Dr. Michael Halassa[/caption]
MedicalResearch.com Interview with:
Michael M. Halassa, MD, PhD, Assistant professor
Departments of Psychiatry and Neuroscience and Physiology
The Neuroscience Institute Depts. of Psychitatry
Langone Medical Center
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Halassa: Attention is a vital aspect of our daily life and our minds are not merely a reflection of the outside world, but rather a result of careful selection of inputs that are relevant. In fact, if we indiscriminately open up our senses to what’s out there, we would be totally overwhelmed. Selecting relevant inputs and suppressing distractors is what we call attention, and as humans we are able to attend in a highly intentional manner. Meaning, we choose what to pay attention to, and we do so based on context. If you’re driving and getting directions from your GPS, you’ll be intentionally splitting your attention between your vision and hearing. Now, in one context, you might have just updated the GPS software, so you know it’s reliable; this would allow you to intentionally pay attention more to the voice coming from the GPS. In another context, the GPS software may be outdated making voice instructions unreliable. This context would prompt you to direct your attention more towards using visual navigation cues and less to the GPS voice. How the brain intentionally and dynamically directs attention based context is unknown.
The main strength of our study is that we were able to study context-dependent attention in mice. Mice are unique models because they provide genetic tools to study brain circuits. Meaning, we can turn circuits on and off very precisely in the mouse, and in a way we cannot do in other experimental animals. The inability to do these types of manipulations has been the major roadblock for progress in understanding what brain circuits mediate attention and its intentional allocation.
Because we couldn’t train mice to drive and listen to the GPS, we decided to do something much simpler. Based on context (the type of background noise in the experimental enclosure), a mouse had to select between conflicting visual and auditory stimuli in order to retrieve a milk reward. Mice love milk; it turns out, and will work tirelessly to do well on getting it. Each trial, the mouse is told ‘you need to pick the light flash’ or ‘you need to pick the auditory sweep’; these stimuli appeared on either side of the mouse randomly so the animal really had to pay attention in order to get its reward. It also had to take the context into account. We found that mice did this task, and as humans would do, they were reliant on the prefrontal cortex for determining the appropriate context. The major finding was that the prefrontal cortex changed the sensitivity of the brain to incoming stimuli (meaning, made the visual stimulus brighter when the mouse cared about vision and made the auditory stimulus louder when the mouse cared about hearing), by influencing activity in the thalamus. The thalamus is the major early relay station in the brain. The prefrontal cortex does that by instructing the brain’s switchboard, known as the thalamic reticular nucleus (TRN) to control how much visual or auditory information the thalamus was letting through. So in a sense, we discovered that executive function, represented by the prefrontal cortex, can talk to ‘attentional filters’ in the thalamus to determine what ultimately is selected from the outside environment to build our internal world.
MedicalResearch.com Interview with:
Dr. Karen Hardy
ICREA, Catalan Institution for Research and Advanced Studies
Departament de Prehistòria
Facultat de Filosofia i Lletres
Universitat Autònoma de Barcelona
Barcelona, Spain
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Hardy: There continues to be little clear agreement on what quantitatively constitutes a healthy diet. The global increase in the incidence of obesity and diet-related metabolic diseases have intensified interest in ancestral or “Palaeolithic” diets as it is clear that to a first order of approximation our physiology should be optimized to the diet that we have experienced during our evolutionary past. However, reconstructing ancestral diets is very challenging, and exactly what was eaten during the Palaeolithic remains largely unknown.
Until now, there has been a heavy focus on the role of animal fats and protein in the development of the human brain and there is little doubt that increases in meat consumption from around 3.4 million years ago, was a major driver. However, the role of carbohydrates, particularly in the form of starch-rich plant foods, has largely been overlooked. But the human brain today uses up to 25 % of the body’s energy budget and up to 60 % of blood glucose as a general rule, while pregnancy and lactation in particular, place additional demands on the body’s glucose budget. In this study we integrated multiple lines of evidence from human genetics, archaeology, anthropology, physiology, and nutrition, to hypothesise that cooked carbohydrates played an important part in the evolution of the body, and particularly the brain, over the last 800,000 years.
Our results suggest that while meat was important, brain growth is less likely to have happened without the energy obtained from carbohydrates. While cooking has also been proposed as contributing to early brain development, it has a particularly profound effect on the digestibility of starch. Furthermore, humans are unusual among primates in that they have many copies of the salivary amylase gene (average of around six salivary amylase genes, other primates have only two) leading to more efficient starch digestion. This suggests that cooking starch-rich plants and having more amylase coevolved. We don’t know exactly when the number of amylase gene copies multiplied, but genetic data suggest it was in the last million years; a timeframe that brackets archaeological evidence for cooking and when our brain size increase accelerated (around 800,000 years ago). Salivary amylases are largely ineffective on raw crystalline starch, but cooking substantially increases both their energy-yielding potential and glycemia.
MedicalResearch.com Interview with:
Helene Benveniste, MD, PhD
Professor of Anesthesiology and Radiology
Vice Chair for Research, Department of Anesthesiology
Stony Brook Medicine, Stony Brook NY
Medical Research: What is the background for this study?
Dr. Benveniste: The ‘glymphatic’ pathway is a part of the brain and is responsible for removal of waste products and excess fluid that built up especially during wakefulness. The concept was introduced by Nedergaard’s team in 2012 from University of Rochester. Importantly it has been shown to remove waste products such as soluble amyloid beta and tau protein which build up excessively in the brain of subjects afflicted with Alzheimer’s disease. The glymphatic system has been studied in detail in animal models (not yet humans) and actually is a brain-wide pathway which runs along (i.e. on the outside) of all vessels in the brain and connects to the space around the brain cells (referred to as the interstitial fluid (ISF) space). The outer part of the glymphatic network ‘tube’ is bordered by a certain type of brain cells so-called ‘astroglial’ cells which are arranged in a special way so that their endfeet cover >97% of the surface of all brain vessels. One can think of this as if the astroglial cell’s ‘endfeet’ are arranged as a donut shaped tube around all the vessels. On the astroglial endfeet there are special water channels (aquaporin-4 water channels) which are critical for how efficiently the glymphatic system can get rid of waste because it allows water to move fast through the brain tissue so as to ‘flush’ waste products out efficiently. The small gap between the astroglial endfeet also act like a ‘sieve’ so that only waste products of a certain size can access the entire pathway. Cerebrospinal fluid (CSF) circulates into the glymphatic pathway from the surface of the brain along the arteries which dives directly from the surface into the deeper part of the brain; and ultimately enters the space around the brain cells; and sweeps through it and thereby mixes with the interstitial fluid of the brain which contains waste products. The CSF-ISF mix with the waste products is then flushed out on the other ‘side’ along the veins and ultimately ends up in lymph vessels in the body and then in the blood.
It has been shown that the glymphatic pathway removes brain waste more efficiently in a state of ‘unconsciousness’ e.g. sleep or anesthesia when compared to wakefulness. Given this intriguing finding i.e. that sleeps seems to affect the waste clearance from the brain we thought that the next to look at was sleeping positions. We did these studies in anesthetized rodents.
MedicalResearch.com Interview with:
Erwin G. Van Meir, PhD
Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program
Founding Director, Graduate Program in Cancer Biology
Director, Laboratory for Molecular Neuro-Oncology
Emory University School of Medicine Atlanta GA 30322
Medical Research: What is the background for this study? What are the main findings?
Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly expressed in the brain, including in neurons, we wondered whether they might have some cognitive defect that would only be revealed under specific testing conditions. We had the mice perform in an experiment that tests their ability to orient themselves in space and memorize the location of a hidden platform in a water maze. This experiment clearly demonstrated that the Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the post synaptic density and that this was associated with an increased degradation of a key PSD protein called PSD-95.
MedicalResearch.com Interview with:
Kamen Tsvetanov, PhD
Centre for Speech, Language and the Brain
Department of Psychology
University of Cambridge
Downing Street
Cambridge, United Kingdom
Medical Research: What is the background for this study? What are the main findings?
[caption id="attachment_12706" align="alignleft" width="300"]
Brain areas with rich blood supply lower their vascular reactivity with ageing[/caption]
Dr. Tsvetanov: Older brains may be more similar to younger brains than previously thought! In our study we have shown that changes in the aging brain previously observed using functional magnetic resonance imaging (fMRI) – one of the standard ways of measuring brain activity – may be due to changes in our blood vessels, rather than changes in the activity of our nerve cells, our neurons. Given the large number of fMRI studies used to assess the aging brain, this has important consequences for understanding how the brain changes with age and it challenges current theories of ageing.
MedicalResearch.com Interview with: Dr. David T. Hsu Ph.D Department of Psychiatry, Stony Brook University, Stony Brook, NY Department of Psychiatry The Molecular & Behavioral Neuroscience Institute University of Michigan, Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Dr. Hsu: The opioid system is known for its role in...
V. Zlokovic, MD, PhD
Professor and Chair
Department of Physiology and Biophysics
Keck School of Medicine of USC.
Medical Research: What is the background for this study? What are the main findings?
Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease.
MedicalResearch.com Interview with
Gavin M. Bidelman, Ph.D.
Assistant Professor Institute for Intelligent Systems
School of Communication Sciences & Disorders
University of Memphis
Memphis, TN 38105
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Bidelman: Musical training as been shown to enhance brain function and impact behavioral skills (e.g., speech and language functions) in younger adults. In the current study, we investigated whether or not these advantages extend to older brains, which are thought to be less "plastic" (i.e., less malleable to experience/training). Older adults also often experience reduced speech recognition abilities later in life so we wanted to see if musicianship can serve as an effective means to bolster speech listening skills that decline across the lifespan.
Main findings:
1) On average, older musicians were 20% faster in identifying speech sounds behaviorally than their nonmusician peers. Interestingly, this is similar to the benefit we have observed in young people with musical training.
2) We were able to predict how well people classify/identify speech via (EEG) brain activity in both groups. However, this brain-behavior correspondence was ~2-3x better in older musicians. In other words, old musicians' brains provide a much more detailed, clean, and accurate depiction of the speech signal which is likely why they are much more sensitive to speech behaviorally.
3) We compared neural responses generated from multiple levels of the auditory system and found that musicians had more coordination (significantly higher correlations) between different regions. This implies that the "musical brain" operates more in concert than in non-musicians.
All of these findings challenge conventional views that older brain's are no longer plastic, are somehow noisier, and show poorer coordination across brain regions. In fact we show just the opposite. In older brains, musicianship does produce pervasive plasticity, provides cleaner (less noisy) representations of speech, and orchestrates more neural coordination.
MedicalResearch.com Interview with:
Dr Christos Pliatsikas PhD
Lecturer in Cognitive Psychology School of Psychology
University of Kent Canterbury Kent
Medical Research: What is the background for this study? What are the main findings?
Response: It has been proposed that lifelong bilingualism preserves the white matter structure of older bilinguals because of the increased cognitive demands that come with handling two languages for their entire life. We wanted to extend this by investigating whether active (or "immersive") bilingualism in younger late bilinguals would give similar results.
We showed increased white matter integrity (or myelination) in several white matter tracts that have also been shown to be better preserved in older lifelong bilinguals, compared to monolinguals. Based on our findings, we propose that any benefit of bilingualism to the brain structure is simply an effect of actively handling two languages without presupposing lifelong usage- our participants were only about 30 years old and had been active bilinguals for only about 7-8 years. In other words, immersive bilingualism, even in late bilinguals, leads to structural changes that can bring about benefits in older age, by assisting in the preservation of the white matter structure in the brain.
MedicalResearch.com Interview with:
György Buzsáki, M.D., Ph.D.
Biggs Professor of Neural Sciences
NYU Neuroscience Institute New York University
Langone Medical Center New York, NY 10016
Medical Research: What is the background for the NeuroGrid device?
Dr. Buzsaki: The main form of communication among neurons in the brain occurs through action potentials (‘spikes’). Understanding the mechanisms that translate spikes of individual neurons into perceptions, thoughts, and actions requires the ability to monitor large populations of neurons at the spatial and temporal resolution of their interactions.
We developed a novel, organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) with neuron-size density electrodes capable of acquiring action potential of individual neurons from the surface of the brain.
The NeuroGrid has several innovative characteristics that overcome limitations in current methods of surface recording:
(i) light-weight and conformable architecture to establish stable electrical and mechanical contacts, thereby ensuring minimal damage to underlying tissue;
(ii) efficient abiotic/biotic interface resulting in a high signal to noise ratio and the ability to resolve spikes. This is achieved by using conducting polymers as the interfacing material. Conducting polymers are mix conductors, they can conduct electronics and ionic currents hence they can efficiently transduce ion based neural activity into electronic signals
(iii) scalable neuron-size density electrodes to allow isolation and characterization of multiple individual neurons’ action potential across the cortical surface.
MedicalResearch.com Interview with:
James T. Becker, Ph.D.
Professor of Psychiatry, Psychology, and Neurology
University of Pittsburgh
Medical Research: What are the main findings of the study?
Dr. Becker: We found that people who eat baked or broiled (but not fried) fish at least once every week had significantly larger brain volumes in areas critical for memory and cognition, namely, hippocampus, precuneus, posterior cingulate cortex, and orbital frontal cortex.
Dr. Edythe D.London PhD
Professor, Departments of Psychiatry and Biobehavioral Sciences, and Molecular and Medical Pharmacology
David Geffen School of Medicine, UCLA
MedicalResearch: What are the main findings of the study?
Dr. London: Brain function related to risky decision-making was different in stimulant users (methamphetamine users) than in healthy control subjects. In healthy controls, activation in the prefrontal cortex (right dorsolateral prefrontal cortex) during risk-taking in the laboratory was sensitive to the level of risk. This sensitivity of cortical activation was weaker in stimulant users, who instead had a stronger sensitivity of striatum activation. The groups also differed in circuit-level activity (network activity) when they were not performing a task but were “at rest.” Stimulant users showed greater connectivity within the mesocorticolimbic system, a target of abused drugs. This connectivity was negatively related to sensitivity in the prefrontal cortex to risk during risky decision-making. In healthy control subjects, connectivity between the right dorsolateral prefrontal cortex and striatum was positively related to sensitivity of prefrontal cortical activation to risk during risky decision-making.
MedicalResearch.com Interview with:
Rustam Al-Shahi Salman
Professor of clinical neurology and MRC senior clinical fellow
University of Edinburgh
Honorary consultant neurologist, NHS Lothian
MedicalResearch.com: What are the main findings of the study?
Prof. Al-Shahi Salman: Patients with arteriovenous malformations (abnormal connection between arteries and veins) in the brain that have not ruptured had a lower risk of stroke or death for up to 12 years if they received conservative management of the condition compared to an interventional treatment.
Interventional treatment for brain arteriovenous malformations (bAVMs)
with procedures such as neurosurgical excision, endovascular
embolization, or stereotactic radiosurgery can be used alone or in
combination to attempt to obliterate bAVMs. Because interventions may
have complications and the untreated clinical course of unruptured
bAVMs can be benign, some patients choose conservative management (no
intervention). Guidelines have endorsed both intervention and
conservative management for unruptured brain arteriovenous malformations. Whether conservative management is superior to interventional treatment for unruptured
bAVMs is uncertain because of the lack of long-term experience,
according to background information in the article.