Archive for December 2007
Humour appears to develop from aggression caused by male hormones, according to a “study” published in the Christmas issue of the British Medical Journal. This respectable periodical has lately lost it’s taste for logic or has developed a taste for Christmas-hoaxes. The humorous rather than scientific report is funny reading and a beautiful demonstration of logical fallacies.
Professor Sam Shuster observed for one year how people reacted to him as he unicycled through the streets of Newcastle upon Tyne. After some 400 anecdotical observations he concluded that he received stereotypical and predictable responses and that they must be indicative of an underlying biological phenomenon – nice chain of logically faulty conclusions (non sequitur). The results he published are amusing anyway.
Over 90% of people responded physically, for example with an exaggerated stare or a wave. Almost half responded verbally — more men than women. Here, says Professor Shuster, the sex difference was striking. 95% of adult women were praising, encouraging or showed concern. There were very few comic or snide remarks. In contrast, only 25% of adult men responded as did the women, for example, by praise or encouragement; instead 75% attempted comedy, often snide or combative as an intended put-down.
Equally striking, he says, was the repetitive and predictable nature of the comments from men; two thirds of their ‘comic’ responses referred to the number of wheels – “Lost your wheel?”, for example.
Professor Shuster also noticed the male response differed markedly with age, moving from curiosity in childhood (years 5-12) — the same reaction as young girls, – to physical and verbal aggression in boys aged 11-13 who often tried to get him to fall off the unicycle.
Responses became more verbal during the later teens, turning into disparaging ‘jokes’ or mocking songs. This then evolved into adult male humour — characterized by repetitive, humorous verbal put-downs concealing a latent aggression. Young men in cars were particularly aggressive. Professor Shuster notes that this is the age when men are at the peak of their virility. The ‘jokes’ were lost with age as older men responded more neutrally and amicably with few attempts at a jovial put-down.
The female response by contrast, was subdued during puberty and late teens — normally either apparent indifference or minimal approval. It then evolved into the laudatory and concerned adult female response.
The idea that unicycling is intrinsically funny does not explain the findings, says Professor Shuster, particularly the repetitiveness, evolution and sex differences. Genetics may explain the sex difference but not the waxing and waning of the male response. He says the simplest explanation for this change is the effect of male hormones such as testosterone, known collectively as androgens, which induce virility in men. What looks like elegant Ockham’s razor, means in fact begging the question – the easiest explanation for all of Professor Shusters observations is, that they are contingent, and anything beyond belongs into the realm of statistics of small numbers.
His further observations that initial aggressive intent seems to become channeled into a verbal response which pushes it into a contrived, but more subtle and sophisticated joke, so that the aggression would be hidden by wit, can be found, together with more sound considerations in Freud’s „Der Witz und seine Beziehung zum Unbewussten“ (1905).
BMJ 2007;335:1320-1322 (22 December), doi:10.1136/bmj.39414.552060.BE
Sex, aggression, and humour: responses to unicycling
Sam Shuster, honorary consultant, emeritus professor of dermatology
1 Department of Dermatology, Norfolk and Norwich University Hospital, Norwich NR4 7UY
Sam Shuster compares men and women’s responses to the sight of a unicyclist
After retiring from a busy university department in Newcastle upon Tyne, and with the time and the need for more than the usual consultancies, I was able follow some of my more extreme inclinations. As a cyclist, I had occasionally thought of using more or fewer wheels, but it was only when choosing a grandson’s gift that I got seriously lost in contemplation of a gleaming chrome unicycle. My wife said “buy the bloody” thing, which I did on the whim of the moment. After months of practice at home, I graduated to back streets, a small paved park, and finally town roads. I couldn’t avoid being noticed; in turn, I couldn’t avoid observing the form that notice took. Because at the time there were no other unicyclists in the area, such sightings would have been exceptional, yet I soon found that the responses to them were stereotyped and predictable. I realised that this indicated an underlying biological phenomenon and set about its study.
Using new approaches, an interdisciplinary team of scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City has gained a view of activity in key brain areas associated with a core difficulty in patients with borderline personality disorder—shedding new light on this serious psychiatric condition.
“It’s early days yet, but the work is pinpointing functional differences in the neurobiology of healthy people versus individuals with the disorder as they attempt to control their behavior in a negative emotional context. Such initial insights can help provide a foundation for better, more targeted therapies down the line,” explains lead researcher Dr. David A. Silbersweig, the Stephen P. Tobin and Dr. Arnold M. Cooper Professor of Psychiatry and Professor of Neurology at Weill Cornell Medical College, and attending psychiatrist and neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Borderline personality disorder is a devastating mental illness that causes untold disruption of patients’ lives and relationships. Nevertheless, its underlying biology is not very well understood. Hallmarks of the illness include impulsivity, emotional instability, interpersonal difficulties, and a preponderance of negative emotions such as anger—all of which may encourage or be associated with substance abuse, self-destructive behaviors and even suicide.
“In this study, our collaborative team looked specifically at the nexus between negative emotions and impulsivity—the tendency of people with borderline personality disorder to ‘act out’ destructively in the presence of anger,” Dr. Silbersweig explains. “Other studies have looked at either negative emotional states or this type of behavioral disinhibition. The two are closely connected, and we wanted to find out why. We therefore focused our experiments on the interaction between negative emotional states and behavioral inhibition.”
Advanced brain-scanning technologies developed by the research team made it possible to detect the brain areas of interest with greater sensitivity.
“Previous work by our group and others had suggested that an area at the base of the brain within the ventromedial prefrontal cortex was key to people’s ability to restrain behaviors in the presence of emotion,” Dr. Silbersweig explains.
Unfortunately, tracking activity in this brain region has been extremely difficult using functional MRI (fMRI). “Due to its particular location, you get a lot of signal loss,” the researcher explains.
However, the Weill Cornell team used a special fMRI activation probe that they developed to eliminate much of that interference. This paved the way for the study, which included 16 patients with borderline personality disorder and 14 healthy controls.
The team also used a tailored fMRI neuropsychological approach to observe activity in the subjects’ ventromedial prefrontal cortex as they performed what behavioral neuroscience researchers call “go/no go” tests.
These rapid-fire tests require participants to press or withhold from pressing a button whenever they receive particular visual cues. In a twist from the usual approach, the performance of the task with negative words (related to borderline psychology) was contrasted with the performance of the task when using neutral words, to reveal how negative emotions affect the participants’ ability to perform the task.
As expected, negative emotional words caused participants with borderline personality disorder to have more difficulty with the task at hand and act more impulsively—ignoring visual cues to stop as they repeatedly pressed the button.
But what was really interesting was what showed up on fMRI.
“We confirmed that discrete parts of the ventromedial prefrontal cortex—the subgenual anterior cingulate cortex and the medial orbitofrontal cortex areas—were relatively less active in patients versus controls,” Dr. Silbersweig says. “These areas are thought to be key to facilitating behavioral inhibition under emotional circumstances, so if they are underperforming that could contribute to the disinhibition one so often sees with borderline personality disorder.”
At the same time, the research team observed heightened levels of activation during the tests in other areas of the patients’ brains, including the amygdala, a locus for emotions such as anger and fear, and some of the brain’s other limbic regions, which are linked to emotional processing.
“In the frontal region and the amygdala, the degree to which the brain aberrations occurred was closely correlated to the degree with which patients with borderline personality disorder had clinical difficulty controlling their behavior, or had difficulty with negative emotion, respectively,” Dr. Silbersweig notes.
The study sheds light not only on borderline personality disorder, but on the mechanisms healthy individuals rely on to curb their tempers in the face of strong emotion.
Still, patients struggling with borderline personality disorder stand to benefit most from this groundbreaking research. An accompanying journal commentary labels the study “rigorous” and “systematic,” and one of the first to validate with neuroimaging what scientists had only been able to guess at before.
“The more that this type of work gets done, the more people will understand that mental illness is not the patient’s fault—that there are circuits in the brain that control these functions in humans and that these disorders are tied to fundamental disruptions in these circuits,” Dr. Silbersweig says. “Our hope is that such insights will help erode the stigma surrounding psychiatric illness.”
The research could even help lead to better treatment.
As pointed out in the commentary, the research may help explain how specific biological or psychological therapies could ease symptoms of borderline personality disorder for some patients, by addressing the underlying biology of impulsivity in the context of overwhelming negative emotion. The more scientists understand the neurological aberrations that give rise to the disorder, the greater the hope for new, highly targeted drugs or other therapeutic interventions.
“Going forward, we plan to test hypotheses about changes in these brain regions associated with various types of treatment,” Dr. Silberswieg says. “Such work by ourselves and others could help confirm these initial findings and point the way to better therapies.”
Am J Psychiatry. 2007 Dec;164(12):1832-41.Click here to read Links
Failure of frontolimbic inhibitory function in the context of negative emotion in borderline personality disorder.
Silbersweig D, Clarkin JF, Goldstein M, Kernberg OF, Tuescher O, Levy KN, Brendel G, Pan H, Beutel M, Pavony MT, Epstein J, Lenzenweger MF, Thomas KM, Posner MI, Stern E.
Department of Psychiatry, Box 140, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. dasilber@med.
OBJECTIVE: The authors sought to test the hypothesis that in patients with borderline personality disorder, the ventromedial prefrontal cortex and associated regions would not be activated during a task requiring motor inhibition in the setting of negative emotion. Such a finding would provide a plausible neural basis for the difficulty borderline patients have in modulating their behavior during negative emotional states and a potential marker for treatment interventions. METHOD: A specifically designed functional magnetic resonance imaging (fMRI) activation probe was used, with statistical parametric mapping analyses, to test hypotheses concerning decreased prefrontal inhibitory function in the context of negative emotion in patients with borderline personality disorder (N=16) and healthy comparison subjects (N=14). 3-T fMRI scanning was used to study brain activity while participants performed an emotional linguistic go/no-go task. RESULTS: Analyses confirmed that under conditions associated with the interaction of behavioral inhibition and negative emotion, borderline patients showed relatively decreased ventromedial prefrontal activity (including medial orbitofrontal and subgenual anterior cingulate) compared with healthy subjects. In borderline patients, under conditions of behavioral inhibition in the context of negative emotion, decreasing ventromedial prefrontal and increasing extended amygdalar-ventral striatal activity correlated highly with measures of decreased constraint and increased negative emotion, respectively. CONCLUSIONS: These findings suggest specific frontolimbic neural substrates associated with core clinical features of emotional and behavioral dyscontrol in borderline personality disorder.
Cannabinoids may suppress tumor invasion in highly invasive cancers, according to a study published online December 25 in the Journal of the National Cancer Institute.
Schematic representation of TIMP-1 structure. TIMP1 contains 12 cysteine residues which form six loop structures through disulfide bonds. The N-terminus of TIMPs 1-4 binds to the catalytic domain of most activated MMPs and inhibits function. The C-terminus of TIMP1 and TIMP2 binds to the hemopexin domain of proMMP2 and proMMP9, respectively; this binding regulates MMP function.
Cannabinoids, the active components in marijuana, are used to reduce the side effects of cancer treatment, such as pain, weight loss, and vomiting, but there is increasing evidence that they may also inhibit tumor cell growth. However, the cellular mechanisms behind this are unknown.
Robert Ramer, Ph.D., and Burkhard Hinz, Ph.D., of the University of Rostock in Germany investigated whether and by what mechanism cannabinoids inhibit tumor cell invasion.
Cannabinoids did suppress tumor cell invasion and stimulated the expression of TIMP-1, an inhibitor of a group of enzymes that are involved in tumor cell invasion.
“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids. This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials,” the authors write.
J Natl Cancer Inst. 2007 Dec 25
Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1.
Ramer R, Hinz B.
Affiliation of authors: Institute of Toxicology and Pharmacology, University of Rostock, Rostock, Germany.
Background Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Although the antiproliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion. Methods Matrigel-coated and uncoated Boyden chambers were used to quantify invasiveness and migration, respectively, of human cervical cancer (HeLa) cells that had been treated with cannabinoids (the stable anandamide analog R(+)-methanandamide [MA] and the phytocannabinoid Delta(9)-tetrahydrocannabinol [THC]) in the presence or absence of antagonists of the CB(1) or CB(2) cannabinoid receptors or of transient receptor potential vanilloid 1 (TRPV1) or inhibitors of p38 or p42/44 mitogen-activated protein kinase (MAPK) pathways. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting were used to assess the influence of cannabinoids on the expression of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs). The role of TIMP-1 in the anti-invasive action of cannabinoids was analyzed by transfecting HeLa, human cervical carcinoma (C33A), or human lung carcinoma cells (A549) cells with siRNA targeting TIMP-1. All statistical tests were two-sided. Results Without modifying migration, MA and THC caused a time- and concentration-dependent suppression of HeLa cell invasion through Matrigel that was accompanied by increased expression of TIMP-1. At the lowest concentrations tested, MA (0.1 muM) and THC (0.01 muM) led to a decrease in invasion (normalized to that observed with vehicle-treated cells) of 61.5% (95% CI = 38.7% to 84.3%, P < .001) and 68.1% (95% CI = 31.5% to 104.8%, P = .0039), respectively. The stimulation of TIMP-1 expression and suppression of cell invasion were reversed by pretreatment of cells with antagonists to CB(1) or CB(2) receptors, with inhibitors of MAPKs, or, in the case of MA, with an antagonist to TRPV1. Knockdown of cannabinoid-induced TIMP-1 expression by siRNA led to a reversal of the cannabinoid-elicited decrease in tumor cell invasiveness in HeLa, A549, and C33A cells. Conclusion Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.
A new fMRI study of twins indicates that the genetic foundation for the brain’s ability to recognize faces and places is much stronger than for other objects, such as words. The authors claim, somewhat pompously, to have digged into the problem of “Nature versus nurture in ventral visual cortex…”. As can be seen in other places, the problem is none. No human brain activity is going to be either of the two, exclusively. Nonetheless, the results are a hint pointing towards the role of genetics in assigning these functions to specific regions of the brain.
“We are social animals who have specialized circuitry for faces and places,” says Arthur W. Toga, PhD, director of the Laboratory of NeuroImaging at UCLA School of Medicine. “Some people are better at recognizing faces and places, and this study provides evidence that it is partially determined by genetics.”Using a functional magnetic resonance imaging (fMRI) scanner, Thad Polk, PhD, Joonkoo Park, and Mason Smith of the University of Michigan, along with Denise Park, PhD, at the University of Illinois at Urbana-Champaign, measured activity in the visual cortex of 24 sets of fraternal and identical twins. The twins watched several series of images: sets of people’s faces, houses, letters strung together, and chairs, as well as scrambled images that served as a baseline measurement.Previous research had identified distinct regions in the visual cortex where different categories of information are processed, a sort of division of labor in the brain that handles information about people, for example, independently of that related to cars.
Polk’s analysis of brain activity patterns from the twins suggests how the organization of these independent regions is shaped. By showing greater similarity in the brain activity of identical twins than their fraternal counterparts when processing faces and places, the results indicate a genetic basis for these functions. Activity in response to words, Polk suggests, may be shaped to a greater degree by one’s experiences and environment.
“Face and place recognition are older than reading on an evolutionary scale, they are shared with other species, and they provide a clearer adaptive advantage,” says Polk. “It is therefore plausible that genetics would shape the cortical response to faces and places, but not orthographic stimuli.”
Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA. email@example.com
Using functional magnetic resonance imaging, we estimated neural activity in twins to study genetic influences on the cortical response to categories of visual stimuli (faces, places, and pseudowords) that are known to elicit distinct patterns of activity in ventral visual cortex. The neural activity patterns in monozygotic twins were significantly more similar than in dizygotic twins for the face and place stimuli, but there was no effect of zygosity for pseudowords (or chairs, a control category). These results demonstrate that genetics play a significant role in determining the cortical response to faces and places, but play a significantly smaller role (if any) in the response to orthographic stimuli.
Researchers from the Center for the Neural Basis of Cognition (CNBC), a joint project of Carnegie Mellon University and the University of Pittsburgh, have for the first time described a mechanism called “dynamic connectivity,” in which neuronal circuits are rewired “on the fly” allowing stimuli to be more keenly sensed.
“If you think of the brain like a computer, then the connections between neurons are like the software that the brain is running. Our work shows that this biological software is changed rapidly as a function of the kind of input that the system receives,” said Nathan Urban, associate professor of biological sciences at Carnegie Mellon.
When a stimulus such as an odor is encountered, many neurons start to fire. When many neurons fire at the same time, the signals can be difficult for the brain to interpret. During lateral inhibition, the stimulated neurons send “cease-fire” messages to the neighboring neurons, reducing the noise and making it easier to precisely identify a stimulus. This process also facilitates accurate recognition of stimuli in many sensory areas of the brain.
In this project, Urban and colleagues specifically examine the process of lateral inhibition in an area of the brain called the olfactory bulb, which is responsible for processing scents. Until now, scientists thought that the connections made by the neurons in the olfactory bulb were dictated by anatomy and could only change slowly.
However, in this current study, Urban and colleagues found that the connections are, in fact, not set but rather able to change dynamically in response to specific patterns of stimuli. In their experiments, they found that when excitatory neurons in the olfactory bulb fire in a correlated fashion, this determines how they are functionally connected.
The researchers showed that dynamic connectivity allows lateral inhibition to be enhanced when a large number of neurons initially respond to a stimulus, filtering out noise from other neurons. By filtering out the noise, the stimulus can be more clearly recognized and separated from other similar stimuli.
“This mechanism helps to explain why you can walk into a room and recognize a smell that seems to be floral. As you continue to smell the odor, you begin to recognize that the scent is indeed flowers and even more specifically is the scent of roses,” Urban said. “By understanding how the brain does this, we can then apply this mechanism to other problems faced by the brain.”
Researchers converted this mechanism into an algorithm and used computer modeling to further show that dynamic connectivity makes it easier to identify and discriminate between stimuli by enhancing the contrast, or sharpness, of the stimuli, independent of the spatial patterns of the active neurons. This algorithm allows researchers to show the applicability of the mechanism in other areas of the brain where similar inhibitory connections are widespread. For example, the researchers applied the algorithm to a blurry picture and the picture appeared refined and in sharper contrast (see image).
Nature Neuroscience Published online: 16 December 2007 | doi:10.1038/nn2030
Activity-dependent gating of lateral inhibition in the mouse olfactory bulb
Lateral inhibition is a circuit motif found throughout the nervous system that often generates contrast enhancement and center-surround receptive fields. We investigated the functional properties of the circuits mediating lateral inhibition between olfactory bulb principal neurons (mitral cells) in vitro. We found that the lateral inhibition received by mitral cells is gated by postsynaptic firing, such that a minimum threshold of postsynaptic activity is required before effective lateral inhibition is recruited. This dynamic regulation allows the strength of lateral inhibition to be enhanced between cells with correlated activity. Simulations show that this regulation of lateral inhibition causes decorrelation of mitral cell activity that is evoked by similar stimuli, even when stimuli have no clear spatial structure. These results show that this previously unknown mechanism for specifying lateral inhibitory connections allows functional inhibitory connectivity to be dynamically remapped to relevant populations of neurons.
- Center for Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, Pennsylvania 15260, USA.
- Center for the Neural Basis of Cognition, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
- Department of Biology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
Knowledge is life with wings.
(Extract from one of Gibran’s letters dated 15th November 1917)
“People change after potentially tragic events; it is unrealistic to think that you can go right back to the way you were before the event,” King said. “It might be best to try and make meaning out of what has happen and start a new life that is tied to what you have learned from the change. Being happy is not about forgetting the past, but forming a life that is founded on what you had before, or who you used to be.”
Department of Psychological Sciences, University of Missouri-Columbia, MO 65201, USA. firstname.lastname@example.org
Although lost opportunities and mistaken expectations are unpleasant to think and talk about, these experiences may have a role to play in personality development. Drawing on research using narratives of lost possible selves, the authors review the relations of regrettable experiences to 2 important and independent aspects of maturity, happiness and complexity. Thinking about a lost possible self is related to concurrent regrets, distress, and lowered well-being; however, elaborating on a lost possible self is related, concurrently, to complexity and predicts complexity, prospectively, over time. In this article, the authors describe the role that regrettable experiences have in promoting both happiness and complexity. Finally, expanding on previous work, the authors examine potential affordances of happy maturity and suggest psychological capacities that may promote happy maturity. Copyright 2007 APA, all rights reserved.