intellectual vanities… about close to everything

The cognitive strategies humans use to regulate emotions can determine both neurological and physiological responses to potential rewards, a team of New York University and Rutgers University neuroscientists has discovered. The findings, reported in the most recent issue of the journal Nature Neuroscience, shed light on how the regulation of emotions may influence decision making.

Previous research has demonstrated these strategies can alter responses to negative events. However, less understood is whether such strategies can also efficiently regulate expectations of a future reward or a desired outcome. Scientists have already determined that the expectation of a potential reward brings about positive feelings and aids recognizing environmental cues that predict future rewards. Central to this process is the role of the striatum, a multi-faceted structure in the brain that is involved in reward processing–and which is especially engaged when potential rewards are predicted or anticipated.

However, the striatum signal is not always beneficial. Its activity also correlates with drug-specific cravings, most likely increasing urges to partake in risk-seeking behavior in the pursuit of rewards that are detrimental. Therefore, understanding how to regulate or control the positive feelings associated with reward expectation is an important line of inquiry.

The NYU study was conducted by a team of researchers from the laboratory of NYU Professor Elizabeth Phelps, who co-authored the work with Mauricio R. Delgado, now a professor at Rutgers University, and M. Meredith Gillis, an NYU graduate student. They sought to better understand the influence of emotional regulation strategies on the physiological and neural processes relevant to expectations of reward.

The study’s subjects were presented with two conditioned stimuli, a blue and a yellow square that either predicted or did not predict a potential monetary reward. Prior to each trial, participants were also given a written cue that instructed them to either respond to the stimulus (”think of the meaning of the blue square, such as a potential reward”) or regulate their emotional response to the stimulus (”think of something blue in nature that calms you down, such as the ocean”).

Skin conductance responses (SCRs) of the participants were taken at the beginning of each conditioned stimulus. These served as a behavioral measure of physiological reaction potentially related to reward anticipation.

The results showed that the participants’ emotion regulation strategies could influence physiological and neural responses relevant to the expectation of reward. Specifically, results from the SCRs revealed that the subjects’ emotion regulation strategies decreased arousal that was linked to the anticipation of a potential reward.

“Our findings demonstrated that emotion regulation strategies can successfully curb physiological and neural responses associated with the expectation of reward,” said Delgado. “This is a first step to understanding how our thoughts may effectively control positive emotions and eventual urges that may arise, such as drug cravings.”

Nature Neuroscience Published online: 29 June 2008 | doi:10.1038/nn.2141

Brief Communication abstract

Regulating the expectation of reward via cognitive strategies

Mauricio R Delgado, M Meredith Gillis, Elizabeth A Phelps

Previous emotion regulation research has been successful in altering aversive emotional reactions. It is unclear, however, whether such strategies can also efficiently regulate expectations of reward arising from conditioned stimuli, which can at times be maladaptive (for example, drug cravings). Using a monetary reward-conditioning procedure with cognitive strategies, we observed attenuation in both the physiological (skin conductance) and neural correlates (striatum) of reward expectation as participants engaged in emotion regulation.

Thanks to salt and hot chili peppers, researchers have found a calculus-computing center that tells a roundworm to go forward toward dinner or turn to broaden the search.

A spike in salt concentration in ASEL (left neuron) activates expression that leads a worm to proceed in a straight line. A dip in salt levels in ASER (right neuron) turns on a negative reaction that tells a worm to change to a turning movement to look around. (Credit: Graphic courtesy of Shawn Lockery)

These behavior-driving calculations, according to a paper published in the July 3 issue of the journal Nature, are done “in a tiny, specialized computer inside a primitive roundworm,” says principal investigator Shawn Lockery, a University of Oregon biologist and member of the UO Institute of Neuroscience.

In their paper, the researchers documented how two related, closely located chemosensory neurons, acting in tandem, regulate behavior. The left neuron controls an on switch, while the opposing right one an off switch. These sister neurons are situated much like the two nostrils or two eyes of mammals. Together these neurons are known as ASE for antagonistic sensory cues.

It’s possible, Lockery said, that the discovery someday could help research aimed at treating at least some of the 200,000 people in the United States who annually seek medical treatment, according to records of the National Institutes of Health, for problems involving taste and smell.

“This computer does some nice calculus, differentiating the rate of change of the strength of various tastes,” Lockery said. “The worm uses this information to find food and to avoid poisons.”

Lockery and colleagues predicted the existence of a derivative-crunching mechanism in the Journal of Neuroscience in 1999 based on findings that nematodes change directions based on taste and smell.

“In effect, they have two nostrils or two tongues but they are so close together that it is really like having one nostril or one tongue, and yet they find their way around quite effectively,” Lockery said. “We knew from behavioral experiments that nematodes were doing the same thing that humans were doing, but only from the view of behavioral responses. We didn’t know what was going on in the brain.”

To get there, Lockery and colleagues used new imaging and molecular tools, along with some genetic engineering of their worms.

In one experiment, these chemosensory neurons carried a fluorescent protein that changed color based on neuronal activity. In another experiment, the neurons carried receptor proteins that recognize capsaicin, the active component in chili peppers.

Researchers found that when concentrations of salt were high, fluorescent proteins change from blue to yellow, showing that the left neuron (ASEL) was active as the worms continued forward movement. When salt levels were reduced, the right neuron (ASER) activated but generated a different behavior; the worms began a turning, or searching, motion.

“At this point, we wanted to know if these neurons really are controlling behavior. If ASEL really signals that things are getting better, then, if you could artificially activate ASEL the animals ought to go straight like a human going directly toward the pizza,” Lockery said. “Conversely, if you activate the ASER the animals ought to turn to find their goal.”

Such was the case, according to the capsaicin-receptor experiment. When the pepper ingredient was spread on turning worms with receptor proteins in the left neuron, they straightened their motion. Likewise, capsaicin applied to worms with the receptors in their right neurons caused them to change from turning motion to forward crawling.

“We have discovered a tiny, specialized computer inside a primitive round worm,” Lockery said. “The computer calculates the rate of change of the strengths, or concentrations, of various tastes. The worm uses this information to find food and to avoid poisons.”

Evidence for such on and off switching cells in other chemosensory networks of mammals, he added, “There are strong indications that a similar device exists in the human nervous system.”

Nature 454, 114 - 117 (03 Jul 2008), doi: 10.1038/nature06927, Letters to Editor

Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis

Hiroshi Suzuki, Tod R. Thiele, Serge Faumont, Marina Ezcurra, Shawn R. Lockery, William R. Schafer

Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria¹, involves a random walk biased by the time derivative of attractant concentration, but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons (ASEL and ASER) are ablated, indicating that this pair has a dominant role⁴. Although these neurons are left–right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference. Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON-cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON–OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion (runs) whereas ASER promotes direction changes (turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis. Evidence for ON and OFF cells in other chemosensory networks suggests that this motif may be common in animals that navigate by taste and smell.

New research at UT Southwestern Medical Center may explain why some people who are stressed or depressed overeat. While levels of the so-called “hunger hormone” ghrelin are known to increase when a person doesn’t eat, findings by UT Southwestern scientists suggest that the hormone might also help defend against symptoms of stress-induced depression and anxiety.

“Our findings in mice suggest that chronic stress causes ghrelin levels to go up and that behaviors associated with depression and anxiety decrease when ghrelin levels rise. An unfortunate side effect, however, is increased food intake and body weight,” said Dr. Jeffrey Zigman, assistant professor of internal medicine and psychiatry at UT Southwestern and senior author of a study appearing online today and in a future print edition of Nature Neuroscience.

Dr. Michael Lutter, instructor of psychiatry at UT Southwestern and lead author of the study, said, “Our findings support the idea that these hunger hormones don’t do just one thing; rather, they coordinate an entire behavioral response to stress and probably affect mood, stress and energy levels.”

It is known that fasting causes ghrelin to be produced in the gastrointestinal tract, and that the hormone then plays a role in sending hunger signals to the brain. Research groups including Dr. Zigman’s have suggested that blocking the body’s response to ghrelin signals might be one way to help control weight by decreasing food intake and increasing energy expenditure.

“However, this new research suggests that if you block ghrelin signaling, you might actually increase anxiety and depression, which would be bad,” Dr. Zigman said.

To determine how ghrelin affects mood, Dr. Zigman and his colleagues restricted the food intake of laboratory mice for 10 days. This caused their ghrelin levels to quadruple. As compared to the control mice, which were allowed free access to food, the calorie-restricted mice displayed decreased levels of anxiety and depression when subjected to mazes and other standard behavior tests for depression and anxiety.

In addition, mice genetically engineered to be unable to respond to ghrelin were also fed a restricted-calorie diet. Unlike their calorie-restricted wild-type counterparts, these mice did not experience the antidepressant-like or anti-anxiety-like effects.

To test whether ghrelin could regulate depressive symptoms brought on by chronic stress, the researchers subjected mice to daily bouts of social stress, using a standard laboratory technique that induces stress by exposing normal mice to very aggressive “bully” mice. Such animals have been shown to be good models for studying depression in humans.

The researchers stressed both wild-type mice and altered mice that were unable to respond to ghrelin. They found that after experiencing stress, both types of mice had significantly elevated levels of ghrelin that persisted at least four weeks after their last defeat encounter. The altered mice, however, displayed significantly greater social avoidance than their wild-type counterparts, indicating an exacerbation of depression-like symptoms. They also ate less than the wild-type mice.

Dr. Zigman said the findings make sense when considered from an evolutionary standpoint.

Until modern times, the one common human experience was securing enough food to prevent starvation. Our hunter-gatherer ancestors needed to be as calm and collected as possible when it was time to venture out in search of food, or risk becoming dinner themselves, Dr. Zigman said, adding that the anti-anxiety effects of hunger-induced ghrelin may have provided a survival advantage.

Dr. Lutter said the findings might be relevant in understanding conditions such as anorexia nervosa.

“We’re very interested to see whether ghrelin treatment could help people with anorexia nervosa, with the idea being that in a certain population, calorie restriction and weight loss could have an antidepressant effect and could be reinforcing for this illness,” Dr. Lutter said.

In future studies, the researchers hope to determine which area in the brain ghrelin may be acting on to cause these antidepressant-like effects.

Nature Neuroscience (15 Jun 2008), doi: 10.1038/nn.2139, Brief Communications

We found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test. Moreover, chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat. Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress.

Drink coffee to send a wake-up call to the brain? Or just smell its rich, warm aroma? An international group of scientists is reporting some of the first evidence that simply inhaling coffee aroma alters the activity of genes in the brain.

In experiments with laboratory rats, they found that coffee aroma orchestrates the expression of more than a dozen genes and some changes in protein expressions, in ways that help reduce the stress of sleep deprivation.

Han-Seok Seo and colleagues point out that hundreds of studies have been done on the ingredients in coffee, including substances linked to beneficial health effects. “There are few studies that deal with the beneficial effects of coffee aroma,” they note. “This study is the first effort to elucidate the effects of coffee bean aroma on the sleep deprivation-induced stress in the rat brain.”

In an effort to begin filling that gap, they allowed lab rats to inhale coffee aroma, including some rats stressed by sleep deprivation. The study then compared gene and protein expressions in the rats’ brains. Rats that sniffed coffee showed different levels of activity in 17 genes. Thirteen of the genes showed differential mRNA expression between the stress group and the stress with coffee group, including proteins with healthful antioxidant activity known to protect nerve cells from stress-related damage.

ASAP J. Agric. Food Chem., ASAP Article, 10.1021/jf8001137
Web Release Date: June 3, 2008

The aim of this study was 2-fold: (i) to demonstrate influences of roasted coffee bean aroma on rat brain functions by using the transcriptomics and proteomics approaches and (ii) to evaluate the impact of roasted coffee bean aroma on stress induced by sleep deprivation. The aroma of the roasted coffee beans was administered to four groups of adult male Wistar rats: 1, control group; 2, 24 h sleep deprivation-induced stress group (the stress group); 3, coffee aroma-exposed group without stress (the coffee group); and 4, the stress with coffee aroma group (the stress with coffee group). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of some known genes responsive to aroma or stress was performed using total RNA from these four groups. A total of 17 selected genes of the coffee were differently expressed over the control. Additionally, the expression levels of 13 genes were different between the stress group and the stress with coffee group: Up-regulation was found for 11 genes, and down-regulation was seen for two genes in the stress with coffee group. We also looked to changes in protein profiles in these four samples using two-dimensional (2D) gel electrophoresis; 25 differently expressed gel spots were detected on 2D gels stained by silver nitrate. Out of these, a total of nine proteins were identified by mass spectrometry. Identified proteins belonged to five functional categories: antioxidant; protein fate; cell rescue, defense, and virulence; cellular communication/signal transduction mechanism; and energy metabolism. Among the differentially expressed genes and proteins between the stress and the stress with coffee group, NGFR, trkC, GIR, thiol-specific antioxidant protein, and heat shock 70 kDa protein 5 are known to have antioxidant or antistress functions. In conclusion, the roasted coffee bean aroma changes the mRNA and protein expression levels of the rat brain, providing for the first time clues to the potential antioxidant or stress relaxation activities of the coffee bean aroma.

Coffee’s Aroma Kick-starts Genes In The Brain

ScienceDaily (Jun. 16, 200 — Drink coffee to send a wake-up call to the brain? Or just smell its rich, warm aroma? An international group of scientists is reporting some of the first evidence that simply inhaling coffee aroma alters the activity of genes in the brain.

In experiments with laboratory rats, they found that coffee aroma orchestrates the expression of more than a dozen genes and some changes in protein expressions, in ways that help reduce the stress of sleep deprivation.

Han-Seok Seo and colleagues point out that hundreds of studies have been done on the ingredients in coffee, including substances linked to beneficial health effects. “There are few studies that deal with the beneficial effects of coffee aroma,” they note. “This study is the first effort to elucidate the effects of coffee bean aroma on the sleep deprivation-induced stress in the rat brain.”

In an effort to begin filling that gap, they allowed lab rats to inhale coffee aroma, including some rats stressed by sleep deprivation. The study then compared gene and protein expressions in the rats’ brains. Rats that sniffed coffee showed different levels of activity in 17 genes. Thirteen of the genes showed differential mRNA expression between the stress group and the stress with coffee group, including proteins with healthful antioxidant activity known to protect nerve cells from stress-related damage.

ASAP J. Agric. Food Chem., ASAP Article, 10.1021/jf8001137
Web Release Date: June 3, 2008

The aim of this study was 2-fold: (i) to demonstrate influences of roasted coffee bean aroma on rat brain functions by using the transcriptomics and proteomics approaches and (ii) to evaluate the impact of roasted coffee bean aroma on stress induced by sleep deprivation. The aroma of the roasted coffee beans was administered to four groups of adult male Wistar rats: 1, control group; 2, 24 h sleep deprivation-induced stress group (the stress group); 3, coffee aroma-exposed group without stress (the coffee group); and 4, the stress with coffee aroma group (the stress with coffee group). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of some known genes responsive to aroma or stress was performed using total RNA from these four groups. A total of 17 selected genes of the coffee were differently expressed over the control. Additionally, the expression levels of 13 genes were different between the stress group and the stress with coffee group: Up-regulation was found for 11 genes, and down-regulation was seen for two genes in the stress with coffee group. We also looked to changes in protein profiles in these four samples using two-dimensional (2D) gel electrophoresis; 25 differently expressed gel spots were detected on 2D gels stained by silver nitrate. Out of these, a total of nine proteins were identified by mass spectrometry. Identified proteins belonged to five functional categories: antioxidant; protein fate; cell rescue, defense, and virulence; cellular communication/signal transduction mechanism; and energy metabolism. Among the differentially expressed genes and proteins between the stress and the stress with coffee group, NGFR, trkC, GIR, thiol-specific antioxidant protein, and heat shock 70 kDa protein 5 are known to have antioxidant or antistress functions. In conclusion, the roasted coffee bean aroma changes the mRNA and protein expression levels of the rat brain, providing for the first time clues to the potential antioxidant or stress relaxation activities of the coffee bean aroma.

Scientists at Carnegie Mellon University have taken an important step toward understanding how the human brain codes the meanings of words by creating the first computational model that can predict the unique brain activation patterns associated with names for things that you can see, hear, feel, taste or smell.

Researchers previously have shown that they can use functional magnetic resonance imaging (fMRI) to detect which areas of the brain are activated when a person thinks about a specific word. A Carnegie Mellon team has taken the next step by predicting these activation patterns for concrete nouns — things that are experienced through the senses — for which fMRI data does not yet exist.

The work could eventually lead to the use of brain scans to identify thoughts and could have applications in the study of autism, disorders of thought such as paranoid schizophrenia, and semantic dementias such as Pick’s disease.

The team, led by computer scientist Tom M. Mitchell and cognitive neuroscientist Marcel Just, constructed the computational model by using fMRI activation patterns for 60 concrete nouns and by statistically analyzing a set of texts totaling more than a trillion words, called a text corpus. The computer model combines this information about how words are used in text to predict the activation patterns for thousands of concrete nouns contained in the text corpus with accuracies significantly greater than chance.

The findings are being published in the May 30 issue of the journal Science.

“We believe we have identified a number of the basic building blocks that the brain uses to represent meaning,” said Mitchell, who heads the School of Computer Science’s Machine Learning Department. “Coupled with computational methods that capture the meaning of a word by how it is used in text files, these building blocks can be assembled to predict neural activation patterns for any concrete noun. And we have found that these predictions are quite accurate for words where fMRI data is available to test them.”

Just, a professor of psychology who directs the Center for Cognitive Brain Imaging, said the computational model provides insight into the nature of human thought. “We are fundamentally perceivers and actors,” he said. “So the brain represents the meaning of a concrete noun in areas of the brain associated with how people sense it or manipulate it. The meaning of an apple, for instance, is represented in brain areas responsible for tasting, for smelling, for chewing. An apple is what you do with it. Our work is a small but important step in breaking the brain’s code.”

In addition to representations in these sensory-motor areas of the brain, the Carnegie Mellon researchers found significant activation in other areas, including frontal areas associated with planning functions and long-term memory. When someone thinks of an apple, for instance, this might trigger memories of the last time the person ate an apple, or initiate thoughts about how to obtain an apple.

“This suggests a theory of meaning based on brain function,” Just added.

In the study, nine subjects underwent fMRI scans while concentrating on 60 stimulus nouns — five words in each of 12 semantic categories including animals, body parts, buildings, clothing, insects, vehicles and vegetables.

To construct their computational model, the researchers used machine learning techniques to analyze the nouns in a trillion-word text corpus that reflects typical English word usage. For each noun, they calculated how frequently it co-occurs in the text with each of 25 verbs associated with sensory-motor functions, including see, hear, listen, taste, smell, eat, push, drive and lift. Computational linguists routinely do this statistical analysis as a means of characterizing the use of words.

These 25 verbs appear to be basic building blocks the brain uses for representing meaning, Mitchell said.

By using this statistical information to analyze the fMRI activation patterns gathered for each of the 60 stimulus nouns, they were able to determine how each co-occurrence with one of the 25 verbs affected the activation of each voxel, or 3-D volume element, within the fMRI brain scans.

To predict the fMRI activation pattern for any concrete noun within the text corpus, the computational model determines the noun’s co-occurrences within the text with the 25 verbs and builds an activation map based on how those co-occurrences affect each voxel.

In tests, a separate computational model was trained for each of the nine research subjects using 58 of the 60 stimulus nouns and their associated activation patterns. The model was then used to predict the activation patterns for the remaining two nouns. For the nine participants, the model had a mean accuracy of 77 percent in matching the predicted activation patterns to the ones observed in the participants’ brains.

The model proved capable of predicting activation patterns even in semantic areas for which it was untrained. In tests, the model was retrained with words from all but two of the 12 semantic categories from which the 60 words were drawn, and then tested with stimulus nouns from the omitted categories. If the categories of vehicles and vegetables were omitted, for instance, the model would be tested with words such as airplane and celery. In these cases, the mean accuracy of the model’s prediction dropped to 70 percent, but was still well above chance (50 percent).

Plans for future work include studying the activation patterns for adjective-noun combinations, prepositional phrases and simple sentences. The team also plans to study how the brain represents abstract nouns and concepts.

Science, 2008; 320 (5880): 1191 DOI: 10.1126/science.1152876

The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

Italian investigators have published a new study on the neurobiologic correlates of the inability to express emotions (alexithymia).

A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation.

A random sample of 300 students was screened for alexithymia using the Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed males and eight females with high alexithymic scores and an age- and gender-matched group with low alexithymic scores were selected. A first (conditioning) magnetic stimulus was delivered to one motor cortex followed by a second (test) stimulus to the opposite hemisphere at different interstimulus intervals for both motor cortices. Motor evoked responses were recorded from the abductor digit minimi muscles.

At the end of the investigation, high alexithymic subjects showed reduced transcallosal inhibition as compared to low alexithymic subjects at interstimulus intervals of 10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer directions.

Results point to functional differences in transcallosal interactions in high alexithymic as compared to low alexithymic subjects, supporting the hypothesis of an interhemispheric transfer deficit in alexithymia.

Psychother Psychosom. 2008;77(3):175-81. Epub 2008 Mar 10.

BACKGROUND: A deficit in interhemispheric transfer was hypothesized in alexithymia more than 30 years ago, following the observation that split-brain patients manifest certain alexithymic characteristics. However, direct evidence of interhemispheric transfer deficit has never been provided. This study investigated the hypothesis of a transcallosal interhemispheric transfer deficit in alexithymia by means of paired-pulse transcranial magnetic stimulation. METHODS: A random sample of 300 students was screened for alexithymia using the Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed males and eight females with high alexithymic scores and an age- and gender-matched group with low alexithymic scores were selected. A first (conditioning) magnetic stimulus was delivered to one motor cortex followed by a second (test) stimulus to the opposite hemisphere at different interstimulus intervals for both motor cortices. Motor evoked responses were recorded from the abductor digit minimi muscles. RESULTS: High alexithymic subjects showed reduced transcallosal inhibition as compared to low alexithymic subjects at interstimulus intervals of 10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer directions. CONCLUSIONS: Results point to functional differences in transcallosal interactions in high alexithymic as compared to low alexithymic subjects, supporting the hypothesis of an interhemispheric transfer deficit in alexithymia. Copyright (c) 2008 S. Karger AG, Basel.

You went to a wedding yesterday. The service was beautiful, the food and drink flowed and there was dancing all night. But people tell you that you are in hospital, that you have been in hospital for weeks, and that you didn’t go to a wedding yesterday at all. The experience of false memories like this following neurological damage is known as confabulation.

The reasons why patients experience false memories such as these has largely remained a mystery. Studies in amnesic patients have associated confabulation with damage to the orbital and ventromedial prefrontal cortices. However, neuroimaging studies have associated memory-control processes which are assumed to underlie confabulation with the right lateral prefrontal cortex.

A new study by Dr Martha Turner and colleagues at University College London offers some clues as to what might be going on. They used a confabulation battery to investigate the occurrence and localisation of confabulation in an unselected series of 38 patients with focal frontal lesions.

Twelve patients with posterior lesions and 50 healthy controls were included for comparison. Significantly higher levels of confabulation were found in the frontal group, confirming previous reports. More detailed grouping according to lesion location within the frontal lobe revealed that patients with orbital, medial and left lateral damage confabulated in response to questions probing personal episodic memory (PEM).

Patients with orbital, medial and right lateral damage confabulated in response to questions probing orientation to time (OT). Performance-led analysis revealed that all patients who produced a total number of confabulations outside the normal range had a lesion affecting either the orbital region or inferior portion of the anterior cingulate.

These data provide striking evidence that the critical deficit for confabulation has its anatomical location in the inferior medial frontal lobe. Performance on tests of memory and executive functioning showed considerable variability. Although a degree of memory impairment does seem necessary, performance on traditional executive tests is less helpful in explaining confabulation.

Martha S Turner, Lisa Cipolotti, Tarek A Yousry, Tim Shallice
Institute of Cognitive Neuroscience, University College London, London, UK.

Confabulation, the pathological production of false memories, occurs following a variety of aetiologies involving the frontal lobes, and is frequently held to be underpinned by combined memory and executive deficits. However, the critical frontal regions and specific cognitive deficits involved are unclear. Studies in amnesic patients have associated confabulation with damage to the orbital and ventromedial prefrontal cortices. However, neuroimaging studies have associated memory-control processes which are assumed to underlie confabulation with the right lateral prefrontal cortex. We used a confabulation battery to investigate the occurrence and localisation of confabulation in an unselected series of 38 patients with focal frontal lesions. Twelve patients with posterior lesions and 50 healthy controls were included for comparison. Significantly higher levels of confabulation were found in the frontal group, confirming previous reports. More detailed grouping according to lesion location within the frontal lobe revealed that patients with orbital, medial and left lateral damage confabulated in response to questions probing personal episodic memory (PEM). Patients with orbital, medial and right lateral damage confabulated in response to questions probing orientation to time (OT). Performance-led analysis revealed that all patients who produced a total number of confabulations outside the normal range had a lesion affecting either the orbital region or inferior portion of the anterior cingulate. These data provide striking evidence that the critical deficit for confabulation has its anatomical location in the inferior medial frontal lobe. Performance on tests of memory and executive functioning showed considerable variability. Although a degree of memory impairment does seem necessary, performance on traditional executive tests is less helpful in explaining confabulation.

Neuroscience researchers at the Duke-NUS Graduate Medical School in Singapore have shown for the first time what happens to the visual perceptions of healthy but sleep-deprived volunteers who fight to stay awake, like people who try to drive through the night.

The scientists found that even after sleep deprivation, people had periods of near-normal brain function in which they could finish tasks quickly. However, this normalcy mixed with periods of slow response and severe drops in visual processing and attention, according to their paper, published in the Journal of Neuroscience on May 21.

“Interestingly, the team found that a sleep-deprived brain can normally process simple visuals, like flashing checkerboards. But the ‘higher visual areas’ — those that are responsible for making sense of what we see — didn’t function well,” said Dr. Michael Chee, lead author and professor at the Neurobehavioral Disorders Program at Duke-NUS. “Herein lies the peril of sleep deprivation.”

The research team, including colleagues at the University of Michigan and University of Pennsylvania, used magnetic resonance imaging to measure blood flow in the brain during speedy normal responses and slow “lapse” responses. The study was funded by grants from the DSO National Laboratories in Singapore, the National Institutes of Health, the National Institute on Drug Abuse, the NASA Commercialization Center, and the Air Force Office of Scientific Research.

Study subjects were asked to identify letters flashing briefly in front of them. They saw either a large H or S, and each was made up of smaller Hs or Ss. Sometimes the large letter matched the smaller letters; sometimes they didn’t. Scientists asked the volunteers to identify either the smaller or the larger letters by pushing one of two buttons.

During slow responses, sleep-deprived volunteers had dramatic decreases in their higher visual cortex activity. At the same time, as expected, their frontal and parietal ‘control regions’ were less able to make their usual corrections.

Scientists also could see brief failures in the control regions during the rare lapses that volunteers had after a normal night’s sleep. However, the failures in visual processing were specific only to lapses that occurred during sleep deprivation.

The scientists theorize that this sputtering along of cognition during sleep deprivation shows the competing effects of trying to stay awake while the brain is shutting things down for sleep. The brain ordinarily becomes less responsive to sensory stimuli during sleep, Chee said.

This study has implications for a whole range of people who have to struggle through night work, from truckers to on-call doctors. “The periods of apparently normal functioning could give a false sense of competency and security when in fact, the brain’s inconsistency could have dire consequences,” Chee said.

“The study task appeared simple, but as we showed in previous work, you can’t effectively memorize or process what you see if your brain isn’t capturing that information,” Chee said. “The next step in our work is to see what we might do to improve things, besides just offering coffee, now that we have a better idea where the weak links in the system are.”

Michael W. L. Chee, Jiat Chow Tan, Hui Zheng, Sarayu Parimal, Daniel H. Weissman, Vitali Zagorodnov, and David F. Dinges
Lapsing during Sleep Deprivation Is Associated with Distributed Changes in Brain Activation
J. Neurosci. 2008 28: 5519-5528; doi:10.1523/JNEUROSCI.0733-08.2008

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night’s sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night’s sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.

Religious leaders have contended for millennia that burning incense is good for the soul. Now, biologists have learned that it is good for our brains too. An international team of scientists, including researchers from Johns Hopkins University and the Hebrew University in Jerusalem, describe how burning frankincense (resin from the Boswellia plant) activates poorly understood ion channels in the brain to alleviate anxiety or depression. This suggests that an entirely new class of depression and anxiety drugs might be right under our noses.

“In spite of information stemming from ancient texts, constituents of Bosweilla had not been investigated for psychoactivity,” said Raphael Mechoulam, one of the research study’s co-authors. “We found that incensole acetate, a Boswellia resin constituent, when tested in mice lowers anxiety and causes antidepressive-like behavior. Apparently, most present day worshipers assume that incense burning has only a symbolic meaning.”

To determine incense’s psychoactive effects, the researchers administered incensole acetate to mice. They found that the compound significantly affected areas in brain areas known to be involved in emotions as well as in nerve circuits that are affected by current anxiety and depression drugs. Specifically, incensole acetate activated a protein called TRPV3, which is present in mammalian brains and also known to play a role in the perception of warmth of the skin. When mice bred without this protein were exposed to incensole acetate, the compound had no effect on their brains.

“Perhaps Marx wasn’t too wrong when he called religion the opium of the people: morphine comes from poppies, cannabinoids from marijuana, and LSD from mushrooms; each of these has been used in one or another religious ceremony.” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Studies of how those psychoactive drugs work have helped us understand modern neurobiology. The discovery of how incensole acetate, purified from frankincense, works on specific targets in the brain should also help us understand diseases of the nervous system. This study also provides a biological explanation for millennia-old spiritual practices that have persisted across time, distance, culture, language, and religion–burning incense really does make you feel warm and tingly all over!”

Arieh Moussaieff, Neta Rimmerman, Tatiana Bregman, Alex Straiker, Christian C. Felder, Shai Shoham, Yoel Kashman, Susan M. Huang, Hyosang Lee, Esther Shohami, Ken Mackie, Michael J. Caterina, J. Michael Walker, Ester Fride, and Raphael Mechoulam

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3-/- mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3-/- mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.