Research identifies changes in neural circuits underlying self-control during adolescence

Self control concept (stock image).

The human brain is organized into circuits that develop from childhood through adulthood to support executive function -- critical behaviors like self-control, decision making, and complex thought. These circuits are anchored by white matter pathways which coordinate the brain activity necessary for cognition. However, little research exists to explain how white matter matures to support activity that allows for improved executive function during adolescence -- a period of rapid brain development.

Researchers from the Lifespan Brain Institute of the Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia applied tools from network science to identify how anatomical connections in the brain develop to support neural activity underlying these key areas. The findings were published in the Proceedings of the National Academy of Sciences.

"By charting brain development across childhood and adolescence, we can better understand how the brain supports executive function and self-control in both healthy kids and those with different mental health experiences," said the study's senior author Theodore Satterthwaite, MD, an assistant professor of Psychiatry at Penn. "Since abnormalities in developing brain connectivity and deficits in executive function are often linked to the emergence of mental illness during youth, our findings may help identify biomarkers of brain development that predict cognitive and clinical outcomes later in life."

In this study, the researchers mapped structure-function coupling -- the degree to which a brain region's pattern of anatomical connections supports synchronized neural activity. This could be thought of like a highway, where the anatomical connections are the road and the functional connections are the traffic flowing along those roads. Researchers mapped and analyzed multi-modal neuroimaging data from 727 participants ages 8 to 23 years, and three major findings emerged.

First, the team found that regional variability in structure-function coupling was inversely related to the complexity of the function a given brain area is responsible for. Higher structure-function coupling was found in parts of the brain that are specialized for processing simple sensory information, like the visual system. In contrast, there was lower structure-function coupling in complex parts of the brain that are responsible for executive function and self-control, which require more abstract and flexible processing.

Results showed that structure-function coupling also aligned with known patterns of brain expansion over the course of primate evolution. Previous work comparing human, ape, and monkey brains has showed that sensory areas like the visual system are highly conserved across primate species and have not expanded much during recent evolution. In contrast, association areas of the brain, such as the prefrontal cortex, have expanded dramatically over the course of primate evolution. This expansion may have allowed for the emergence of uniquely complex human cognitive abilities. The team found that the brain areas which expanded rapidly during evolution had lower structure-function coupling, while simple sensory areas that have been conserved in recent evolution had higher structure-function coupling.

Researchers also found that structure-function coupling increased throughout childhood and adolescence in complex frontal brain regions. These are the same regions that tend to have lower baseline structure-function coupling, are expanded compared to monkeys, and are responsible for self-control. The prolonged development of structure-function coupling in these regions may allow for improved executive function and self-control that develops into adulthood. Indeed, the team found that higher structure-function coupling in the lateral prefrontal cortex -- a complex brain area which plays important roles in self-control -- was associated with better executive function.

"These results suggest that executive functions like impulse control -- which can be particularly challenging for children and adolescents -- rely in part on the prolonged development of structure-function coupling in complex brain areas like the prefrontal cortex," explained lead author Graham Baum, PhD, a postdoctoral fellow at Harvard University, who was a Penn neuroscience PhD student during the time of the research. "This has important implications for understanding how brain circuits become specialized during development to support flexible and appropriate goal-oriented behavior."

Additional Penn co-authors include Zaixu Cui, David R. Roalf, Bart Larsen, Matthew Cieslak, Philip A. Cook, Cedric H. Xia, Tyler M. Moore, Kosha Ruparel. Desmond Oathes, Russell T. Shinohara, Raquel E. Gur, Ruben C. Gur, and Danielle S. Bassett.

This work was supported by the National Institute of Mental Health (F31MH115709, R01MH113550, MH089983, MH089924, R01MH107703, R01MH112847, R01MH107235, P50MH096891, K01MH102609, R01NS085211, RF1MH116920). Additional support was provided by the Lifespan Brain Institute.

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Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

---

Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Research identifies changes in neural circuits underlying self-control during adolescence

Self control concept (stock image).

Credit: © tashatuvango / Adobe Stock

The human brain is organized into circuits that develop from childhood through adulthood to support executive function -- critical behaviors like self-control, decision making, and complex thought. These circuits are anchored by white matter pathways which coordinate the brain activity necessary for cognition. However, little research exists to explain how white matter matures to support activity that allows for improved executive function during adolescence -- a period of rapid brain development.

Researchers from the Lifespan Brain Institute of the Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia applied tools from network science to identify how anatomical connections in the brain develop to support neural activity underlying these key areas. The findings were published in the Proceedings of the National Academy of Sciences.

"By charting brain development across childhood and adolescence, we can better understand how the brain supports executive function and self-control in both healthy kids and those with different mental health experiences," said the study's senior author Theodore Satterthwaite, MD, an assistant professor of Psychiatry at Penn. "Since abnormalities in developing brain connectivity and deficits in executive function are often linked to the emergence of mental illness during youth, our findings may help identify biomarkers of brain development that predict cognitive and clinical outcomes later in life."

In this study, the researchers mapped structure-function coupling -- the degree to which a brain region's pattern of anatomical connections supports synchronized neural activity. This could be thought of like a highway, where the anatomical connections are the road and the functional connections are the traffic flowing along those roads. Researchers mapped and analyzed multi-modal neuroimaging data from 727 participants ages 8 to 23 years, and three major findings emerged.

First, the team found that regional variability in structure-function coupling was inversely related to the complexity of the function a given brain area is responsible for. Higher structure-function coupling was found in parts of the brain that are specialized for processing simple sensory information, like the visual system. In contrast, there was lower structure-function coupling in complex parts of the brain that are responsible for executive function and self-control, which require more abstract and flexible processing.

Results showed that structure-function coupling also aligned with known patterns of brain expansion over the course of primate evolution. Previous work comparing human, ape, and monkey brains has showed that sensory areas like the visual system are highly conserved across primate species and have not expanded much during recent evolution. In contrast, association areas of the brain, such as the prefrontal cortex, have expanded dramatically over the course of primate evolution. This expansion may have allowed for the emergence of uniquely complex human cognitive abilities. The team found that the brain areas which expanded rapidly during evolution had lower structure-function coupling, while simple sensory areas that have been conserved in recent evolution had higher structure-function coupling.

Researchers also found that structure-function coupling increased throughout childhood and adolescence in complex frontal brain regions. These are the same regions that tend to have lower baseline structure-function coupling, are expanded compared to monkeys, and are responsible for self-control. The prolonged development of structure-function coupling in these regions may allow for improved executive function and self-control that develops into adulthood. Indeed, the team found that higher structure-function coupling in the lateral prefrontal cortex -- a complex brain area which plays important roles in self-control -- was associated with better executive function.

"These results suggest that executive functions like impulse control -- which can be particularly challenging for children and adolescents -- rely in part on the prolonged development of structure-function coupling in complex brain areas like the prefrontal cortex," explained lead author Graham Baum, PhD, a postdoctoral fellow at Harvard University, who was a Penn neuroscience PhD student during the time of the research. "This has important implications for understanding how brain circuits become specialized during development to support flexible and appropriate goal-oriented behavior."

Additional Penn co-authors include Zaixu Cui, David R. Roalf, Bart Larsen, Matthew Cieslak, Philip A. Cook, Cedric H. Xia, Tyler M. Moore, Kosha Ruparel. Desmond Oathes, Russell T. Shinohara, Raquel E. Gur, Ruben C. Gur, and Danielle S. Bassett.

This work was supported by the National Institute of Mental Health (F31MH115709, R01MH113550, MH089983, MH089924, R01MH107703, R01MH112847, R01MH107235, P50MH096891, K01MH102609, R01NS085211, RF1MH116920). Additional support was provided by the Lifespan Brain Institute.

---

Story Source:

Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

---

Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

---

Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

---

Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.