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Patients with inflammatory diseases involving peripheral organs or tissues commonly experience altered brain function giving rise to symptoms that adversely affect their quality of life (QOL) (D’Mello and Swain, 2014). How peripheral inflammation leads to remote changes in brain function remains unclear and, as a result, there are limited therapeutic options available clinically to address this issue. A number of general pathways have been described that link systemic inflammation to changes occurring in the brain, which in turn give rise to altered behavior (Dantzer et al., 2014).
These pathways traditionally have included signaling via neural pathways (mainly vagal nerve afferents) and immune signaling (mainly via circulating cytokines, which either enter the brain directly or activate cerebral endothelium; Capuron and Miller, 2011). Recently, we described a novel peripheral signaling pathway occurring in the setting of liver inflammation, which involves increased peripheral TNF-α production driving increased microglial activation, followed by monocyte recruitment into brain vasculature and brain parenchyma, which in turn drives the development of sickness behaviors (D’Mello et al., 2013).
The beneficial effect of probiotic consumption on behavior and brain function is now becoming increasingly appreciated in a variety of inflammatory diseases. Specifically, probiotic administration improves QOL in patients with irritable bowel syndrome (O’Mahony et al., 2005) and was associated with significant improvements in cognitive function and the restoration of impaired hippocampal long-term potentiation in a model of diabetes (Davari et al., 2013).
Potential peripheral pathways that link probiotic ingestion to changes in brain function have primarily focused on the role of vagal afferent nerve signaling and changes in cerebral levels of neuromodulators such as brain-derived neurotrophic factor (Bercik et al., 2010).
We now define an alternate signaling pathway established in the setting of liver inflammation, which links probiotic consumption to changes within the brain and alterations in behavior.
In patients with inflammatory disease and in animal models of systemic inflammation, probiotic ingestion has been previously shown by others to reduce circulating TNF-α levels (Loguercio et al., 2005; Dhiman et al., 2014; Sánchez et al., 2015; Vaghef-Mehrabany et al., 2014). In addition, probiotic treatment-induced reductions in circulating TNF-α levels were associated with improved neuropsychiatric outcomes, as seen in patients with chronic liver disease (Dhiman et al., 2014).
Our current findings in BDL mice parallel these clinical observations and are consistent with our previous studies demonstrating a critical role for elevated levels of TNF-α in the circulation of BDL mice driving sickness behavior development (D’Mello et al., 2009; D’Mello et al., 2013).
TNF-α-associated sickness behaviors in BDL mice are linked directly to cerebral microglial activation and recruitment of monocytes into the brain vasculature and brain parenchyma (D’Mello et al., 2009; D’Mello et al., 2013).
Observations of increased leukocyte recruitment to brain vasculature in a model of inflammatory bowel disease (D’Mello et al., 2009) was noted.
Our current findings are consistent with a role of probiotic ingestion in disrupting this signaling pathway in BDL mice.
TNF-α blockade using etanercept in probiotic-treated BDL mice did not further improve sickness behavior development, microglial activation, or cerebral monocyte infiltration in probiotic-treated BDL mice, consistent with the probiotic effects in BDL mice being TNF-α related. Interestingly, although probiotic treatment reduced circulating TNF-α levels in BDL mice to sham levels, sickness behavior development was not completely abrogated by probiotic treatment.
This finding suggests that alternative signaling pathways must also exist in BDL mice to cause sickness behaviors, possibly those driven by vagal afferent signaling to the brain (Capuron and Miller, 2011).
Changes in cross-talk among the intestinal epithelium, the intestinal immune system, and gut microbes has increasingly been recognized for its capacity to modulate systemic immunity (Belkaid and Naik, 2013). As a result, probiotics have been administered in an attempt to beneficially alter systemic immunity.
Consistent with this paradigm, administration of Bifidobacterium infantis to patients with irritable bowel syndrome was associated with an improvement in symptoms and a normalization of the IL-10 to IL-12 cytokine ratio in peripheral blood mononuclear cells (O’Mahony et al., 2005).
Probiotic treatment has been shown to reduce circulating levels of systemic proinflammatory biomarkers, including TNF-α levels, in patients with a range of systemic inflammatory conditions including psoriasis (Groeger et al., 2013), rheumatoid arthritis (Vaghef-Mehrabany et al., 2014), chronic fatigue syndrome, and liver disease (Loguercio et al., 2005; Dhiman et al., 2014); all findings replicated in our study.
Probiotic administration has been reported previously to induce increased intestinal production of the cytokine G-CSF (Martins et al., 2009). In our current study, consistent with this previous report, we found a striking increase in plasma G-CSF levels in probiotic-treated BDL mice compared with placebo-treated BDL and sham mice.
G-CSF can affect a wide variety of biological functions that are potentially relevant to our current experimental observations in probiotic-treated BDL mice. Specifically, G-CSF significantly attenuates monocyte/macrophage production of TNF-α (Nishiki et al., 2004).
G-CSF can mediate a reduction in cerebral inflammation (Nishiki et al., 2004). In BDL mice, monocyte/macrophage production of TNF-α is significantly enhanced compared with sham controls (Kerfoot et al., 2006; D’Mello et al., 2009). Therefore, increased plasma G-CSF levels in BDL mice treated with probiotic3 may contribute to the reduced circulating TNF-α levels observed in these mice and warrants future investigation.
Together, our data define a novel pathway whereby probiotic ingestion prevents peripheral inflammation-associated increases in circulating TNF-α levels, cerebral microglial activation, and recruitment of activated monocytes into the brain, ultimately attenuating BDL-associated sickness behavior development. Therefore, probiotic therapy may have a therapeutic role in regulating peripheral inflammation-associated brain dysfunction and behavioral alterations that often significantly affect patient quality of life (QOL).
Stress and Inflammation
During the last five years, it has been established that pro-inflammatory cytokines induce not only symptoms of sickness, but also true major depressive disorders in physically ill patients with no previous history of mental disorders. Some of the mechanisms that might be responsible for inflammation-mediated sickness and depression have now been elucidated. These findings suggest that the brain–cytokine system, which is in essence a diffuse system, is the unsuspected conductor of the ensemble of neuronal circuits and neurotrans-mitters that organize physiological and pathological behaviour. In this Review we discuss how the brain engenders sickness behaviour in response to peripheral infections. We then review the evidence that pro-inflammatory cytokines can also trigger the development of depression in vulnerable individuals, and the possible underlying mechanisms. Finally, we discuss how these actions of cytokines in the brain might have a role in at least part of the increased prevalence of depression in people with physical illness.
Probiotic Foods to Add to Your Diet
One of the best probiotic foods is live-cultured yogurt, especially handmade. Look for brands made from goat’s milk and infused with extra forms of probiotics like lactobacillus or acidophilus. Goat’s milk is a rich source of proteins, vitamins, and minerals while having better digestibility and lower allergenicity than cow’s milk. Goat milk yogurt is particularly high in probiotics like thermophillus, bifudus, and bulgaricus, and can be infused with extra forms of probiotics like lactobacillus or acidophilus.
Be sure to read the ingredients list, as not all yogurt is made equally. Many popular brands are filled with high fructose corn syrup, artificial sweeteners, and artificial flavors and are way too close to being a nutritional equivalent of sugary, fatty ice cream.
Similar to yogurt, this fermented dairy product is a unique combination of goat’s milk and fermented kefir grains. High in lactobacilli and bifidus bacteria, kefir is also rich in antioxidants. Look for a good, organic version at your local health food shop.
Similar to yogurt, this fermented dairy product is a unique combination of goat’s milk and fermented kefir grains. High in lactobacilli and bifidus bacteria, kefir is also rich in antioxidants. Look for a good, organic version at your local health food shop.
Made from fermented cabbage (and sometimes other vegetables), sauerkraut is not only extremely rich in healthy live cultures, but might also help with reducing allergy symptoms. Sauerkraut is also rich in vitamins A, B, C, and K.
4. Dark Chocolate
Chocolate itself doesn’t contain probiotics, but it was found to be a very effective carrier for probiotics. Chocolate helps them survive the extreme pHs of the digestive tract to make it to the colon. Because of this protective ability probiotics can be added to high-quality dark chocolate. This is only one of the many health benefits of chocolate.
This refers to super-food ocean-based plants such as spirulina, chlorella, and blue-green algae. While not a probiotic itself, microalgae can act as a prebiotic, which means that it feeds and nourishes the probiotics already in your gut. These prebiotic foods have been shown to increase beneficial bacteria and improve gastrointestinal health. They also offer the most amount of energetic return, per ounce, for the human system.
6. Miso Soup
Miso is one the mainstays of traditional Japanese medicine and is commonly used in macrobiotic cooking as a digestive regulator. Made from fermented rye, beans, rice or barley, adding a tablespoon of miso to some hot water makes an excellent, quick, probiotic-rich soup, full of lactobacilli and bifidus bacteria.
Beyond its important live cultures, miso is extremely nutrient-dense and believed to help neutralize the effects of environmental pollution, alkalinize the body and stop the effects of carcinogens in the system.
Believe it or not, the provincial pickle packs a punch of prime probiotics. In the U.S., the term “pickle” usually refers to pickled cucumbers specifically, but most vegetables can be pickled. All of them boast the same briny goodness and probiotic potential.
A great substitute for meat or tofu, tempeh is a fermented, probiotic-rich grain made from soybeans. A great source of vitamin B12, this vegetarian food can be sauteed, baked or eaten crumbled on salads. If prepared correctly, tempeh is also very low in salt, which makes it an ideal choice for those on a low-sodium diet.
An Asian form of pickled sauerkraut, kimchi is an extremely spicy and sour fermented cabbage, typically served alongside meals in Korea. Besides beneficial bacteria, Kimchi is also a great source of vitamin C, B vitamins, beta-carotene, calcium, iron, potassium, and dietary fiber. Kimchi is one of the best probiotic foods you can add to your diet, assuming you can handle the spice, of course.
10. Kombucha Tea
Kombucha is a form of fermented tea that contains a high amount of healthy gut bacteria. This probiotic drink has been used for centuries and is believed to help increase your energy, enhance your well-being and maybe even help you lose weight. However, kombucha tea may not be the best fit for everyone, especially those that have had problems with candida.
For excellent digestive health, fill your diet with as many prebiotic and probiotic foods as possible. I additionally recommend taking a good probiotic supplement. I recommend Floratrex™, a unique formula of 23 probiotic strains that helps support your digestive tract and boosts your immune system.
Summary: Researchers discover what they are calling social and asocial neurons in the prefrontal cortex.
The existence of new “social” neurons has just been demonstrated by scientists from the Institut de neurosciences des systèmes (Aix-Marseille University / INSERM), the Laboratoire de psychologie sociale et cognitive (Université Clermont Auvergne / CNRS), and the Institut de neurosciences de la Timone (Aix-Marseille University / CNRS). Their research on monkeys has shown that when these animals are made to perform a task, the presence or absence of a conspecific—that is, another monkey—determines which neurons are activated. Published in Social Cognitive and Affective Neuroscience, these findings broaden our knowledge of the social brain and help us better grasp the phenomenon of social facilitation.
Understanding how the brain functions within a social context is a major challenge facing neuroscientists. Through their unique multidisciplinary collaboration, a primate neurophysiologist and an experimental social psychologist have now discovered two new classes of neurons in the prefrontal cortex: social and asocial neurons.
Most areas of the brain are associated with specific tasks. Some are specialized in the processing of information related to life in society: they make up the so-called social brain. In connection with thesis research conducted by Marie Demolliens, CNRS researchers Driss Boussaoud and Pascal Huguet assigned monkeys the task of matching a picture shown on a touch screen with one of four different items displayed at the corners of the same screen. Executing such a task requires use of the prefrontal cortex but not the “social” areas of the brain. The researchers made daily recordings of neuronal electrical activity in this region of the brain while monkeys performed the task in the presence or in the absence of a conspecific.
Though the monitored neurons of the prefrontal cortex are primarily involved in execution of the visuomotor task, the study showed most of them also reacted strongly to either the presence or absence of another monkey. During the experiment, some of these neurons were only strongly activated in the presence of a conspecific. They have thus been dubbed social neurons. On the other hand, the activity levels of other, asocial neurons only spiked in the absence of a fellow monkey. Even more surprisingly, the greater the intensity of social neuron activity in the presence of a conspecific, the better the subject performed the task. Social neurons are hence at the root of social facilitation. Likewise, the greater the activity of asocial neurons in the absence of conspecifics, the better the subject performed the task—though not as well as in the presence of another, when social neurons are stimulated. The researchers also demonstrated that in the other, rare permutations—activation of social neurons in the absence of conspecifics, or of asocial neurons in their presence—the monkeys did not perform as well.
This work reveals the important connection between social context and neuronal activity, and the consequences on behavior: which neurons the brain uses depends on whether a conspecific is present, even if the task is the same. Thus, rather than being limited to the areas of the brain principally associated with social activity, social neurons might actually be dispersed throughout the brain and play a role in various tasks—whether or not the latter are social in nature. These findings cast new light on the nature of the social brain as well as certain behavioral disorders characteristic of autism and schizophrenia.
Source: Queen Muse – CNRS
Image Source: NeuroscienceNews.com image is credited to the researchers.
Original Research: Full open access research for “Social and asocial prefrontal cortex neurons: a new look at social facilitation and the social brain” by Marie Demolliens, Faiçal Isbaine, Sylvain Takerkart, Pascal Huguet, and Driss Boussaoud in Current Biology. Published online April 11 2017 doi:10.1093/scan/nsx053
Social and asocial prefrontal cortex neurons: a new look at social facilitation and the social brain
A fundamental aspect of behavior in many animal species is social facilitation, the positive effect of the mere presence of conspecifics on performance. To date, the neuronal counterpart of this ubiquitous phenomenon is unknown. We recorded the activity of single neurons from two prefrontal cortex regions, the dorsolateral part (PFdl) and the anterior cingulate cortex (ACC) in monkeys as they performed a visuomotor task, either in the presence of a conspecific (Presence condition) or alone. Monkeys performed better in the presence condition than alone (social facilitation), and analyses of outcome-related activity of 342 prefrontal neurons revealed that most of them (86%) were sensitive to the performance context. Two populations of neurons were discovered: “social neurons”, preferentially active under social presence, and “asocial neurons”, preferentially active under social isolation. The activity of these neurons correlated positively with performance only in their preferred context (social neurons under social presence; asocial neurons under social isolation), thereby providing a potential neuronal mechanism of social facilitation. More generally, the fact that identical tasks recruited either social or asocial neurons depending on the presence or absence of a conspecific also brings a new look at the social brain hypothesis.
“Social and asocial prefrontal cortex neurons: a new look at social facilitation and the social brain” by Marie Demolliens, Faiçal Isbaine, Sylvain Takerkart, Pascal Huguet, and Driss Boussaoud in Current Biology. Published online April 11 2017 doi:10.1093/scan/nsx053
Summary: Findings may explain how neurodegenerative diseases spread throughout the brain and disrupt normal functions. Additionally, treatment for one disease could possibly work for the other two also.
Source: Karolinska Institute.
What happens in the brain when we see other people experiencing a trauma or being subjected to pain? Well, the same regions that are involved when we feel pain ourselves are also activated when we observe other people who appear to be going through some painful experience. This is shown in a study from Karolinska Institutet in Sweden published in Nature Communications. But we are sensitive to different degrees to learning fear from other people and one explanation would appear to be found in the endogenous opioid system.
Seeing others express pain or anxiety can give us important information about things around us that are dangerous and should be avoided. Sometimes, however, we can develop fear of situations that, rationally speaking, are not dangerous. The opioid system is supposed to alleviate pain and fear but it does not work as effectively in all of us, which might be one of the reasons why some people develop anxiety syndrome merely by seeing others experience a trauma.
“Some people are over-sensitive to this form of social learning. Our study shows that the endogenous opioid system affects how sensitive we are and may explain why some people develop post-traumatic stress disorder (PTSD) merely by observing others who are experiencing traumatic events. After terror attacks, sensitive people might be afraid even if they themselves were not present,” says main author Jan Haaker, associated researcher at Karolinska Institutet’s Department of Clinical Neuroscience.
In a double-blind study, the researchers altered the brain’s internal chemistry in 22 healthy subjects by using a pharmaceutical substance to block the opioid system. 21 subjects were given an inactive placebo. The subjects then watched a video where other people were subjected to electric shocks.
The brain normally updates its knowledge of danger based on whether we are surprised, but when the opioid system was blocked, the people continued to react as if they were surprised even though they knew the electric shock would come. And the response was amplified even when they continued to watch other people being subjected to shocks. The response increased in regions of the brain such as the amygdala, the periaqueductal gray and the thalamus, which seems to indicate that the same functions as in self-perceived pain were involved. Communication also increased between these and other regions of the brain that were previously linked to the ability to understand other individuals’ experiences and thoughts.
“When the people participating in the experiment were themselves subjected to threatening stimuli that they had previously associated with other people’s pain, they perspired more and displayed more fear than those who had been given a placebo. This enhanced learning was even visible three days after the social learning episode,” says research team leader Andreas Olsson, senior lecturer at Karolinska Institutet’s Department of Clinical Neuroscience.
The study contributes to greater understanding of the psychology behind fear. The researchers hope that the new findings will eventually mean that people with anxiety conditions will be able to be given better, more individual-adapted clinical help.
Funding: The research was financed by the European Research Council (ERC), the Knut and Alice Wallenberg Foundation and the German Research Foundation (DFG).
Source: Jan Haaker – Karolinska Institute
Image Source: NeuroscienceNews.com image is credited to Loyola University Chicago.
Original Research: Full open access research for “Endogenous opioids regulate social threat learning in humans” by Jan Haaker, Jonathan Yi, Predrag Petrovic & Andreas Olsson in Nature Communications. Published online May 25 2017 doi:10.1038/ncomms15495
Endogenous opioids regulate social threat learning in humans
Many fearful expectations are shaped by observation of aversive outcomes to others. Yet, the neurochemistry regulating social learning is unknown. Previous research has shown that during direct (Pavlovian) threat learning, information about personally experienced outcomes is regulated by the release of endogenous opioids, and activity within the amygdala and periaqueductal gray (PAG). Here we report that blockade of this opioidergic circuit enhances social threat learning through observation in humans involving activity within the amygdala, midline thalamus and the PAG. In particular, anticipatory responses to learned threat cues (CS) were associated with temporal dynamics in the PAG, coding the observed aversive outcomes to other (observational US). In addition, pharmacological challenge of the opioid receptor function is classified by distinct brain activity patterns during the expression of conditioned threats. Our results reveal an opioidergic circuit that codes the observed aversive outcomes to others into threat responses and long-term memory in the observer.
“Endogenous opioids regulate social threat learning in humans” by Jan Haaker, Jonathan Yi, Predrag Petrovic & Andreas Olsson in Nature Communications. Published online May 25 2017 doi:10.1038/ncomms15495
Summary: Researchers have identified brain differences in people with a genetic risk factor for autism and schizophrenia.
Deletions or duplications of DNA along 22nd chromosome hint at biological underpinnings of these disorders.
A UCLA study characterizes, for the first time, brain differences between people with a specific genetic risk for schizophrenia and those at risk for autism, and the findings could help explain the biological underpinnings of these neuropsychiatric disorders.The research, published May 23 in the Journal of Neuroscience, sheds light on how an excess, or absence, of genetic material on a particular chromosome affects neural development.
“Notably, the opposing anatomical patterns we observed were most prominent in brain regions important for social functioning,” said Carrie Bearden, lead author of the study and a professor of professor of psychiatry and biobehavioral sciences, and of psychology, at UCLA. “These findings provide clues into differences in brain development that may predispose to schizophrenia or autism.”
Bearden’s earlier research had focused on children with abnormalities caused by missing sections of genetic material on chromosome 22, in a location known as 22q11.2. The disorder, called 22q11.2-deletion syndrome, can cause developmental delays, heart defects and distinct facial features. It also confers the highest-known genetic risk for schizophrenia.
Then she learned that people with 22q duplication — abnormal repetition, or duplication, of genetic material in chromosome 22 — had learning delays and sometimes autism, but a lower risk for schizophrenia than that found in the general population. In other words, duplication of genetic material in this region seemed to provide some protection against schizophrenia.
For the current study, Bearden, who is part of the UCLA Semel Institute for Neuroscience and Human Behavior, conducted MRI scans of 143 study participants: 66 with 22q deletions, 21 with 22q duplications, and 56 without the genetic mutation.
Those in the group with 22q deletion, which carries the risk for schizophrenia, had thicker gray matter, but less brain surface area — a measure which relates to how folded the brain is — compared to those in the duplication group. The people in the 22q duplication group, who at risk for autism, had the opposite pattern, with thinner gray matter and larger brain surface area.
“The next question is how does brain anatomy — and brain function — relate to psychiatric outcomes? These findings provide a snapshot,” Bearden said. “We are now conducting follow-up studies to track predictors of outcome over time. Those are the puzzle pieces that are next on our list to disentangle.”
These structures are not sole determinants of schizophrenia or autism, Bearden said, but rather, more dots in the connect-the-dots puzzle of understanding these disorders. Observing this group of people over time could provide insights on how other risk factors or life events, such as puberty, affect the mind.
Bearden says she and her team are collaborating with other scientists to investigate brain structural differences in animal models, to find out what causes them at the cellular level.
The study’s first author is Amy Lin, a doctoral student in the UCLA neuroscience program. Other authors are Ariana Vajdi, Daqiang Sun, Rachel Jonas, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Deepika Dokuru, Gerhard Helleman, all of UCLA; Maria Jalbrzikowski of the University of Pittsburgh Medical Center; Paul Thompson and Boris Gutman of USC; and Christopher Ching of UCLA and USC.
Funding: The research was funded by the Simons Foundation, the National Institute of Mental Health (RO1 MH085953), and a Neurobehavioral Genetics Predoctoral Training Grant (5T32MH073526).
Source: Leigh Hopper – UCLA
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry” by Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K. Jonas, Maria Jalbrzikowski, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Boris Gutman, Deepika Dokoru, Gerhard Helleman, Paul M. Thompson and Carrie E. Bearden in Journal of Neuroscience. Published online May 23 2017 doi:10.1523/JNEUROSCI.3759-16.2017
Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry
Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control< duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in sub-regions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development.
Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly, reciprocal genomic imbalances at this locus confer some of the highest known genetic risks for developmental neuropsychiatric disorders. Here we provide the first evidence that brain morphology differs meaningfully as a function of reciprocal genomic variation at the 22q11.2 locus. Cortical thickness and surface area were affected in opposite directions with more widespread effects of gene dosage on cortical surface area.
“Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry” by Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K. Jonas, Maria Jalbrzikowski, Leila Kushan-Wells, Laura Pacheco Hansen, Emma Krikorian, Boris Gutman, Deepika Dokoru, Gerhard Helleman, Paul M. Thompson and Carrie E. Bearden in Journal of Neuroscience. Published online May 23 2017 doi:10.1523/JNEUROSCI.3759-16.2017
Summary: Researchers report brain network organization changes can influence executive function in young adults.
Source: University of Pennsylvania.
Network organization changes influence improvements in executive function among adolescents and young adults.
As children age into adolescence and on into young adulthood, they show dramatic improvements in their ability to control impulses, stay organized, and make decisions. Those executive functions of the brain are key factors in determining outcomes including their educational success, and whether they will use recreational drugs, or develop psychiatric illness. In a new study, published this week in Current Biology, a team of University of Pennsylvania researchers report newly mapped changes in the network organization of the brain that underlie those improvements in executive function. The findings could provide clues about risks for certain mental illnesses.
The study, led by Ted Satterthwaite, MD, an assistant professor of Psychiatry, Danielle Bassett, PhD, an associate professor of Bioengineering, and Graham Baum, a neuroscience doctoral student supervised by Satterthwaite and Bassett, reveals that in adolescence the brain networks becomes increasingly divided into distinct parts, called modules. Modules are parts of a network that are tightly connected to each other, and less connected to other parts of the network. Modules are thought to support specialized brain functions like movement, sensation, vision, and more complicated tasks like executive function. The new evidence shows that the degree to which executive function develops during this period in part depends on the degree to which these modules are present.
“We were surprised to find that the development of structural brain networks involved both more distinct modules but also more global integration across the brain,” Satterthwaite said.
The findings suggest that these modular sub-networks are critical for the development of complex cognition and behavior. They could also lead to the identification of biomarkers of abnormal brain development that could predict a person’s risk for psychosis and major mood disorders.
Satterthwaite and his team set out to define the normal development of structural network modules and its relationship to executive functioning using a large sample of 882 youth between the ages of 8 and 22 who completed diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, a National Institute of Mental Health (NIMH)-funded study of brain development led by Raquel Gur, MD, PhD, a professor of Psychiatry, Neurology and Radiology. As expected, executive function improved markedly in study participants with age. An analysis of specialized brain MRI scans allowed the team to estimate structural brain networks for each participant. Analyses of these networks revealed that modules became more defined with age, but also that the network as a whole became more integrated.
“The development of network modules did not result in the brain network becoming fragmented,” Baum explained. “In fact, the brain’s predicted ability to send signals efficiently across the whole network actually increased. These results suggest that as kids grow up, their brains become both more modular but also more globally integrated. This may allow the brain to have specialized units that can work together to support advanced cognitive abilities.”
Satterthwaite, Bassett and Baum suggest that modular brain organization may be critical for supporting specific types of processing. At the same time, the increase in integration across the network may allow those specialized parts to work together in a coordinated fashion. The researchers found that both the presence of specialized network modules and the ability to send information across the network was significantly related to a person’s performance on tests of executive function.
The research team is now combining structural and functional imaging techniques, to examine how structural brain networks constrain and shape functional brain networks and activation patterns. They will also investigate whether information about brain networks can predict the emergence of psychiatric disorders in children years later..
Other Penn Medicine investigators involved in the study include Ruben C. Gur, PhD, Raquel Gur, MD, PhD, Rastko Ciric, David R. Roalf, PhD, Richard F. Betzel, PhD, Tyler M. Moore, PhD, Russell T. Shinohara, PhD, Ari E. Kahn, Simon N. Vandekar, Petra E. Rupert, Megan Quarmley, BS, Phillip A. Cook, PhD, Mark A. Elliott, PhD, and Kosha Ruparel, MSE.
Source: Queen Muse – University of Pennsylvania
Image Source: NeuroscienceNews.com image is credited to Penn Medicine.
Original Research: Full open access research for “Modular Segregation of Structural Brain Networks Supports the Development of Executive Function in Youth” by Graham L. Baum, Rastko Ciric, David R. Roalf, Richard F. Betzel, Tyler M. Moore, Russell T. Shinohara, Ari E. Kahn, Simon N. Vandekar, Petra E. Rupert, Megan Quarmley, Philip A. Cook, Mark A. Elliott, Kosha Ruparel, Raquel E. Gur, Ruben C. Gur, Danielle S. Bassett, Theodore D. Satterthwaite in Current Biology. Published online May 25 2017 doi:10.1016/j.cub.2017.04.051
Modular Segregation of Structural Brain Networks Supports the Development of Executive Function in Youth
•Structural brain modules become more segregated during youth
•Targeted strengthening of hub edges simultaneously promotes network efficiency
•Enhanced modular segregation mediates improvements in executive function in youth
The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence. However, it remains unknown whether the underlying white matter architecture is similarly refined during development, potentially allowing for improvements in executive function. In a sample of 882 participants (ages 8–22) who underwent diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that structural network modules become more segregated with age, with weaker connections between modules and stronger connections within modules. Evolving modular topology facilitates global network efficiency and is driven by age-related strengthening of hub edges present both within and between modules. Critically, both modular segregation and network efficiency are associated with enhanced executive performance and mediate the improvement of executive functioning with age. Together, results delineate a process of structural network maturation that supports executive function in youth.
“Modular Segregation of Structural Brain Networks Supports the Development of Executive Function in Youth” by Graham L. Baum, Rastko Ciric, David R. Roalf, Richard F. Betzel, Tyler M. Moore, Russell T. Shinohara, Ari E. Kahn, Simon N. Vandekar, Petra E. Rupert, Megan Quarmley, Philip A. Cook, Mark A. Elliott, Kosha Ruparel, Raquel E. Gur, Ruben C. Gur, Danielle S. Bassett, Theodore D. Satterthwaite in Current Biology. Published online May 25 2017 doi:10.1016/j.cub.2017.04.051