Archive for December 2008
Researchers at Harvard University have discovered that our experience of pain depends on whether we think someone caused the pain intentionally. In their study, participants who believed they were getting an electrical shock from another person on purpose, rather than accidentally, rated the very same shock as more painful. Participants seemed to get used to shocks that were delivered unintentionally, but those given on purpose had a fresh sting every time.
The research, published in the current issue of Psychological Science, was led by Kurt Gray, a graduate student in psychology, along with Daniel Wegner, professor of psychology.
It has long been known that our own mental states can alter the experience of pain, but these findings suggest that our perceptions of the mental states of others can also influence how we feel pain.
“This study shows that even if two harmful events are physically identical, the one delivered with the intention to hurt actually hurts more,” says Gray. “Compare a slap from a friend as she tries to save us from a mosquito versus the same slap from a jilted lover. The first we shrug off instantly, while the second stings our cheek for the rest of the night.”
The study’s authors suggest that intended and unintended harm cause different amounts of pain because they differ in meaning.
“From decoding language to understanding gestures, the mind distills meaning from our social environment,” says Gray. “An intended harm has a very different meaning than an accidental harm.”
The study included 48 participants who were paired up with a partner who could administer to them either an audible tone or an electric shock. In the intentional condition, participants were shocked when their partner chose the shock option. In the unintentional condition, participants were shocked when their partner chose the tone option. Thus, in this condition, they only received a shock when their partner did not intend them to receive one. The computer display ensured that participants both knew their partner’s choice and that a shock would be coming, to ensure the shock was not more surprising in the unintentional condition.
Despite identical shock voltage between conditions, those in the intentional condition rated the shocks as significantly more painful. Furthermore, those in the unintentional condition habituated to the pain, rating them as decreasingly painful, while those in the intentional condition continued to feel the full sting of pain.
Gray suggests that it may be evolutionarily adaptive for this difference in meaning to be represented as different amounts of pain.
“The more something hurts, the more likely we are to take notice and stop whatever is hurting us,” he says. “If it’s an accidental harm, chances are it’s a one-time thing, and there’s no need to do anything about it. If it’s an intentional harm, however, it may be the first of many, so it’s good to take notice and do something about it. It makes sense that our bodies and brains might amplify our experience of pain when we know that the pain could signal threats to our survival.”
These findings speak to how people experience pain and negative life events. If negative events are seen as intended, they may hurt more. This helps to explain why torture is so excruciating – not only are torture techniques themselves exceptionally painful, but it’s the thought that counts—and makes torture hurt more than mere pain.
On the other hand, if negative events are seen as unintended, they may hurt less. This may explain, in part, why people in abusive relationships sometimes continue to stay in them. By rationalizing that an abusive partner did not intend harm, some victims may reduce their experience of pain, which could make them less likely to leave the relationship and escape the abuse.
Psychological Science Volume 19, Issue 12, Date: December 2008, Pages: 1260-1262 DOI 10.1111/j.1467-9280.2008.02208.x
The Sting of Intentional Pain
Kurt Gray, Daniel M. Wegner
All spiritual experiences are based in the brain. That statement is truer than ever before, according to a University of Missouri neuropsychologist. An MU study has data to support a neuropsychological model that proposes spiritual experiences associated with selflessness are related to decreased activity in the right parietal lobe of the brain.
The study is one of the first to use individuals with traumatic brain injury to determine this connection. Researchers say the implication of this connection means people in many disciplines, including peace studies, health care or religion can learn different ways to attain selflessness, to experience transcendence, and to help themselves and others. It sure does not “mean” any such thing, it does at best indicate the possibility, after examining 26 individuals!
Anyway, this study, along with other recent neuroradiological studies of Buddhist meditators and Francescan nuns, seems to suggest that all individuals, regardless of cultural background or religion, experience the same neuropsychological functions during spiritual experiences, such as transcendence. Transcendence, feelings of universal unity and decreased sense of self, is a core tenet of all major religions. Meditation and prayer are the primary vehicles by which such spiritual transcendence is achieved.
“The brain functions in a certain way during spiritual experiences,” said Brick Johnstone, professor of health psychology in the MU School of Health Professions. “We studied people with brain injury and found that people with injuries to the right parietal lobe of the brain reported higher levels of spiritual experiences, such as transcendence.”
This link is important, Johnstone said, because it means selflessness can be learned by decreasing activity in that part of the brain. He suggests this can be done through conscious effort, such as meditation or prayer. People with these selfless spiritual experiences also are more psychologically healthy, especially if they have positive beliefs that there is a God or higher power who loves them, Johnstone said.
“This research also addresses questions regarding the impact of neurologic versus cultural factors on spiritual experience,” Johnstone said. “The ability to connect with things beyond the self, such as transcendent experiences, seems to occur for people who minimize right parietal functioning. This can be attained through cultural practices, such as intense meditation or prayer or because of a brain injury that impairs the functioning of the right parietal lobe. Either way, our study suggests that ‘selflessness’ is a neuropsychological foundation of spiritual experiences.”
“Our research focused on the personal experience of spiritual transcendence and does not in any way minimize the importance of religion or personal beliefs, nor does it suggest that spiritual experience are related only to neuropsychological activity in the brain,” Johnstone said. “It is important to note that individuals experience their God or higher power in many different ways, but that all people from all religions and beliefs appear to experience these connections in a similar way.”
Zygon(r), 2008; 43 (4): 861 DOI: 10.1111/j.1467-9744.2008.00964.x
SUPPORT FOR A NEUROPSYCHOLOGICAL MODEL OF SPIRITUALITY IN PERSONS WITH TRAUMATIC BRAIN INJURY
Brick Johnstone and Bret A. Glass
neuropsychology • spirituality • traumatic brain injury
Recent research suggests that spiritual experiences are related to increased physiological activity of the frontal and temporal lobes and decreased activity of the right parietal lobe. The current study determined if similar relationships exist between self-reported spirituality and neuropsychological abilities associated with those cerebral structures for persons with traumatic brain injury (TBI). Participants included 26 adults with TBI referred for neuropsychological assessment. Measures included the Core Index of Spirituality (INSPIRIT); neuropsychological indices of cerebral structures: temporal lobes (Wechsler Memory Scale-III), right parietal lobe (Judgment of Line Orientation), and frontal lobes (Trail Making Test, Controlled Oral Word Association Test). As hypothesized, spirituality was significantly negatively correlated with a measure of right parietal lobe functioning and positively correlated (nonsignificantly) with measures of left temporal lobe functioning. Contrary to hypotheses, correlations between spirituality and measures of frontal lobe functioning were zero or negative (and nonsignificant). The data support a neuropsychological model that proposes that spiritual experiences are related to decreased activity of the right parietal lobe, which may be associated with decreased awareness of the self (transcendence) and increased activity of the left temporal lobe, which may be associated with the experience of specific religious archetypes (religious figures and symbols).
Even though forgetting is such a common occurrence, scientists have not reached a consensus as to how it happens. One theory is that information simply decays from our memory—we forget things because too much time has passed. Another idea states that forgetfulness occurs when we confuse an item with other items that we have previously encountered (also known as temporal confusability). The illustration below does not contratict either of the two mechanisms.
The Curve of Forgetting describes how we retain or forget information that we learn/memorize. This example is based on memorizing that occurs during a one-hour lecture. (from the University of Waterloo, Counselling Services)
It appears though, that uniqueness of an information compared to its embedding background is more important for its successful memorizing than its iteration over a period of time. (Of course a repeated information within a lecture stands out by its repetitiveness as well, whence the confusion…) Psychologists Nash Unsworth from the University of Georgia, Richard P. Heitz from Vanderbilt University and Nathan A. Parks from the Georgia Institute of Technology investigated the two theories to pinpoint the main cause of forgetfulness over the short term. In their study, the participants were presented with a “Ready” screen (on a computer) for either 1.5 seconds or 60 seconds. Following this, they were presented with a string of three letters and were instructed to remember them for a later test. But, before they were asked to recall the three letters, the volunteers were told to count backwards for various amounts of time (4, 8, 12 or 16 seconds).
The results, reported in Psychological Science, a journal of the Association for Psychological Science, reveal that temporal confusability, and not decay, is important for forgetting over the short term. The volunteers who had to count backwards for the longest amount of time were better able to recall the letters than volunteers who were asked to count backwards for a shorter time period. If decay was the culprit behind forgetting, the group that was asked to count backwards for a longer amount of time would have performed the worst during recall.
The authors conclude that “it is possible to alleviate and even reverse the classic pattern of forgetting by making information distinct, so that it stands out relative to its background”. These findings have very important implications not just for everyday memory use, but also for educational practices and for populations with memory problems, such as the elderly.
Psychological Science, 2008; 19 (11): 1078 DOI: 10.1111/j.1467-9280.2008.02203.x
The Importance of Temporal Distinctiveness for Forgetting Over the Short Term.
Nash Unsworth, Richard P. Heitz, and Nathan A. Parks
ABSTRACT—Rapidly forgetting information once attention is diverted seems to be a ubiquitous phenomenon. The cause of this rapid decline has been debated for decades; some researchers claim that memory traces decay as a function of time out of the focus of attention, whereas others claim that prior memory traces cause confusability by interfering with the current trace. Here we demonstrate that performance after a long delay can be better than performance after a short delay if the temporal confusability between the current item and previous items is reduced. These results provide strong evidence for the importance of temporal confusability, rather than decay, as the cause of forgetting over the short term.
Research conducted by a team in Switzerland suggests that a family of genes involved in regulating the expression of other genes in the brain is responsible for helping us deal with external inputs such as stress. Their results, appearing in the journal Neuron, may also give a clue to why some people are more susceptible to anxiety or depression than others.
The researchers from EPFL and the National Competence Center “Frontiers in Genetics” studied the role of a family of genes known as KRAB-ZFP, which acts like a group of genetic censors, selectively silencing the expression of other genes. These repressors make up about 2% of our genetic material, but little is known about how this “epigenetic” silencing process works, what the long-term consequences are, and even which genes are targeted. (Epigenetics refers to a change in gene expression that is caused by something other than a change in the underlying DNA sequence.)
The researchers bred a strain of mice that lacked in the hippocampus, a part of the forebrain involved in short-term memory and inhibition, a key cofactor used by the KRAB family. The genetically altered mice appeared completely normal until they were placed in a stressful situation. Then they became extremely anxious. Although the normal mice quickly adapted, the altered mice never managed to overcome their stress, and remained anxious and unable to complete simple cognitive tasks. The disruption of the KRAB-mediated regulatory process thus altered the mice’s normal behavioral response to stress.
“The KRAB regulators appeared fairly recently on an evolutionary scale,” notes EPFL professor Didier Trono, lead author on the study, ” and it’s very likely that there is a fair degree of polymorphism between individuals. We postulate that variability in these genes is one factor that may participate in predisposing people to anxiety syndromes or depression. ”
Because epigenetic alterations are often long-lasting and sometimes permanent, one could also interpret them as a way in which an individual’s personal history can have a lasting impact on his or her genetic expression. “It’s a way for a cell to have a sort of memory,” explains Trono.
This work opens promising leads for further exploration, because evidence of epigenetic modification has been observed in animal models of depression, addiction, schizophrenia and neuro-developmental disorders. Some psychoactive drugs like cocaine or anti-psychotics also cause changes in some of the co-factors involved in this genetic regulatory system. With an understanding of the molecular mechanisms involved in epigenetic modulation, it might be possible to develop targeted therapies for those individuals in whom it malfunctions.
Neuron 60(5) pp. 818 – 831 doi:10.1016/j.neuron.2008.09.036
KAP1-Mediated Epigenetic Repression in the Forebrain Modulates Behavioral Vulnerability to Stress
Johan Jakobsson, Maria Isabel Cordero, Reto Bisaz, Anna C. Groner, Volker Busskamp, Jean-Charles Bensadoun, Florence Cammas, Régine Losson, Isabelle M. Mansuy, Carmen Sandi et al.
KAP1 is an essential cofactor of KRAB-zinc finger proteins, a family of vertebrate-specific epigenetic repressors of largely unknown functions encoded in the hundreds by the mouse and human genomes. Here, we report that KAP1 is expressed at high levels and necessary for KRAB-mediated repression in mature neurons of the mouse brain. Mice deleted for KAP1 in the adult forebrain exhibit heightened levels of anxiety-like and exploratory activity and stress-induced alterations in spatial learning and memory. In the hippocampus, a small number of genes are dysregulated, including some imprinted genes. Chromatin analyses of the promoters of two genes markedly upregulated in knockout mice reveal decreased histone 3 K9-trimethylation and increased histone 3 and histone 4 acetylation. We propose a model in which the tethering of KAP1-associated chromatin remodeling factors via KRAB-ZFPs epigenetically controls gene expression in the hippocampus, thereby conditioning responses to behavioral stress.
In a pioneering, interdisciplinary study combining law and neuroscience, researchers at Vanderbilt University peered inside people’s minds to watch how the brain thinks about crime and punishment.
When someone is accused of committing a crime, it is the responsibility of impartial third parties, generally jurors and judges, to determine if that person is guilty and, if so, how much he or she should be punished. But how does one’s brain actually make these decisions? The researchers found that two distinct areas of the brain assess guilt and decide penalty.
This work is the joint effort of Owen Jones, professor of law and of biology, and René Marois, a neuroscientist and associate professor of psychology. Together with neuroscience graduate student Joshua Buckholtz, they scanned the brains of subjects with a highly sensitive technique called functional magnetic resonance imaging or fMRI. Their goal was to see how the brain was activated when a person judged whether or not someone should be punished for a harmful act and how severely the individual should be punished.
During the study, the participant inside the fMRI scanner read scenarios on a computer screen, each describing a person committing an arguably criminal act that varied in harmfulness. With every scenario that appeared, the participant determined how severely to punish the scenario’s protagonist on a scale of 0 (no punishment) to nine (extreme punishment). Sometimes there were extenuating circumstances or background information about why the person acted as he did. Was he coerced? Did he feel threatened? Was he mentally ill?
“We were looking for brain activity reflecting how people reason about the differences in the scenarios,” said Jones.
The researchers found that activity in an analytic part of the brain, known as the right dorsolateral prefrontal cortex, tracked the decision of whether or not a person deserved to be punished but, intriguingly, appeared relatively insensitive to deciding how much to punish. By contrast, the activity in brain regions involved in processing emotions, such as the amygdala, tracked how much subjects decided to punish.
“These results raise the possibility that emotional responses to criminal acts may represent a gauge for assessing deserved punishment,” said Marois.
“There are long-running debates about the proper roles in law of ‘cold’ analysis and ‘hot’ emotion,” said Jones. “Our results suggest that, in normal punishment decisions, the distinct neural circuitries of both processes may be jointly involved, but separately deployed.”
Another intriguing result of the study was that the part of the brain that third-party subjects used to determine guilt in this study was the same brain area that has previously been found to be involved in punishing unfair economic behavior in two-party interactions.
“The convergence of findings between second-party and third-party punishment studies suggests that impartial legal decision-making may not be fundamentally different from the reasoning used in deciding to punish those who have harmed us personally,” said Marois.
Neuron, Volume 60, Issue 5, 738-740, 10 December 2008 Preview
You Shouldn’t Have: Your Brain on Others’ Crimes
Our legal system requires assigning responsibility for crimes and deciding on appropriate punishments. A new fMRI study by Buckholtz etal. in this issue of Neuron reveals that the right dorsolateral prefrontal cortex (rDLPFC) plays a key role in these cognitive processes. This finding sheds light on the neural mechanisms underlying moral judgment from a third-party perspective.
Stop and think for a moment. What do you remember about your breakfast this morning? One part of your brain will recall the smell of coffee brewing, while another will remember your partner’s smile while walking out the door. How does the brain weave together these fragments, and how does it bring them back to conscious life?
Researchers led by Prof. Itzhak Fried, a neurosurgeon at Tel Aviv University’s Sackler Faculty of Medicine, are proving scientifically what scientists have always suspected — that the neurons excited during an experience are the same as those excited when we remember that experience. This finding, reported in the prestigious journal Science in October, gives researchers a clearer picture of how memory recall works and has important implications for understanding dementias such as Alzheimer’s, in which fragments of the memory puzzle seem to disintegrate over time.
A Rare Glimpse Inside Your Brain
“This is a rare opportunity to see how neurons, the basic units of cognition, work during the act of recall,” says Prof. Fried from the University of California Los Angeles (UCLA), where he is also a full professor. “It’s unique because we’re able to look at single cells in the brain when people spontaneously retrieve something from inside their memory without any cue from outside.”
The research was challenging and could only be done on human subjects — other animals lack the ability to verbalize their memories. “Taking a look at individual neurons can only be obtained under special circumstances,” he says. “This is what we’ve managed to achieve.”
Monitoring the subjects’ brain activity as electrodes recorded individual neurons, Prof. Fried and his Israeli colleagues, were effectively able to “see” real human memory recall in action, in real time. This is unprecedented, say his peers, who laud this research as “foundational.”
Where We Lose Our Minds
Prof. Fried located these neurons in the hippocampus of the brain, an important finding in the study. This is the area of the brain affected in Alzheimer’s patients, critical for memory formation and recall. A small part of the brain shaped like a sea horse, the hippocampus stores short-term “episodic” memories: not long-term memories of your childhood, but short-term memories like what you ate for breakfast.
Loss of function in this area of the brain in Alzheimer’s patients explains why they become disoriented in familiar surroundings. “This is the structure in which people lay down new memories and process them,” says Prof. Fried, noting that in his recent study cells were very active in this area. These same cells spring back to life when this new memory is spontaneously recalled in experimental subjects.
From Proust to George Costanza and Homer Simpson?
In the study, Prof. Fried observed the neural activity in the brains of 13 epilepsy patients, as the patients watched clips from TV shows like Seinfeld and The Simpsons. A short while after, the test subjects were asked to describe what they remembered from the video clips. During recall, the exact same neurons that had fired while viewing a clip fired once again while the subject was recalling it. Soon, the researchers were able to predict what clip the subjects would recall just by looking at the neurons that lit up seconds before the recall experience was vocalized.
Prof. Fried, who is associated with Israel’s Ichilov Hospital, plans to continue research that will give science a better understanding of how memories are formed. Prof. Fried says that “the emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind.” Prof. Fried believes that memories are formed by associations, and is curious to discover exactly how these associations are formed and then retrieved from the hippocampus.
Science 3 October 2008: Vol. 322. no. 5898, pp. 96 – 101
Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall
Hagar Gelbard-Sagiv, Roy Mukamel, Michal Harel, Rafael Malach, IItzhak Fried
The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view cinematic episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate for the subjective experience of spontaneous emergence of human recollection.
The virus behind cold sores is a major cause of the insoluble protein plaques found in the brains of Alzheimer’s disease sufferers, University of Manchester researchers have revealed.
They believe the herpes simplex virus is a significant factor in developing the debilitating disease and could be treated by antiviral agents such as acyclovir, which is already used to treat cold sores and other diseases caused by the herpes virus. Another future possibility is vaccination against the virus to prevent the development of the disease in the first place.
Alzheimer’s disease (AD) is characterised by progressive memory loss and severe cognitive impairment. It affects over 20 million people world-wide, and the numbers will rise with increasing longevity. However, despite enormous investment into research on the characteristic abnormalities of AD brain – amyloid plaques and neurofibrillary tangles – the underlying causes are unknown and current treatments are ineffectual.
Professor Ruth Itzhaki and her team at the University’s Faculty of Life Sciences have investigated the role of herpes simplex virus type 1 (HSV1) in AD, publishing their very recent, highly significant findings in the Journal of Pathology.
Most people are infected with this virus, which then remains life-long in the peripheral nervous system, and in 20-40% of those infected it causes cold sores. Evidence of a viral role in AD would point to the use of antiviral agents to stop progression of the disease.
The team discovered that the HSV1 DNA is located very specifically in amyloid plaques: 90% of plaques in Alzheimer’s disease sufferers’ brains contain HSV1 DNA, and most of the viral DNA is located within amyloid plaques. The team had previously shown that HSV1 infection of nerve-type cells induces deposition of the main component, beta amyloid, of amyloid plaques. Together, these findings strongly implicate HSV1 as a major factor in the formation of amyloid deposits and plaques, abnormalities thought by many in the field to be major contributors to Alzheimer’s disease.
The team had discovered much earlier that the virus is present in brains of many elderly people and that in those people with a specific genetic factor, there is a high risk of developing Alzheimer’s disease.
The team’s data strongly suggest that HSV1 has a major role in Alzheimer’s disease and point to the usage of antiviral agents for treating the disease, and in fact in preliminary experiments they have shown that acyclovir reduces the amyloid deposition and reduces also certain other feature of the disease which they have found are caused by HSV1 infection.
Professor Itzhaki explains: “We suggest that HSV1 enters the brain in the elderly as their immune systems decline and then establishes a dormant infection from which it is repeatedly activated by events such as stress, immunosuppression, and various infections.
“The ensuing active HSV1 infection causes severe damage in brain cells, most of which die and then disintegrate, thereby releasing amyloid aggregates which develop into amyloid plaques after other components of dying cells are deposited on them.”
Her colleague Dr Matthew Wozniak adds: “Antiviral agents would inhibit the harmful consequences of HSV1 action; in other words, inhibit a likely major cause of the disease irrespective of the actual damaging processes involved, whereas current treatments at best merely inhibit some of the symptoms of the disease.”
The team now hopes to obtain funding in order to take their work further, enabling them to investigate in detail the effect of antiviral agents on the Alzheimer’s disease-associated changes that occur during HSV1 infection, as well as the nature of the processes and the role of the genetic factor. They very much hope also that clinical trials will be set up to test the effect of antiviral agents on Alzheimer’s disease patients.
The Journal of Pathology, Volume 217, Issue 1 , Pages131 – 138 DOI: 10.1002/path.2449
Herpes simplex virus type I DNA is located within Alzheimer’s disease amyloid plaques.
MA Wozniak, AP Mee and RF Itzhaki
The brains of Alzheimer’s disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer’s disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-4), and that -amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer’s disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80% of plaques contained herpes simplex virus type 1 DNA but only 24% of the viral DNA was plaque-associated (p < 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of -amyloid (A), so that less of the viral DNA is seen to be associated with A in the brain. Our present data, together with our finding of A accumulation in herpes simplex virus type 1-infected cells and mouse brain, suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer’s disease. They point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.