Insights into Neurobiology of Restless Legs Syndrome

MedicalResearch.com Interview with:

Rachel Marie E. Salas, MD, MEHP, FAAN Associate Professor, Neurology and Nursing at Johns Hopkins Medicine Director, Interprofessional Education and Interprofessional Collaborative Practice Director, Neurology Clerkship Director, PreDoc Program Meyer/Neuro Sleep Baltimore, MD

Dr Salas

Rachel Marie E. Salas, MD, MEHP, FAAN
Associate Professor, Neurology and Nursing at Johns Hopkins Medicine
Director, Interprofessional Education and Interprofessional Collaborative Practice
Director, Neurology Clerkship
Director, PreDoc Program Meyer/Neuro Sleep
Baltimore, MD

MedicalResearch.com: What is the background for this study? Can you briefly describe what is meant by RLS  and who suffers from it?

Response: Restless Legs Syndrome (RLS) is a common neurological disorder characterized by an irritating, overwhelming urge to move (akathisia) the legs while at rest or sleep (conditions of diminished arousal), which almost immediately abates with mental or physical activity (conditions of maintained arousal).

One of the most clinically-profound and scientifically relevant consequences of this disease process is an increased arousal state producing significant wake during sleep times and a relative sustainable degree of daytime alertness despite the degree of diseased-imposed sleep loss. The focus of most previous RLS research has been on the (limb) akathisia with associated periodic movements and reduction of these with dopaminergic treatment. Little research has been done to understand the broader biological dimensions​ of RLS. Patients with RLS have altered sleep-wake homeostasis with increased arousal and wakefulness (hyperarousal) not only driving the signature clinical symptoms (“the urge to move” and sleep loss) but also supporting arousal over sleep drive at night and in the day. We hypothesize that there is a basic glutamate-hyperarousal process producing both disrupted sleep (increased wake time) and cortical excitability (as demonstrated by transcranial magnetic stimulation (TMS)).​  Continue reading

Brain Circuits in Compulsive Alcohol Drinkers Identified

MedicalResearch.com Interview with:

Erica Grodin, Ph.D. Postdoctoral Fellow Dept. of Psychology and Psychiatry  University of California

Dr. Grodin

Erica Grodin, Ph.D.
Postdoctoral Fellow
Dept. of Psychology and Psychiatry
University of California 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The hallmark of addictive disorders, including alcohol use disorder, is drug use that continues despite negative consequences. This pattern of use is referred to as “compulsive” and is one of the major barriers to treating addiction. We don’t yet fully understand what brain regions are responsible for compulsive alcohol use.

Our study used a neuroimaging method called functional magnetic resonance imaging which allows us to see which areas of the brain are more active when an individual is performing a task. To investigate what brain regions are involved in compulsive alcohol seeking, we designed a task during which study participants could try to earn alcohol and food points at the risk of receiving a negative consequence, an electric shock. Study participants were light drinkers (men who drank <15 drinks/week and women who drank <10 drinks/week) and heavy drinkers (men who drank ≥20 drinks/week and women who drank ≥15 drinks/week).

We found that heavy drinking individuals were more likely to try to earn alcohol points that were paired with a potential negative consequence than light drinkers were. This behavior of compulsive alcohol seeking was associated with increased brain activation in the medial prefrontal cortex, anterior insula, and ventral and dorsal striatum.  Continue reading

Infants Are Lips Experts With Prominent Neural Map of Lips

MedicalResearch.com Interview with:

Andrew N. Meltzoff Ph.D. Job and Gertrud Tamaki Endowed Chair Co-Director, Institute for Learning & Brain Sciences (I-LABS) Professor of Psychology Elected member of the American Academy of Arts & Sciences. University of Washington, Box 357920 Seattle, WA 98195

Dr. Meltzoff

Andrew N. Meltzoff Ph.D.
Job and Gertrud Tamaki Endowed Chair
Co-Director, Institute for Learning & Brain Sciences (I-LABS)
Professor of Psychology
Elected member of the American Academy of Arts & Sciences.
University of Washington, Box 357920
Seattle, WA 98195

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: We are applying safe, noninvasive neuroscience techniques to examine the development of young children. We are especially interested in social-emotional learning and cognitive development. The way the body is represented in the brain is well-studied topic in cognitive neuroscience using adults, for example, the classical studies by W. Penfield on the ‘sensorimotor homunculus’ in the adult brain. The development of neural body map in human infants is, however, deeply understudied.

We think that the way the body is represented in the brain will provide important information about infant learning prior to language. For example, one of the chief avenues of learning in human infants is through observation and imitation. Infants watch what adults do and imitate those behaviors, rapidly learning about people, things, and causal relations. The mechanisms of imitation themselves are interesting. In order to imitate, infants need to know what part of their body to move and how to move it. We wanted to explore the representations of the human body in the infant brain prior to language. Continue reading

Major Brain Networks With Altered Brain Function In Individuals with Addiction Identified

MedicalResearch.com Interview with:
Professor, Rita Z. Goldstein, PhD
Department of Psychiatry (primary)
and Department of Neuroscience, Friedman Brain Institute (secondary)
Chief, Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program

Anna Zilverstand PhD
Assistant Professor, Psychiatry

Icahn School of Medicine at Mount Sinai
The Leon and Norma Hess Center for Science and Medicine
New York, NY 10029 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In comparison to previous reviews that often focused on investigating select brain circuits, such as the reward network, our review is the first to systematically discuss all brain networks implicated in human drug addiction. Based on more than 100 neuroimaging studies published since 2010, we found that six major brain networks showed altered brain function in individuals with addiction. These brain circuits are involved in a person’s ability to select their actions (executive network), in directing someone’s attention (salience network), in adaptive learning of new behaviors (memory network), in the automatization of behaviors (habit network), in self-reflection (self-directed network) and the valuation of different options (reward network).

When individuals with addiction are confronted with pictures of drug taking, all of these networks become very highly engaged; however, when the same individuals are confronted with scenes depicting other people, their brains show a reduced reaction as compared to healthy individuals, indicating less involvement. Similarly, the brain of an addicted individual is less engaged when making decisions (that are not relevant to their drug taking) or when trying to inhibit impulsive actions. We further found that some impairments of brain functions, such as alterations underlying the difficulty to inhibit impulsive actions, seem to precede drug addiction, as we observe similar impairments in adolescents that later go on to abuse drugs. However, particularly the impairments in the executive network (involved in the ability to inhibit impulsive actions), the valuation network (which computes the value of an option) and the salience network (that directs attention towards events) seem to be getting worse with more severe drug use and also predict if someone is likely to relapse or not.

The good news is that we also found that it is possible to (partially) recover and normalize brain function in these networks through treatment. Importantly, the widespread alterations of brain function were independent of what drug an individual was addicted to (marijuana, alcohol, cigarettes, cocaine, methamphetamine, heroin, amongst others). Continue reading

Genes Linked To Large Brains in Humans Identified

MedicalResearch.com Interview with:
“The human Brain” by Kristian Mollenborg is licensed under CC BY 2.0David Haussler PhD

Investigator, Howard Hughes Medical Institute
Distinguished Professor, Biomolecular Engineering
Scientific Director, UC Santa Cruz Genomics Institute
Scientific Co-Director, California Institute for Quantitative Biosciences  and

Sofie Salama, PhD
Research Scientist in BIomolecular Engineering
Howard Hughes Medical Institute Senior Scientist

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Haussler:  Researchers specializing in this area are interested understanding which evolutionary changes in our genome underlie human-specific brain features including our large (3X greater than chimpanzee) brain.

It has been my personal dream to peer into human evolution at the level of individual genes and gene functions.  Continue reading

Could Oxytocin Be a Social Equalizer?

MedicalResearch.com Interview with:
“Monkeys” by Dmitry Baranovskiy is licensed under CC BY 2.0Yaoguang Jiang PhD
Postdoctoral Researcher
PLATT Lab
University of Pennsylvania 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Oxytocin (OT) and arginine vasopressin (AVP) are important neuropeptides known to influence social behaviors in a wide array of mammals. In humans, OT is widely referred to as the ‘prosocial’ hormone and is thought to promote social functions in neurotypical individuals as well as those diagnosed with autism spectrum disorder (ASD). Currently, dozens of ongoing clinical trials in the US are trying to evaluate the therapeutic potential of these neuropeptides in remedying social deficits associated with disorders such as ASD. Yet there are significant gaps in our knowledge especially regarding the neurobiological basis of OT and AVP function. Most importantly, we are unclear which brain areas and pathways these neuropeptides act on to influence social behavior. Additionally, due to strong similarity in molecular structure, OT can bind to AVP receptors with high affinity and vice versa, making it difficult to rule out the possibility that, for example, the behavioral effect of exogenous oxytocin is mediated through the AVP system. Both of these questions have been thoroughly investigated in rodents, but unfortunately the same thing cannot be said for humans.

Our study aims to bridge the gap between rodent and human literature on neuropeptide function by studying rhesus macaque monkeys. These monkeys resemble human beings not only in their social behaviors, but also in the neural network that is supporting those behaviors. In this study we show that treating one male macaque monkey intranasally with aerosolized OT relaxes his spontaneous social interactions with another monkey.

Oxytocin reduces differences in social behavior between dominant and subordinate monkeys, thereby flattening the status hierarchy.Oxytocin also increases behavioral synchrony within a pair, perhaps through increased attention and improved communication. Intranasal delivery of aerosolized AVP reproduces the effects of OT with greater efficacy. Remarkably, all behavioral effects are replicated when either OT or AVP is injected focally into the anterior cingulate gyrus (ACCg), a brain area linked to empathy, vicarious reward, and other-regarding behavior. ACCg lacks post-synaptic OT receptors but is rich in post-synaptic AVP receptors, suggesting exogenous OT may shape social behavior, in part, via nonspecific binding, particularly when available at supra-physiological concentrations.  Continue reading

How does SURPRISE! Make You Stop What You Are Doing?

MedicalResearch.com Interview with:

Jan R. Wessel, Ph.D. Asst. Professor Department of Psychological and Brain Sciences Department of Neurology Iowa Neuroscience Institute University of Iowa

Dr. Wessel

Jan R. Wessel, Ph.D.
Asst. Professor
Department of Psychological and Brain Sciences
Department of Neurology
Iowa Neuroscience Institute
University of Iowa 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: We found that the occurence of unexpected events, such as sudden, surprising sounds lead to an automatic engagement of a well-known brain network for action-stopping, thereby leading to a suppression of ongoing motor activity. Specifically, we found that when participants had to stop an action, their ability to do so was significantly improved when the cue to stop was accompanied by a sudden, unexpected sound. This improvement was accompanied by an amplification of the brain activity that is related to action-stopping, and was also accompanied by an increase of suppression of excitability of the motor cortex.  Continue reading

Alcohol Doesn’t Cause Aggression By Simple Disinhibition

MedicalResearch.com Interview with:
“Alcohol” by zeevveez is licensed under CC BY 2.0Thomas Denson PhD

University of New South Wales
Australia 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Decades of research have shown that alcohol is a powerful psychotropic contributor to aggressive behaviour. Researchers have long suspected that alcohol increases aggression because it dampens activation in the prefrontal cortex, which leads to reduced inhibition, narrows attentional processing, and exaggerates hostile thinking. However, direct evidence has been lacking. We compared brain activity in intoxicated versus sober participants when they were given the opportunity to behave aggressively in the scanner against other men who provoked them.

We gave 50 healthy young men alcohol or a placebo. Participants who consumed alcohol breathalysed at .05. They did show decreased activation in the prefrontal cortex as expected. This was the first evidence to show that when intoxicated participants behave aggressively, they show reduced prefrontal activity. Interestingly, we found a positively correlation between prefrontal cortex activity and aggression, but only among intoxicated men. We think this reflects the fact that the participants in the alcohol condition were likely engaging in more hostile thinking about the provoking men.  Continue reading

Neurobiology of Jealousy Mapped In Monkey Brains

MedicalResearch.com Interview with:

Monogamous  Titi monkeys

Monogamous Titi monkeys

Karen L. Bales PhD
Professor of Psychology
University of California
Davis, CA 95616

MedicalResearch.com: What is the background for this study?

Response:  Titi monkeys are a socially monogamous species in which adults form pair bonds.  In my laboratory we are studying the neurobiology of pair bonding, and understanding jealousy is important because it’s one mechanism by which the pair bond is maintained.  In this study, male titi monkeys viewed their pair mate next to a stranger male, and we examined the neural, behavioral, and hormonal consequences.  Continue reading

Schizophrenia: Impaired White Matter Linked To Deficits in Cognitive Processing Speed

MedicalResearch.com Interview with:

Peter Kochunov PhD Professor Maryland Psychiatric Research Center

Dr. Kochunov

Peter Kochunov PhD
Professor
Maryland Psychiatric Research Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Schizophrenia is a debilitating disorder that strikes young people at the point of entering adulthood. In the past, we and others demonstrated that patients with schizophrenia are characterized by deficits in the white matter of the brain. White matter is the part of the brain that serves the backbone of cerebral networks transmitting information and interconnecting brain regions.

In this report, we link the impaired white matter of the brain in schizophrenia patients with the disorder-related deficits in the processing speed. We also showed that mental processing speed is a fundamental cognitive construct that partially supports other functions like working memory in patients, where processing speed acting as the intermediate between white matter deficits and reduced working memory. This interesting relationship between processing speed, working memory, and white matter is most obvious in white matter regions most vulnerable to schizophrenia. That was the main finding of the study.

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Religious and Non Religious Use Different Cognitive Pathways To Form Opinions

MedicalResearch.com Interview with:

Jared Friedman Doctoral Student, Organizational Behavior Research Assistant II, Brain Mind and Consciousness Lab Case Western Reserve University

Jared Friedman

Jared Friedman
Doctoral Student, Organizational Behavior
Research Assistant II, Brain Mind and Consciousness Lab
Case Western Reserve University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: These studies were motivated by our prior work in neuroscience and psychology.  Neuroscience research from our lab has shown that brain areas associated with empathy seem to share a ‘see-saw’ relationship with brain areas associated with analytic reasoning.  As activity in one set of brain areas goes up, activity in the other set of brain areas tends to go down.  This suggests there is a sort of neural antagonism between warm, empathic sorts of thinking on the one hand, and cold, analytic sorts of thinking on the other.

In prior psychological work, we tested the hypothesis that these two different sorts of thinking might share opposing relationships to religious belief.  Over a series of 8 studies, we showed that although religious belief is negatively related to analytic reasoning skills (which many other labs had shown), it shares a much stronger positive relationship to measures of empathy and moral concern.  This suggests that religious belief, measured on a continuum, might emerge from the tension between empathic and analytic forms of thinking.

The current studies expanded on this prior work by examining how dogmatism – strongly holding onto one’s beliefs, even in the face of contradictory evidence – relates to measures of moral concern and analytic reasoning among individuals identifying as religious and non-religious.  The measure of dogmatism we used is neutral with respect to any particular belief system, which means that it measures dogmatism in general (rather than dogmatism towards, for instance, religious beliefs).  We found that analytic reasoning negatively relates to dogmatic tendencies in both groups.  However, the interesting part is that higher levels of dogmatism among the religious were related to higher levels of moral concern, whereas higher levels of dogmatism among the nonreligious relate to lower levels moral concern.  This is very intriguing because it suggests that religious and nonreligious individuals rely differently on these two types of cognition when forming beliefs about the world, in general.  We also found that perspective taking, which is an emotionally detached form of understanding other people’s minds, had a particularly strong negative relationship among the nonreligious.

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Long Term Memories Can Be Selectively Erased

MedicalResearch.com Interview with:
Samuel Schacher, PhD and
Jiangyuan Hu, PhD,
Department of Neuroscience
Columbia University Medical Cente
New York State Psychiatric Institute
New York, NY 10032, USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well established that learning and memory requires changes in the properties of specific neural circuits in the brain activated by the experience. The long-term storage of the memory is encoded through changes in the function of the synapses within the circuit. Synapses are sites of communication between neurons, and the changes in their function come in two varieties: increases in strength and decreases in strength. The encoding of memories typically requires some combination of these synaptic changes, synaptic plasticity, which can last a long time to contribute to long-term memory. Thus the maintenance of a memory will require the persistent change (long-term synaptic memory) in the function of specific synapses.

But memories come in different flavors. In the original experiment by Pavlov, a neutral tone, which dogs ignore, came to predict the immediate appearance of a meal. After several of these pairings, the dogs would become happily excited just with the tone. The same type of conditioning could have a negative valence – the tone could proceed a shock to one of the dog’s paw. Now the neutral tone would predict a negative stimulus and the dog would express fearful behavior just with the tone (associative learning). A non-associative form of memory would be the same types of stimuli but without the preceding neutral stimulus. At random times the animal will be given a meal or a shock. The behavior of the animal for some time will take on the positive or negative features of its environment – a contented versus depressed condition.

Each of these forms of long-term memory would be maintained by increases in the strength of specific synapses.

The questions addressed in our study published in Current Biology, based on previous work in my lab and the lab of my colleague Wayne Sossin at McGill, were:

1) Do the same molecules maintain increases in synaptic strength in the neurons of the circuit after stimuli that produce long-term classical conditioning (associative learning) and long-term sensitization (non-associative learning)?
2) If different molecules maintain the different synaptic memories, is it possible to reverse or erase the different synaptic memories by interfering with the function of the different molecules?
3) If true, can we reverse the different synaptic memories expressed in the same neuron by interfering with the function of the different molecules.

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How Do We Retrieve Speech From Our 50,000 Word Mental Dictionary?

MedicalResearch.com Interview with:

Stephanie Ries, PhD Assistant Professor School of Speech, Language, and Hearing Sciences Center for Clinical and Cognitive Neuroscience San Diego State University Director of the Laboratory for the Brain Dynamics of Language San Diego, CA

Dr. Reis

Stephanie Ries, PhD
Assistant Professor
School of Speech, Language, and Hearing Sciences
Center for Clinical and Cognitive Neuroscience
San Diego State University
Director of the Laboratory for the Brain Dynamics of Language
San Diego, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study is about how we retrieve words when we speak. We routinely do this rather effortlessly. Healthy adults can produce about 2 to 3 words per second selected among over 50,000 words in our mental dictionary. However, the neural mechanisms allowing us to do so are not well known. This process relies on two complementary mechanisms: the activation of words, and the selection of words. Our study shows that these mechanisms co-occur in time: meaning one does not end when the other starts, and in space: some brain regions, such as the posterior inferior temporal gyrus, support both mechanisms sequentially.

We were able to get an unprecedented look into the neural underpinnings of this process by studying brain activity recorded directly at the cortical surface in patients undergoing intracranial EEG monitoring for intractable epilepsy. While these patients were monitored, we asked them if they would agree to participate in our study, which consisted in naming pictures for about 10 minutes. Most of the time, they agreed. We were then able to analyze the intracranial electrical signal in relation to the pictures that were named. Such occasions are extremely rare.

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Human Behavioral Complexity Peaks At Age 25

MedicalResearch.com Interview with:
Dr. Hector Zenil

Co-director
Information Dynamics Lab
Unit of Computational Medicine, SciLifeLab
Center for Molecular Medicine
Karolinska Institute, Stockholm, Sweden 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The generation of randomness is known to be related to cognitive abilities. It has also recently been shown that animals can recur to random behaviour to outsmart other animals or overcome certain situations. Our results that humans can best outsmart computers in generating randomness at a certain age (25). The results correspond to what it was suspected, that cognitive abilities peak at an early age before declining and that no other factor was important.

We quantified a type of mathematical randomness that is known to be the true type of randomness as opposed to e.g. ‘statistical randomness’. Something that is random is difficult to describe in a succinct way. Unlike ‘statistical randomness’, ‘algorithmic randomness’ does not only produce something that appears random but also that is very difficult to generate or produce. Conversely, something that may look random for the standard of statistical randomness may not turn out to be truly random.

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