intellectual vanities… about close to everything

Posts Tagged ‘neurophysiology

Stress Relieve And Alcoholism

with 3 comments

A molecular brain structure that underlies feelings of stress and anxiety shows promise as a new therapeutic target for alcoholism, according to new studies by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).

In preclinical and clinical studies currently reported online, NIAAA Clinical Director Markus Heilig, M.D., Ph.D., and colleagues from the NIH, Lilly Research Laboratories, and University College in London found that a brain molecule known as the neurokinin 1 receptor, or NK1R, appears to be a central actor in stress-related drinking.

The researchers first demonstrated that NK1R plays an integral role in alcohol consumption in animals. Mice that were genetically engineered to lack NK1 receptors consumed much less alcohol than did normal mice with fully functional NK1R. Subsequently, in a small clinical study, the researchers showed that an experimental compound designed to block NK1 receptors reduced alcohol craving and improved overall wellbeing among recently detoxified alcohol-dependent individuals who had high levels of anxiety.

Using functional brain imaging, the researchers also showed that the exaggerated sensitivity to negative stimuli seen in alcoholics was dampened with the medication, while the lack of responses to pleasurable stimuli was restored.

“These findings advance our understanding of the link between stress and alcohol dependence and raise the prospect of a new class of medications for treating alcoholism,” adds NIAAA Director Ting-Kai Li, M.D.

Relapse to uncontrolled drinking after periods of sobriety is a defining characteristic of alcoholism and is often triggered by stress.

“The driving force behind dependent individuals’ alcohol use transitions from what we call reward craving to relief craving,” explains Dr. Heilig. “By the time people seek treatment for alcoholism, the pleasurable or rewarding effects of the drug are gone for most patients. Instead, alcohol-dependent individuals often feel low, anxious and are sensitive to stress, and they use alcohol to relieve these bad feelings.”

Previous studies have shown that a brain chemical known as Substance P (SP) is released in response to stress, produces symptoms of anxiety, and binds preferentially to NK1R. SP and NK1R are highly expressed in brain areas involved in stress responses and drug reward. Studies have also shown that anxiety and stress responses can be reduced in both animals and humans by inactivating NK1R. Such studies suggest that interfering with NK1R function could possibly subvert any role it might play in stress-related alcohol consumption.

Dr. Heilig and his colleagues conclude that if further studies establish activation of the SP-NK1R system as a consistent feature of alcohol dependence, compounds that block NK1R may have considerable potential for treating alcoholism, and potentially other addictions.
Science. 2008 Feb 14 [Epub ahead of print]

Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism.

George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, Peng X, Kielbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M.

Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.

Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. Here, we investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall wellbeing, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment target in alcoholism.

Advertisements

Written by huehueteotl

February 28, 2008 at 9:29 pm

Neural Basis Of ‘Number Sense’ In Young Infants

leave a comment »

Behavioral experiments indicate that infants aged 4½ months or older possess an early “number sense” that allows them to detect changes in the number of objects.
Distinct cerebral pathways for object identity and number have been identified in the brain of human infants. (Credit: Izard V, Dehaene-Lambertz G, Dehaene S)

However, the neural basis of this ability was previously unknown.

In new research, Véronique Izard, Ghislaine Dehaene-Lambertz, and Stanislas Dehaene provide brain imaging evidence showing that very young infants are sensitive to both the number and identity of objects, and these pieces of information are processed by distinct neural pathways.

The authors recorded the electrical activity evoked by the brain on the surface of the scalp as 3-months-old infants were watching images of objects. The number or identity of objects occasionally changed.

The authors found that the infant brain responds to both changes, but in different brain regions, which map onto the same regions that activate in adults. These results show that very young infants are sensitive to small changes in number, and the brain organization that underlies the perception of object number and identity are established early during development.

PLoS Biology Vol. 6, No. 2, e11 doi:10.1371/journal.pbio.0060011

Distinct Cerebral Pathways for Object Identity and Number in Human Infants

Izard V, Dehaene-Lambertz G, Dehaene S 

All humans, regardless of their culture and education, possess an intuitive understanding of number. Behavioural evidence suggests that numerical competence may be present early on in infancy. Here, we present brain-imaging evidence for distinct cerebral coding of number and object identity in 3-mo-old infants. We compared the visual event-related potentials evoked by unforeseen changes either in the identity of objects forming a set, or in the cardinal of this set. In adults and 4-y-old children, number sense relies on a dorsal system of bilateral intraparietal areas, different from the ventral occipitotemporal system sensitive to object identity. Scalp voltage topographies and cortical source modelling revealed a similar distinction in 3-mo-olds, with changes in object identity activating ventral temporal areas, whereas changes in number involved an additional right parietoprefrontal network. These results underscore the developmental continuity of number sense by pointing to early functional biases in brain organization that may channel subsequent learning to restricted brain areas.

Written by huehueteotl

February 11, 2008 at 9:39 am

Seasonal Changes in Mood and Behavior Are Linked to Obesity

leave a comment »

Obesity is a public health problem worldwide, officials even using the term of an obesity epidemic. Meanwhile, it is increasingly accepted that obesity is a consequence of combined genetic and environmental factors. A new finnish study could pove that a defective circadian clockwork is associated with obesity and metabolic syndrome.

https://i2.wp.com/www.blockmd.com/images/BodyClock.gif

8028 individuals attended a nationwide health examination survey in Finland. Participants were assessed  for metabolic syndrome and for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors.

“Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome”, the researchers explain.

Rintamäki R, Grimaldi S, Englund A, Haukka J, Partonen T, et al. (2008)

Seasonal Changes in Mood and Behavior Are Linked to Metabolic Syndrome.

PLoS ONE 3(1): e1482. doi:10.1371/journal.pone.0001482

Background

Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome.

Methodology and Principal Findings

8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors.

Conclusions and Significance

Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome.

Written by huehueteotl

February 7, 2008 at 12:50 pm

Obesity Wired In The Brain?

leave a comment »

A predisposition for obesity might be wired into the brain from the start, suggests a new study of rats.

Rats selectively bred to be prone to obesity show abnormalities in a part of the brain critical for appetite control, the researchers found. Specifically, the researchers show that the obese rats harbor defects in neurons of the arcuate nucleus (ARH) of the hypothalamus, which leaves their brains less responsive to the hunger-suppressing hormone leptin.

“The neurodevelopmental differences in these animals can be seen as early as the first week,” said Sebastien Bouret of the University of Southern California. “The results show that obesity can be wired into the brain from early life. The three-million-dollar question now is how to get around this problem.”

It is increasingly accepted that obesity results from a combination of genetic and environmental factors, the researchers said. Rodent models of obesity can provide valuable insights into the biological processes underlying the development of obesity in humans. The “diet-induced obese” (DIO) rats used in the current study are particularly suited to the task, according to Bouret, because their tendency to become overweight shares several features with human obesity, including the contribution of many genes.

A predisposition for obesity might be wired into the brain from the start, suggests a new study. (Credit: iStockphoto/Ekaterina Monakhova)

Previous studies had suggested that the brains of DIO rats are insensitive to leptin, the researchers added. Circulating leptin, produced by fat tissue, acts as a signal to the brain about the body’s energy status. Leptin is also critical for the initial development of ARH neurons.

In the new study, the researchers examined the obesity-prone rats for signs of abnormal brain development. They found that the animals’ brains had fewer neural projections from the ARH, a deficiency that persisted into adulthood. Those projections are needed to relay the leptin signal received by the ARH to other parts of the hypothalamus, Bouret said.

The researchers found further evidence that those changes in brain wiring stem from a reduced responsiveness of the brain to leptin’s action during development.

“It seems [in the case of these rats] that appetite and obesity are built into the brain,” Bouret said. While their condition might be ameliorated by exercising and eating right, he added, the findings suggest that the propensity to gain weight can’t be reversed.

But there is hope yet. It’s possible that treatments delivered during a critical early period of development might be capable of rewiring the brain, Bouret said.

Cell Metab. 2008 Feb;7(2):179-85.
Hypothalamic neural projections are permanently disrupted in diet-induced obese rats.
Neuroscience Program, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA; Inserm, U837, Jean-Pierre Aubert Research Center, Université Lille 2, 59045 Lille, France.The arcuate nucleus of the hypothalamus (ARH) is a key component of hypothalamic pathways regulating energy balance, and leptin is required for normal development of ARH projections. Diet-induced obesity (DIO) has a polygenic mode of inheritance, and DIO individuals develop the metabolic syndrome when a moderate amount of fat is added to the diet. Here we demonstrate that rats selectively bred to develop DIO, which are known to be leptin resistant before they become obese, have defective ARH projections that persist into adulthood. Furthermore, the ability of leptin to activate intracellular signaling in ARH neurons in vivo and to promote ARH neurite outgrowth in vitro is significantly reduced in DIO neonates. Thus, animals that are genetically predisposed toward obesity display an abnormal organization of hypothalamic pathways involved in energy homeostasis that may be the result of diminished responsiveness of ARH neurons to the trophic actions of leptin during postnatal development.

 

Written by huehueteotl

February 7, 2008 at 9:52 am

Checking One Voice In A Noisy Room? New Findings On Selectively Interpreting Sounds

with one comment

Scientists at Cold Spring Harbor Laboratory (CSHL) have reported new findings about how the mammalian brain interprets and fashions representations of sound that may help explain how we are able to focus on one particular sound among many in noisy environments such as offices or cocktail parties.

https://i0.wp.com/lwosterman.members.winisp.net/sinewave.png

Neurons in the brain’s auditory cortex interpret incoming sound signals and send them to the rest of the nervous system, in the brain and spinal cord. Using rats, the CSHL team discovered that a very small minority of available auditory neurons react strongly when exposed to any specific sound.

“This finding challenges the standard model of sound representations in the auditory cortex, which predicts that neural representations of stimuli often engage a large fraction of neurons,” said Anthony Zador, Ph.D., CSHL professor and corresponding author of a new research paper.*

The researchers used a new technique called “in vivo cell-attached patch clamp recording” which measures the reaction of individual neurons. This recording technique samples neurons in a fair and unbiased way, unlike traditional approaches, which favored the largest and most active neurons. Using this technique, the team found that only 5% of neurons in the auditory cortex had a “high firing rate” when receiving a range of sounds of varying length, frequency, and volume. The experiment included white noise and natural animal sounds.

The team’s objective was to quantify the relative contributions of different sub-populations of neurons in response to the range of sounds. Most of what is known about the auditory cortex of the mammalian brain comes from studies of the anesthetized cortex. The results of the experiments reported today are important partly because they measure the response of neurons in rats that were not anesthetized. In animals that are awake, it’s possible to measure the response over an interval of time to one sound among many that are co-occurring.

This is the approach the Zador lab has taken to explain “selective attention,” or what Dr. Zador calls “the cocktail party problem.” Half of the neurons measured in the reported experiments showed no reaction at all to incoming stimuli. The researchers hypothesize that each neuron in the auditory cortex may have an “optimal stimulus” to which it is particularly sensitized.

“Your entire sensory apparatus is there to make successful representations of the outside world,” said Dr. Zador, who is director of the CSHL Swartz Center for Computational Neuroscience. “Sparse representations may make sensory stimuli easier to recognize and remember.” Recognizing the brain’s ability to distinguish “optimal stimuli” could help scientists find ways to improve how sounds are learned. Prior research has already yielded similar results when measuring sight, movement, and smell. This is the first evidence of a correlation between sparse representations and hearing.

“The goal of sensory processing is to take a signal, like a sound or a vision, from your environment and use it to drive behavior,” said Dr. Zador. “The brain needs to recognize and learn about these inputs in order to survive.”

PLoS Biol 6(1): e16 doi:10.1371/journal.pbio.0060016

Sparse Representation of Sounds in the Unanesthetized Auditory Cortex

Tomáš Hromádka1, Michael R. DeWeese2, Anthony M. Zador3*

1 Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold Spring Harbor, New York, United States of America, 2 Department of Physics and Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America, 3 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America

How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli) in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second) in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second). At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons.

Written by huehueteotl

January 30, 2008 at 6:42 pm

No Use For Transcranial Magnetic Stimulation In Treatment Of Bulimia Nervosa?

leave a comment »

A group of investigators of the Innsbruck University (Austria) reports on a new modality of treatment for bulimia nervosa, transcranial magnetic stimulation. Transcranial magnetic stimulation is a non-invasive, neurophysiological method, which affects cortical neurons with a short magnetic pulse.
http://nuttre.files.wordpress.com/2007/07/la_bulimia_1.jpg

Bulimia nervosa (BN) is often associated with depressive symptoms and treatment with antidepressants has shown positive effects. A shared deficient serotonergic transmission was postulated for both syndromes. The left dorsolateral prefrontal cortex was argued to regulate eating behaviour and to be dysfunctional in eating disorders.So far, fourteen women meeting DSM-IV criteria for BN were included in a preliminary randomised placebo-controlled double-blind trial. In order to exclude patients highly responsive to placebo, all patients were first submitted to a one-week sham treatment. Randomisation was followed by 3 weeks of active treatment or sham stimulation. As the main outcome criterion the change in binges and purges was defined. Secondary outcome variables were the decrease of the Hamilton Depression Rating Scale (HDRS), the Beck Depression Inventory (BDI) and the Yale-Brown Obsessive Compulsive Scale (YBOCS) over time.

The average number of binges per day declined significantly between baseline and the end of treatment in the two groups. There was no significant difference between sham and active stimulation in terms of purge behaviour, BDI, HDRS and YBOCS over time.

These preliminary results indicate that repetitive transcranial magnetic stimulation (rTMS) in the treatment of BN does not exert additional benefit over placebo. A larger number of patients might clarify a further role of rTMS in the treatment of BN.

Psychother Psychosom. 2008;77(1):57-60. Epub 2007 Dec 14.
Repetitive transcranial magnetic stimulation in bulimia nervosa: preliminary results of a single-centre, randomised, double-blind, sham-controlled trial in female outpatients.

Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria. Michaela.Walpoth@i-med.ac.at

BACKGROUND: Bulimia nervosa (BN) is often associated with depressive symptoms and treatment with antidepressants has shown positive effects. A shared deficient serotonergic transmission was postulated for both syndromes. The left dorsolateral prefrontal cortex was argued to regulate eating behaviour and to be dysfunctional in eating disorders. METHODS: Fourteen women meeting DSM-IV criteria for BN were included in a randomised placebo-controlled double-blind trial. In order to exclude patients highly responsive to placebo, all patients were first submitted to a one-week sham treatment. Randomisation was followed by 3 weeks of active treatment or sham stimulation. As the main outcome criterion we defined the change in binges and purges. Secondary outcome variables were the decrease of the Hamilton Depression Rating Scale (HDRS), the Beck Depression Inventory (BDI) and the Yale-Brown Obsessive Compulsive Scale (YBOCS) over time. RESULTS: The average number of binges per day declined significantly between baseline and the end of treatment in the two groups. There was no significant difference between sham and active stimulation in terms of purge behaviour, BDI, HDRS and YBOCS over time. CONCLUSION: These preliminary results indicate that repetitive transcranial magnetic stimulation (rTMS) in the treatment of BN does not exert additional benefit over placebo. A larger number of patients might clarify a further role of rTMS in the treatment of BN. 2008 S. Karger AG, Basel

Written by huehueteotl

January 22, 2008 at 4:17 pm

Overweight People May Not Know When They’ve Had Enough

with 2 comments

Researchers at the U.S. Department of Energy’s Brookhaven National Laboratory have found new clues to why some people overeat and gain weight while others don’t. Examining how the human brain responds to “satiety” messages delivered when the stomach is in various stages of fullness, the scientists have identified brain circuits that motivate the desire to overeat. Treatments that target these circuits may prove useful in controlling chronic overeating, according to the authors.
Overweight
“By simulating feelings of fullness with an expandable balloon we saw the activation of different areas of the brain in normal weight and overweight people,” said lead author Gene-Jack Wang of Brookhaven Lab’s Center for Translational Neuroimaging. The overweight subjects had less activation in parts of the brain that signal satiety in normal weight subjects. The overweight subjects were also less likely than normal weight subjects to report satiety when their stomachs were moderately full. “These findings provide new evidence for why some people will continue to eat despite having eaten a moderate-size meal,” said Wang.Wang and colleagues studied the brain metabolism of 18 individuals with body mass indices (BMI) ranging from 20 (low/normal weight) to 29 (extremely overweight/borderline obese). Each study participant swallowed a balloon, which was then filled with water, emptied, and refilled again at volumes that varied between 50 and 70 percent. During this process, the researchers used functional magnetic resonance imaging (fMRI) to scan the subjects’ brains. Subjects were also asked throughout the study to describe their feelings of fullness. The higher their BMI, the lower their likelihood of saying they felt “full” when the balloon was inflated 70 percent.

One notable region of the brain – the left posterior amygdala – was activated less in the high-BMI subjects, while it was activated more in their thinner counterparts. This activation was turned “on” when study subjects reported feeling full. Subjects who had the highest scores on self-reports of hunger had the least activation in the left posterior amygdala.

https://i1.wp.com/www.neilslade.com/gifs/amygdala2.jpg

“This study provides the first evidence of the connection of the left amygdala and feelings of hunger during stomach fullness, demonstrating that activation of this brain region suppresses hunger,” said Wang. “Our findings indicate a potential direction for treatment strategies – be they behavioral, medical or surgical — targeting this brain region.”

The scientists also looked at a range of hormones that regulate the digestive system, to see whether they played a role in responding to feelings of fullness. Ghrelin, a hormone known to stimulate the appetite and cause short-term satiety, showed the most relevance. Researchers found that individuals who had greater increases in ghrelin levels after their stomachs were moderately full also had greater activation of the left amygdala. “This indicates that ghrelin may control the reaction of the amygdala to satiety signals sent by the stomach,” said Wang.

https://i0.wp.com/www.phoenixpeptide.com/catalog/upload/pnxnews/pnxnews_000000062/notes/bio-ghrelin.jpg

Neuroimage. 2007 Nov 22 [Epub ahead of print]
Gastric distention activates satiety circuitry in the human brain.

Brookhaven National Laboratory, Upton, NY, USA; Mt. Sinai School of Medicine, NY, USA.

Gastric distention during meal ingestion activates vagal afferents, which send signals from the stomach to the brain and result in the perception of fullness and satiety. Distention is one of the mechanisms that modulates food intake. We measured regional brain activation during dynamic gastric balloon distention in 18 health subjects using functional magnetic resonance imaging and the blood oxygenation level-dependent (BOLD) responses. The BOLD signal was significantly changed by both inflow and outflow changes in the balloon’s volume. For lower balloon volumes, water inflow was associated with activation of sensorimotor cortices and right insula. The larger volume condition additionally activated left posterior amygdala, left posterior insula and the left precuneus. The response in the left amygdala and insula was negatively associated with changes in self-reports of fullness and positively with changes in plasma ghrelin concentration, whereas those in the right amygdala and insula were negatively associated with the subject’s body mass index. The widespread activation induced by gastric distention corroborates the influence of vagal afferents on cortical and subcortical brain activity. These findings provide evidence that the left amygdala and insula process interoceptive signals of fullness produced by gastric distention involved in the controls of food intake.

Written by huehueteotl

January 16, 2008 at 4:19 pm