University of Liège, have been published in the journal Human Brain Mapping. The team studied the propagation of signals in models of the brain of patients with disorders of consciousness (DoC), identifying two relevant circuits in the posterior cortical region and the thalamic-frontotemporal region. The results bring more understanding of the inner workings of brain networks and could improve diagnosis and even provide treatment targets for people suffering from DoC.
- Scientists have identified the neurons that are activated when perceiving others, as well as the neurons that represent valuable information associated with others in the CA1 region of the hippocampus using a novel social recognition experiment.
- Researchers have created one of the most detailed 3D images of the synapse, the important juncture where neurons communicate with each other through an exchange of chemical signals. These nanometer-scale models will help scientists better understand and study neurodegenerative diseases such as Huntington’s disease and schizophrenia.
- In a pioneering study involving serial entrepreneurs and managers, a multidisciplinary research team, combining entrepreneurship researchers and brain specialists, found evidence of increased neuronal connectivity in the brains of entrepreneurs, which may contribute to distinct cognitive attributes.
- New research shines a light on how parents who talk more to their infants improve their children’s brain development. Scientists used imaging and audio recordings to link early language skills to caregiver speech, delivering an affirming message that parents can greatly influence their child’s linguistic growth in ways that are trackable in brain scans.
- A new study offers an explanation for why light-to-moderate alcohol consumption may be associated with lower risk of heart disease. For the first time, researchers found that alcohol, in light to moderate quantities, was associated with long-term reductions in stress signaling in the brain.
- Nutrition is an important part of any top athlete’s training program. And now, a new study proposes that supplementing the diet of athletes with colorful fruits and vegetables could improve their visual range. The paper examines how a group of plant compounds that build up in the retina, known as macular pigments, work to improve eye health and functional vision.
- And more!
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The latest news and research
Interacting spiral wave patterns underlie complex brain dynamics and are related to cognitive processing
by Xu Y, Long X, Feng J, Gong P. in Nat Hum Behavior
The University of Sydney and Fudan University scientists have discovered human brain signals travelling across the outer layer of neural tissue that naturally arrange themselves to resemble swirling spirals. The research, published in Nature Human Behaviour, indicates these ubiquitous spirals, which are brain signals observed on the cortex during both resting and cognitive states, help organize brain activity and cognitive processing.
Senior author Associate Professor Pulin Gong, from the School of Physics in the Faculty of Science, said the discovery could have the potential to advance powerful computing machines inspired by the intricate workings of the human brain.
The discovery opens up new avenues for understanding how the brain works and provides valuable insights into the fundamental functions of the human brain. It could help medical researchers understand the effects of brain diseases, such as dementia, by examining the role they play.
“Our study suggests that gaining insights into how the spirals are related to cognitive processing could significantly enhance our understanding of the dynamics and functions of the brain,” said Associate Professor Gong, who is a member of the Complex Systems research group in Physics.
“These spiral patterns exhibit intricate and complex dynamics, moving across the brain’s surface while rotating around central points known as phase singularities.
“Much like vortices act in turbulence, the spirals engage in intricate interactions, playing a crucial role in organising the brain’s complex activities.
“The intricate interactions among multiple co-existing spirals could allow neural computations to be conducted in a distributed and parallel manner, leading to remarkable computational efficiency.”
PhD student Yiben Xu, the lead author of the research from the School of Physics, said the location of the spirals on the cortex could allow them to connect activity in different sections, or networks, of the brain — acting as a bridge of communication. Many of the spirals are large enough to cover multiple networks.
The cortex of the brain, also known as the cerebral cortex, is the outermost layer of the brain that is responsible for many complex cognitive functions, including perception, memory, attention, language and consciousness.
“One key characteristic of these brain spirals is that they often emerge at the boundaries that separate different functional networks in the brain,” Mr Xu said. “Through their rotational motion, they effectively coordinate the flow of activity between these networks.
“In our research we observed that these interacting brain spirals allow for flexible reconfiguration of brain activity during various tasks involving natural language processing and working memory, which they achieve by changing their rotational directions.”
The scientists gathered their findings from functional magnetic resonance imaging (fMRI) brain scans of 100 young adults, which they analysed by adapting methods used to understand complex wave patterns in turbulence.
Neuroscience has traditionally focused on interactions between neurons to understand brain function. There is a growing area of science looking at larger processes within the brain to help us understand its mysteries.
“By unravelling the mysteries of brain activity and uncovering the mechanisms governing its coordination, we are moving closer to unlocking the full potential of understanding cognition and brain function,” Associate Professor Gong said.
Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial
by Nikolova VL, Cleare AJ, Young AH, Stone JM in JAMA Psychiatry
New research led by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in partnership with ADM Protexin, has shown improvements in depression and anxiety scores among individuals supplementing with probiotics alongside standard antidepressant medication.
Researchers have found evidence that supplementing the diet with a probiotic blend containing 14 strains of bacteria can help individuals who are being treated for major depressive disorder with antidepressants. Published in JAMA Psychiatry, the study demonstrated the potential of probiotic supplementation to support improvements in multiple depression and anxiety scores over an eight-week period.
The pilot study is one of the first trials in a Western population to show both good tolerability of probiotics and positive effects on mental health in adults with depression currently taking antidepressants. According to the researchers leading the study, the results provide a strong basis to further investigate the benefits of this probiotic food supplement for supporting mood and mental health in a larger trial.
There is increasing evidence that the gut microbiota (the vast and dynamic community of microorganisms inhabiting the gut) has a role to play in the regulation of mood. The study was a double-blind, randomised placebo-controlled study, designed as an initial exploration of whether improving gut health through the use of probiotics — supplements containing beneficial bacteria — could act as a new pathway for supporting mood and mental health.
Non- or partial response to antidepressants is a huge problem and this study is an important first step in exploring the therapeutic potential of probiotics as a treatment for depression. We found that probiotics were an acceptable and tolerable supplement in people already taking antidepressant medications. This now paves the way for studies looking at whether we see these beneficial effects of probiotics on depression and anxiety in larger populations of patients.
Professor James Stone, the study’s senior investigator who began the work at King’s IoPPN and is now at Brighton and Sussex Medical School
In this pilot trial, 49 adults with diagnosed major depressive disorder and with an incomplete response to prescription antidepressants were provided with a widely available, proprietary 14 strain blend probiotic supplement or an identical placebo (24 receiving the probiotic). Over the course of eight weeks, both groups demonstrated improvement in their symptoms, but greater improvements were seen in the probiotic group from week four onwards. Meaningful reported improvements were seen, measured against gold standard rating scales for depression and anxiety.
Dr Richard Day, VP of Medical Affairs at ADM said, “According to the World Health Organisation, an estimated 5% of adults suffer from depression, with a significant number failing to respond completely to standard treatment options. This trial is one of the few clinical studies to assess the benefits of supplementing the diet with probiotics alongside standard of care antidepressant medication. These exciting results add to our understanding of the link between the gut microbiome and mental health.”
Whole-brain analyses indicate the impairment of posterior integration and thalamo-frontotemporal broadcasting in disorders of consciousness
by Panda R, López-González A, Gilson M, et al. in Human Brain Mapping
Researchers of the Human Brain Project have used a model-based approach to identify the brain circuits implicated in consciousness. The results of the study, a collaboration between Pompeu Fabra University in Barcelona and University of Liège, have been published in the journal Human Brain Mapping. The team studied the propagation of signals in models of the brain of patients with disorders of consciousness (DoC), identifying two relevant circuits in the posterior cortical region and the thalamo-frontotemporal region. The results bring more understanding of the inner workings of brain networks and could improve diagnosis and even provide treatment targets for people suffering from DoC.
Currently, patients with DoC are classified into several categories (coma, unresponsive wakefulness syndrome and minimally conscious state) which describe their overall consciousness and awareness.
“The diagnosis is mainly response-based: the doctor sits down with the patient and assesses their response to stimuli” explains Jitka Annen from the University of Liège.
“However, this may not correspond to their underlying brain activity — patients with high activity may still be unable to react. It’s a heterogenous group. We wanted to go a step beyond assessment and classification based on neuroimaging and instead look at the flow of information in their brains, to find common patterns associated with consciousness”.
The researchers focused on two DoC groups — unresponsive wakefulness syndrome (previously known as vegetative state) and minimally conscious state. After collecting fMRI data from each patient during resting state (i.e., patients were awake but no particular task was provided), they looked at spontaneous and model-based perturbation of brain activity captured by the blood flow, such as signals and peaks.
“Based on spontaneous peaks of activity, we evaluated the personalised connectivity of each patient’s brain, which can tell us how likely a signal is to travel from one point to the other” says Gorka Zamora-López from Pompeu Fabra. “After we constructed a patient-specific computational model of their propagation patterns, we then trigger a signal in the model and see how the brain reacts. In particular we look for which areas are more likely to respond to a signal; which areas are more likely to propagate it. Basically, we look at whether an area acts as influencer or influenced”.
A marked distinction arises between the unresponsive wakefulness syndrome group and minimally conscious state group, with the former not displaying activity in identifiable circuits.
“The key difference is that in patients with unresponsive wakefulness syndrome no region of the brain seems embedded in a functional network, they all display equally low activation. Meanwhile, distinct regions and circuits pop out in the brain models of people in minimally conscious state: the thalamo-frontotemporal region when broadcasting signals, and the posterior cortical region when receiving them” adds Rajanikant Panda of the University of Liège.
These findings shed new light on disorders of consciousness, and could lead to a more defined understanding of the mechanisms based on brain activity rather than behavioral responses.
“I believe these results can potentially guide the clinicians to better understand what is going wrong in the information exchange and thus look for ways to reactivate those circuits” concludes Zamora-López.
Dynamic and stable hippocampal representations of social identity and reward expectation support associative social memory in male mice
by Eunji Kong, Kyu-Hee Lee, Jongrok Do, Pilhan Kim, Doyun Lee in Nature Communications
Researchers from the Center for Cognition and Sociality (CCS) within the Institute for Basic Science (IBS) recently announced the discovery of neurons that allow us to recognize others. The research team discovered that the neurons that deal with the information associated with different individuals are located in the CA1 region of the hippocampus.
Social animals, including humans, constantly engage in interactions with others. In this process, the ability to recognize the identity of the social counterpart, retrieve relevant information about them from memory, and update it from the current interaction is critical for establishing social relationships. However, there has been limited research on how these processes occur in the brain.
In order to answer this question, past efforts mostly focused on mouse brain studies, particularly in the hippocampus. The hippocampus was thought to be the answer, since it is a brain structure that is well-known to be responsible for memory formation. Within the hippocampus, the Cornu Ammonis (CA) fields, which are numbered CA1, to CA3, are involved in various functions related to memory and spatial processing and were hence key research interests.
So far, the mouse studies on the neural mechanisms of individual recognition mainly focused on the CA2 region of the hippocampus. However, previous studies have used behavioral experiments that only involve distinguishing unfamiliar mice from familiar mice, making it difficult to interpret whether the results reflect the animal’s ability to perceive or truly recognize individual characteristics.
In this study, the IBS-CCS research team developed a new behavioral paradigm using mice to better investigate their ability to recognize other individuals. Their new method involved having the subject mouse associate specific individual mice with rewards and studying their behavior after encountering reward-associated individuals and not associated individuals.
Specifically, two mice were immobilized on a spinning disk and were randomly presented to a subject mouse, which would recognize the neighbor through scent. Water is then supplied from the device to the subject mouse as a reward when licking in response to the reward-associated mouse, but not another. The researchers tried to determine whether the subject mouse could discriminate against different individuals and analyzed the brain cell activity during the experiment.
The stimulus mice on the spinning disk were male littermates and the subject mice were already familiar with the stimulus mice. This means that the subject mice distinguished between stimulus mice solely according to the unique characteristics of the stimulus mice, suggesting the high reliability of the experimental results.
Using this behavioral paradigm, the researchers clearly demonstrated that the dorsal CA1 region of the hippocampus plays an essential role in individual recognition. For example, when the hippocampal CA1 region is suppressed using a neuroinhibitor, the subject mouse was unable to distinguish its neighbor. Also by using a two-photon imaging technique that allows real-time observation of neural cell activity in the deep regions of the brain, the IBS-CCS team even identified the specific neuronal cells in the hippocampal CA1 region that is responsible for the recognition of individual mice.
This was an interesting addition to previous findings, which have proposed the dorsal CA2 region of the hippocampus to be the important brain area for social memory while reporting that the dorsal CA1 region does not play a significant role.
Furthermore, researchers in the past believed that social memories in rodents only last for a short period of time and that they do not form long-term memories about individual subjects. However, the latest study by the IBS-CCS has demonstrated that long-term memories about individuals can indeed be formed in mice.
Dr. LEE Doyun who led this research stated, “We have revealed for the first time how value information about others obtained through positive or negative interactions with them is represented and stored in our brains. Furthermore, this provides significant insights into understanding the role of our brains in building and developing human relationships through various social interactions.”
Beyond that, the researchers have also revealed the presence of specific neurons in the subject mouse’s hippocampal CA1 region that process positive information associated with different individual mice. An important part of forming a social relationship is assigning a positive or negative value to a social encounter with another individual and updating that value. For example, just as it is essential to develop a friendship with a particular individual, it is essential to evaluate how enjoyable and rewarding it was to interact with them.
These specific CA1 neurons were found to be responsive when encountering reward-associated individuals. However, such reward expectation responses were not observed when the subject was exposed to odors that are unrelated to social activity, such as citral or butanol. These findings indicate that the hippocampal CA1 region plays a selectively important role in the formation of associative social memories.
It is hoped that this new discovery can lead to a potential solution for the treatment of various brain disorders that cause difficulty in forming social relationships.
“Our results could be utilized to understand and propose treatment methods for mental disorders such as autism, which exhibit abnormalities in brain functions involved in processing memories and related information about others,” explains Dr. Lee.
Astrocytic engagement of the corticostriatal synaptic cleft is disrupted in a mouse model of Huntington’s disease
by Carlos Benitez Villanueva, Hans J. T. Stephensen, Rajmund Mokso, Abdellatif Benraiss, Jon Sporring, Steven A. Goldman in Proceedings of the National Academy of Sciences
Scientists have created one of the most detailed 3D images of the synapse, the important juncture where neurons communicate with each other through an exchange of chemical signals. These nanometer scale models will help scientists better understand and study neurodegenerative diseases such as Huntington’s disease and schizophrenia.
The new study appears in the journal PNAS and was authored by a team led by Steve Goldman, MD, PhD, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen. The findings represent a significant technical achievement that allows researchers to study the different cells that converge at individual synapses at a level of detail not previously achievable.
“It is one thing to understand the structure of the synapse from the literature, but it is another to see the precise geometry of interactions between individual cells with your own eyes,” said Abdellatif Benraiss, PhD, a research associate professor in the Center for Translational Neuromedicine and co-author of the study. “The ability to measure these extremely small environments is a young field, and holds the potential to advance our understanding of a number of neurodegenerative and neuropsychiatric diseases in which synaptic function is disturbed.”
The researchers used the new technique to compare the brains of healthy mice to mice carrying the mutant gene that causes Huntington’s disease. Prior research in Goldman’s lab has shown that dysfunctional astrocytes play a key role in the disease. Astrocytes are members of a family of support cells in the brain called glia, and help maintain the proper chemical environment at the synapse.
The researchers focused on synapses that involve medium spiny motor neurons, the progressive loss of these cells is a hallmark of Huntington’s disease. The researchers first had to identify synapses hidden within the tangle of the three different cells that converge at the site: the pre-synaptic axon from a distant neuron; its target, the post-synaptic medium spiny motor neuron; and the fiber processes of a neighboring astrocyte.
To do so, the investigators employed viruses to assign separate fluorescent tags to the axons, motor neurons, and astrocytes. They then removed the brains, imaged the areas of interest by multiphoton microscopy, and used a technique called infrared branding that employs lasers to create reference points in the brain tissue, which allowed the researchers to later relocate the cells of interest.
The team then examined the brain tissue using a serial block-face scanning electron microscope located at the University of Copenhagen, a research tool created to study the smallest structures of the brain. The device uses a diamond knife to serially remove and image ultrathin slices of brain tissue, creating 3D, nanometer scale models of the labeled cells and their interactions at the synapse.
“The models reveal the geometry and structural relationships between astrocytes and their partnered synapses, which is important because these cells must interact in a specific manner at the synapse,” said Carlos Benitez Villanueva, PhD, senior associate in Center for Translational Neuromedicine and first author of the study. “This approach gives us the ability to measure and describe the geometry of the synaptic environment, and to do so as a function of glial disease.”
In the brains of healthy mice, the team observed that astrocytic processes engaged with and completely enveloped the space around the disk-shaped synapse, creating a tight bond. In contrast, the astrocytes in Huntington’s mice were not as effective in investing or sequestering the synapse, leaving large gaps. This structural flaw allows potassium and glutamate — chemicals that regulate communication between cells — to leak from the synapse, potentially disrupting normal cell-cell communication.
Astrocyte dysfunction been linked with other conditions, including schizophrenia, amyotrophic lateral sclerosis, and frontotemporal dementias. The researchers believe this technique could greatly improve our understanding of the precise structural basis for those diseases. In particular, they point out that this technique might be used to evaluate the effectiveness of cell replacement strategies, which replace sick glial cells with healthy ones, for treating these diseases.
Advancing (Neuro)Entrepreneurship Cognition Research Through Resting-State fMRI: A Methodological Brief
by Frédéric Ooms, Jitka Annen, Rajanikant Panda, Paul Meunier, Luaba Tshibanda, Steven Laureys, Jeffrey M. Pollack, Bernard Surlemont in Entrepreneurship Theory and Practice
In a pioneering study involving serial entrepreneurs and managers, a multidisciplinary research team led by HEC — School of Management at the University of Liège and Liège University Hospital (CHU Liège), combining entrepreneurship researchers and brain specialists, found evidence of increased neuronal connectivity in the brains of entrepreneurs, which may contribute to distinct cognitive attributes.
Using resting-state functional magnetic resonance imaging (rs-fMRI), the study showed that serial entrepreneurs have higher connectivity between the right insula (associated with cognitive flexibility) and the anterior prefrontal cortex (a key region for exploratory choices), compared to their fellow managers. These results, published in the journal Entrepreneurship Theory and Practice, suggest that serial entrepreneurs possess greater cognitive flexibility, enabling them to alternate effectively between exploration and exploitation, a balance that is crucial to their success.
Unlike the traditional fMRI approach based on tasks submitted to the subject, the rs-fMRI on which this study is based observes the brain at rest, in the absence of cognitive tasks or presentation of stimuli, which constitutes an innovative approach to improving understanding of the entrepreneurial mind. Forty people, entrepreneurs and managers, took part in the study.
“This study represents an important advance in our understanding of the entrepreneurial mind. It highlights the potential of neuroscience and how this approach complements the traditional tools used to study entrepreneurial cognition. By highlighting the difference in cognitive flexibility, it also offers a new perspective to inform the design of training or professional development programmes aimed at improving the cognitive flexibility and entrepreneurial spirit of individuals within various organisations,” explains Frédéric Ooms, researcher and Assistant Professor in management and entrepreneurship (HEC — ULiège School of Management), first author of the publication, based on the results of his PhD thesis on entrepreneurial cognitive flexibility presented in April 2023.
“In a world of rapid and unpredictable change, organisations need to cultivate an entrepreneurial mindset and foster cognitive flexibility within their teams, qualities recognised by the OECD as a 21st century challenge,” points out Professor Bernard Surlemont, Professor of Entrepreneurship at ULiège (HEC Liège).
Language exposure during infancy is negatively associated with white matter microstructure in the arcuate fasciculus
by Katiana A. Estrada, Sharnya Govindaraj, Hervé Abdi, Luke E. Moraglia, Jason J. Wolff, Shoba Sreenath Meera, Stephen R. Dager, Robert C. McKinstry, Martin A. Styner, Lonnie Zwaigenbaum, Joseph Piven, Meghan R. Swanson in Developmental Cognitive Neuroscience
A team led by a University of Texas at Dallas neurodevelopment researcher has uncovered some of the most conclusive evidence yet that parents who talk more to their infants improve their babies’ brain development.
The researchers used MRI and audio recordings to demonstrate that caregiver speech is associated with infant brain development in ways that improve long-term language progress. Dr. Meghan Swanson, assistant professor of psychology in the School of Behavioral and Brain Sciences, is corresponding author of the study, which was published online April 11 and in the June print edition of Developmental Cognitive Neuroscience.
“This paper is a step toward understanding why children who hear more words go on to have better language skills and what process facilitates that mechanism,” Swanson said. “Ours is one of two new papers that are the first to show links between caregiver speech and how the brain’s white matter develops.”
White matter in the brain facilitates communication between various gray matter regions, where information processing takes place in the brain.
The research included 52 infants from the Infant Brain Imaging Study (IBIS), a National Institutes of Health-funded Autism Center of Excellence project involving eight universities in the U.S. and Canada and clinical sites in Seattle, Philadelphia, St. Louis, Minneapolis, and Chapel Hill, North Carolina. Home language recordings were collected when children were 9 months old and again six months later, and MRIs were performed at 3 months old and 6 months old, and at ages 1 and 2.
“This timing of home recordings was chosen because it straddles the emergence of words,” Swanson said. “We wanted to capture both this prelinguistic, babbling time frame, as well as a point after or near the emergence of talking.”
It’s long been known that an infant’s home environment — especially the quality of caregiver speech — directly influences language acquisition, but the mechanisms behind this are unclear. Swanson’s team imaged several areas of the brain’s white matter, focusing on developing neurological pathways.
“The arcuate fasciculus is the fiber tract that everyone in neurobiology courses learns is essential to producing and understanding language, but that finding is based on adult brains,” Swanson said. “In these children, we looked at other potentially meaningful fiber tracts as well, including the uncinate fasciculus, which has been linked to learning and memory.”
The researchers used the images to measure fractional anisotropy (FA). This metric for the freedom or restriction of water movement in the brain is used as a proxy for the progress of white matter development.
“As a fiber track matures, water movement becomes more restricted, and the brain’s structure becomes more coherent,” Swanson said. “Because babies aren’t born with highly specialized brains, one might expect that networks that support a given cognitive skill start out more diffuse and then become more specialized.”
Swanson’s team found that infants who heard more words had lower FA values, indicating that the structure of their white matter was slower to develop. The children went on to have better linguistic performance when they began to talk.
The study’s results align with other recent research showing that slower maturation of white matter confers a cognitive advantage.
“As a brain matures, it becomes less plastic — networks get set in place. But from a neurobiological standpoint, infancy is unlike any other time. An infant brain seems to rely on a prolonged period of plasticity to learn certain skills,” Swanson said. “The results show a clear, striking negative association between FA and child vocalization.”
Sharnya Govindaraj, co-first author of the paper, a cognition and neuroscience doctoral student and a member of Swanson’s Baby Brain Lab, said at first she was surprised by the results.
“We initially didn’t know how to interpret these negative associations that seemed very counterintuitive. The whole concept of neuroplasticity and absorbing new knowledge had to fall into place,” she said. “Which ability we’re looking at also matters a great deal, because something like vision matures much earlier than language.”
As the parent of a toddler in a bilingual household, Swanson was curious about how this relationship functions for infants exposed to more than one language.
“Raising a bilingual child, it is remarkable how she is not confused by languages, and she knows who she can use which language with,” Swanson said.
Swanson said she also has gained a deeper level of appreciation and gratitude for what she, as a researcher, asks parents in her studies to do.
“When participants sign up, I’m asking them to commit to a year and a half,” she said. “Because of the commitment of all the parents in prior studies, I and others have the knowledge that allows us to communicate with our children in a way that supports their development.”
Swanson said the take-home message is that parents have the power to help their children develop.
“This work highlights parents as change agents in their children’s lives, with the potential to have enormous protective effects,” Swanson said. “I hope our work empowers parents with the knowledge and skills to support their children as best they can.”
Anticipation of Appetitive Operant Action Induces Sustained Dopamine Release in the Nucleus Accumbens
by Jessica Goedhoop, Tara Arbab, Ingo Willuhn in The Journal of Neuroscience
A new study from the Netherlands Institute for Neuroscience brings together two schools of thought on the function of the neurotransmitter dopamine: one saying that dopamine provides a learning signal, the other saying that dopamine drives motivation. ‘But it is probably both’, says Ingo Willuhn.
It is well-known that the dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. This can be investigated using either Pavlovian and operant conditioning experiments. Pavlovian conditioning describes how your brain makes an association between two situations or stimuli that previously seemed unrelated. A famous example is Pavlov’s experiment, where a dog heard a sound before receiving food. After several such pairings of the sound with food delivery, the sound alone began to cause the dog to salivate. Operant conditioning, or instrumental learning, differs from this in that the behavior of an individual is important to earn a food reward. Meaning that the individual after hearing a sound, has to perform a so-called operant action to receive the reward. In animal experiments, such a operant response is often the pressing of a lever.
In the final PhD paper of Jessica Goedhoop in collaboration with Tara Arbab and Ingo Willuhn from the Netherlands Institute for Neuroscience, they take a closer look at the role of dopamine signaling in learning and motivation. The team directly compared the two conditioning paradigms: male rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. During the experiments a cue light was illuminated for a duration of 5 seconds. For the Pavlovian group, a food pellet was delivered into the reward magazine directly after the cue light turned off. For the operant conditioning group, turning off the cue light was followed by extension of the lever below the cue light into the operant box. The lever was retracted after one lever press, which immediately resulted in the delivery of one food pellet reward into the food magazine. If there was no lever press within 5 seconds after lever extension, the lever was retracted and no reward was delivered.
Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire 5-second cue presentation (throughout cue presentation and before lever press). This dopamine sustainment was observed reliably and consistently throughout systematic manipulation of experimental parameters and behavioral training. Therefore, the researchers believe that sustained dopamine levels may be an intermediate between learning and action, conceptually related to the motivation to generate a reward-achieving action.
Ingo Willuhn: ‘There have been a lot of studies on dopamine. We have a decent idea of when dopamine is released in the brain, but there is still lots of discussion on what the precise variables are that determine such dopamine signaling. Essentially discussion on what dopamine “means.” To investigate this, scientists usually perform either Pavlovian or operant conditioning experiments. But they test slightly different things. Both have to do with learning an association between a neutral stimulus and a reward. But operant conditioning requires the motivation to perform an action in addition to that (to earn the reward). Therefore, we compared the two types of conditioning in the same experiment.’
‘Our results bring together the two camps of scientists that often battle with each other: one says that dopamine is a so-called reward-prediction error signal, meaning that dopamine is released when something better than expected happens, and is suppressed when something worse than expected happens. It is a learning (or teaching) signal. The other camp says that this is not true. They say that dopamine has something to do with motivation. Increased dopamine release will invigorate the subjects and they work harder to get the reward. There have been a few attempts in the past to bring these two camps together, but there is still need for more knowledge on the subject.’
‘What we saw in our study is that only in the operant-learning task dopamine levels stayed high. It seems that the motivation is encoded in this plateau. Reward prediction is the initial dopamine peak, but how much the signal stays up, reflects motivation. Thus, our paper suggests that there is a possibility that dopamine is involved in both, learning and motivation. The next steps will be to get more details out of this. We need to replicate the experiments and make them more sophisticated. The more sophisticated you make it, the more precise our predictions have to be. We are going to build on it and see whether it still holds up.’
‘Dopamine is not only involved in everyday life but also in disorders such as addiction, Parkinson’s disease, and schizophrenia. Because of the two camps existing, there is disagreement about what happens exactly. For example, some researchers say that when addicts take drugs dopamine release increases and as a consequence all the environmental cues become more meaningful. Addicts learn that these cues are associated with the drug and they take more and more drug, because they are constantly reminded of the drug everywhere. In this view, addiction is misguided learning. Other researchers would say that motivation to take the drug intensifies with more frequent drug intake, because the drug elevates dopamine release. This study indicates that it may be both. Depending on the precise timing, both systems could be the driver, and both could be involved.’
Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk
by Kenechukwu Mezue, Michael T. Osborne, Shady Abohashem, Hadil Zureigat, Charbel Gharios, Simran S. Grewal, Azar Radfar, Alexander Cardeiro, Taimur Abbasi, Karmel W. Choi, Zahi A. Fayad, Jordan W. Smoller, Rachel Rosovsky, Lisa Shin, Roger Pitman, Ahmed Tawakol in Journal of the American College of Cardiology
A new study led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, offers an explanation for why light-to-moderate alcohol consumption may be associated with lower risk of heart disease. For the first time, researchers found that alcohol, in light to moderate quantities, was associated with long-term reductions in stress signaling in the brain. This impact on the brain’s stress systems appeared to significantly account for the reductions in cardiovascular events seen in light to moderate drinkers participating in the study. Findings are published in the Journal of the American College of Cardiology.
“We are not advocating the use of alcohol to reduce the risk of heart attacks or strokes because of other concerning effects of alcohol on health,” says senior author and cardiologist Ahmed Tawakol, MD, co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital. “We wanted to understand how light to moderate drinking reduces cardiovascular disease, as demonstrated by multiple other studies. And if we could find the mechanism, the goal would be to find other approaches that could replicate or induce alcohol’s protective cardiac effects without the adverse impacts of alcohol.”
Previous epidemiological studies have suggested that light to moderate alcohol consumption (1 drink per day for women and 1 to 2 drinks per day for men) is associated with a lower risk of cardiovascular disease. But it was unknown whether alcohol was inducing cardiovascular benefits, or whether light/moderate drinkers’ health behaviors, socioeconomic status, or other factors protected their hearts.
The study, led by K Mezue and M Osborne, included more than 50,000 individuals enrolled in the Mass General Brigham Biobank. The first part of the study evaluated the relationship between light/moderate alcohol consumption and major adverse cardiovascular events after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic confounders. The researchers found that light/moderate alcohol consumption was associated with a substantial reduction in the risk of cardiovascular disease events, even after accounting for those other factors.
Next, they studied a subset of 754 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light/moderate alcohol consumption on resting stress-related neural network activity.
The brain imaging showed reduced stress signaling in the amygdala, the brain region associated with stress responses, in individuals who were light to moderate drinkers compared to those who abstained from alcohol or who drank little. And when the investigators looked at these individuals’ history of cardiovascular events, they found fewer heart attacks and strokes in light to moderate drinkers. “We found that the brain changes in light to moderate drinkers explained a significant portion of the protective cardiac effects,” says Tawakol.
It’s long been known that alcohol reduces the amygdala’s reactivity to threatening stimuli while individuals are drinking. The current study is the first to indicate that light to moderate alcohol consumption has longer-term neurobiological effects in dampening activity in the amygdala, which may have a significant downstream impact on the cardiovascular system.
“When the amygdala is too alert and vigilant, the sympathetic nervous system is heightened, which drives up blood pressure and increases heart rate, and triggers the release of inflammatory cells,” explains Tawakol. “If the stress is chronic, the result is hypertension, increased inflammation, and a substantial risk of obesity, diabetes, and cardiovascular disease.”
Finally, the investigators examined whether light/moderate alcohol would be even more effective at reducing heart attacks and strokes in people who are prone to a chronically higher stress response, such as those with a history of significant anxiety. They found that, within the 50,000-patient sample, light to moderate drinking was associated with nearly double the cardiac-protective effect in individuals with a history of anxiety compared with others.
Yet while light/moderate drinkers lowered their risk for cardiovascular disease, the study also showed that any amount of alcohol increases the risk of cancer. And at higher amounts of alcohol consumption — more than 14 drinks a week — heart attack risk started to increase while overall brain activity started to decrease (which may be associated with adverse cognitive health).
The authors concluded that research should focus on finding new interventions that reduce the brain’s stress activity without the deleterious effects of alcohol. The research team is currently studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacological therapies on stress-associated neural networks and how they might induce cardiovascular benefits.
A Dietary Strategy for Optimizing the Visual Range of Athletes
by Jacob B. Harth, Lisa M. Renzi-Hammond, Billy R. Hammond in Exercise and Sport Sciences Reviews
Nutrition is an important part of any top athlete’s training program. And now, a new study by researchers from the University of Georgia proposes that supplementing the diet of athletes with colorful fruits and vegetables could improve their visual range.
The paper, which was published in Exercise and Sport Sciences Reviews, examines how a group of plant compounds that build up in the retina, known as macular pigments, work to improve eye health and functional vision.
Previous studies done by UGA researchers Billy R. Hammond and Lisa Renzi-Hammond have shown that eating foods like dark leafy greens or yellow and orange vegetables, which contain high levels of the plant compounds lutein and zeaxanthin, improves eye and brain health.
“A lot of the research into macular lutein and zeaxanthin has focused on health benefits, but from a functional perspective, higher concentrations of these plant pigments improve many aspects of visual and cognitive ability. In this paper, we discuss their ability to improve vision in the far distance or visual range,” said lead author Jack Harth, a doctoral candidate in UGA’s College of Public Health.
Visual range, or how well a person can see a target clearly over distance, is a critical asset for top athletes in almost any sport.
The reason why objects get harder to see and appear fuzzier the farther they are from our eyes is thanks in part to the effects of blue light.
“From a center fielder’s perspective, if that ball’s coming up in the air, it will be seen against a background of bright blue sky, or against a gray background if it’s a cloudy day. Either way, the target is obscured by atmospheric interference coming into that path of the light,” said Harth.
Many athletes already take measures to reduce the impact of blue light through eye black or blue blocker sunglasses, but eating more foods rich in lutein and zeaxanthin can improve the eye’s natural ability to handle blue light exposure, said Harth.
When a person absorbs lutein and zeaxanthin, the compounds collect as yellow pigments in the retina and act as a filter to prevent blue light from entering the eye.
Previous work had been done testing the visual range ability of pilots in the 1980s, and Hammond and Renzi-Hammond have done more recent studies on how macular pigment density, or how much yellow pigment is built up in the retina, is linked to a number of measures of eye health and functional vision tests.
“In a long series of studies, we have shown that increasing amounts of lutein and zeaxanthin in the retina and brain decrease glare disability and discomfort and improve chromatic contrast and visual-motor reaction time, and supplementing these compounds facilitates executive functions like problem-solving and memory. All of these tasks are particularly important for athletes,” said corresponding author Billy R. Hammond, a professor of psychology in the Behavior and Brain Sciences Program at UGA’s Franklin College of Arts and Sciences.
This paper, Harth said, brings the research on these links between macular pigment and functional vision up to date and asks what the evidence suggests about optimizing athletic performance.
“We’re at a point where we can say we’ve seen visual range differences in pilots that match the differences found in modeling, and now, we’ve also seen it in laboratory tests, and a future goal would be to actually bring people outside and to measure their ability to see contrast over distance through real blue haze and in outdoor environments,” said Harth.
But before you start chowing down on kale in the hopes of improving your game, he cautions that everybody is different. That could mean the way our bodies absorb and use lutein and zeaxanthin varies, and it could take a while before you notice any improvements, if at all.
Still, the evidence of the overall health benefits of consuming more lutein and zeaxanthin are reason enough to add more color to your diet, say the authors.
“We have data from modeling and empirical studies showing that higher macular pigment in your retina will improve your ability to see over distance. The application for athletes is clear,” said Harth.
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