Drug craving? - Just zap your insula!

An important factor that contributes to drug-seeking in addicted individuals is the negative feelings that result from abstinence. Such mood states are monitored by the interoceptive sensory system, and particularly by a brain area called the insular cortex, known to process emotional information. Thus this abstract from Contreras et al. is of interest:

Addiction profoundly alters motivational circuits so that drugs become powerful reinforcers of behavior. The interoceptive system continuously updates homeostatic and emotional information that are important elements in motivational decisions. We tested the idea that interoceptive information is essential in drug craving and in the behavioral signs of malaise. We inactivated the primary interoceptive cortex in amphetamine-experienced rats, which prevented the urge to seek amphetamine in a place preference task. Interoceptive insula inactivation also blunted the signs of malaise induced by acute lithium administration. Drug-seeking and malaise both induced Fos expression, a marker of neuronal activation, in the insula. We conclude that the insular cortex is a key structure in the perception of bodily needs that provides direction to motivated behaviors.

The therapeutic intervention was an injection of 2% lidocaine (a sodium channel blocker to inhibit nerve activity) into the left and right insula to cause a transient shutdown of insular nerve activity (injecting adjacent cortex was not effective). Although this is a sledgehammer approach with possible dire side effects, it suggests that therapeutic interventions in the insula may help to alleviate drug cravings, .

Music and Dancing

Daniel Levitin has offered this brief essay in the New York Times Op-Ed section.

Less SAD with more sun and serotonin

Welberg offers a summary and review of work by Willeit et al. on the role of serotonin, and a serotonin transporter, in seasonal affective disorder. Here is an portion of the review:

Short, dark winter days put most of us in a gloomy mood, but in people with seasonal affective disorder (SAD), they can cause severe clinical depression. Fortunately, this depression can be treated with bright-light therapy (BLT), and it disappears altogether in summer. Willeit et al. now show that these changes in mood are associated with alterations in the efficiency of the serotonin (5-hydroxytryptamine) transporter (5-HTT) in the patients' blood platelets.

One theory of depression posits that impaired functioning of monoamine neurotransmitters, such as serotonin, causes the disorder, but it is unknown how this impairment might arise. Serotonin levels in the synapse are controlled by the 5-HTT, and Willeit and colleagues therefore investigated whether alterations in 5-HTT functioning might underlie depression in SAD.

The authors compared people with SAD with healthy volunteers, and assessed 5-HTT functioning in winter, after 4 weeks of BLT and in summer. They did this by measuring 5-HTT-mediated inward and outward transport in blood platelets (which are easily obtainable). In winter, both inward transport rate and outward transport were enhanced in the platelets of SAD patients compared with healthy controls. Importantly, these differences in platelet 5-HTT functioning disappeared after 4 weeks of BLT and were absent in summer. The number of 5-HTTs and their affinity for serotonin did not change with BLT or with the seasons, indicating that the increased 5-HTT inward transport that was found in SAD patients was due to increased efficiency of the transporter.

The authors also assessed the patients' depression levels at the three time points, using a structured interview. They found that post-treatment, both inward transport rate and outward transport correlated with depression scores in SAD patients. Moreover, patients whose depression did not decrease after treatment did not show a change in 5-HTT-mediated outward transport after treatment.

Are we having fun?

This is an engaging bit of fluff, be happy! (if the Strauss waltz repeated in a loop doesn't drive you crazy.)

Short-term meditation training improves attention and self-regulation

An interesting study from Tang et al. showing that even short term meditation training can influence attention and self-regulation. The integrative meditation method used:

...stresses no effort to control thoughts, but instead a state of restful alertness that allows a high degree of awareness of body, breathing, and external instructions from a compact disc. It stresses a balanced state of relaxation while focusing attention. Thought control is achieved gradually through posture and relaxation, body–mind harmony, and balance with the help of the coach rather than by making the trainee attempt an internal struggle to control thoughts in accordance with instruction.

Their abstract:

Recent studies suggest that months to years of intensive and systematic meditation training can improve attention. However, the lengthy training required has made it difficult to use random assignment of participants to conditions to confirm these findings. This article shows that a group randomly assigned to 5 days of meditation practice with the integrative body–mind training method shows significantly better attention and control of stress than a similarly chosen control group given relaxation training. The training method comes from traditional Chinese medicine and incorporates aspects of other meditation and mindfulness training. Compared with the control group, the experimental group of 40 undergraduate Chinese students given 5 days of 20-min integrative training showed greater improvement in conflict scores on the Attention Network Test, lower anxiety, depression, anger, and fatigue, and higher vigor on the Profile of Mood States scale, a significant decrease in stress-related cortisol, and an increase in immunoreactivity. These results provide a convenient method for studying the influence of meditation training by using experimental and control methods similar to those used to test drugs or other interventions.

Another window into the minds of chimps and humans

Rilling et al. compare resting-state brain activity in humans and chimpanzees:

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individual's perspective. Here we use [18F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing.

Our Brains on Music, and Musicophilia

Steven Pinker has called music useless, with no adaptive value. Oliver Sacks and Daniel Levitin beg to differ. I'm currently reading and enjoying Oliver Sacks' new book: Musicophilia: Tales of Music and the Brain. I'm linking you to a review of this book by Laura Garwin in the current issue of Nature that notes that our brains seem to be finely tuned to music, and asks of what use are our musical powers and passions? She also reviews Levitin's "This is Your Brain on Music: Understanding a Human Obsession." I also thoroughly enjoyed reading this book this past spring, it has a very accessible introduction of the fundamentals of music structure and brain mechanisms associated with music processing.

The hash realities

Murray et al. offer an interesting history and analysis of Cannabis use, with several interesting graphics (PDF here):

Cannabis has been known for at least 4,000 years to have profound effects on the mind — effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use.

A Consciousness Debate

Christof Koch and Susan Greenfield offer a written version of their Oxford University Debate in the summer of 2006 in the Oct. 2007 issue of Scientific American. While they make a point of contrasting their models of the neuronal correlates of consciousness, I think a blending of the two may most closely approach the real situation.

What happens in your brain when you see a dog, hear a voice, suddenly feel sad or have any other subjective experience?

KOCH'S MODEL
A coalition of pyramidal neurons linking the back and front of the cortex fires in a unique way. Different coalitions activate to represent different stimuli from the senses (left). In a mouse cortex (right) these pyramidal cells (green) lie in brain layer 5, surrounded by nonneuronal cells (blue).


GREENFIELD'S MODEL
Neurons across the brain fire in synchrony (green) and prevail until a second stimulus prompts a different assembly to arise (orange). Various assemblies coalesce and disband moment to moment, while incorporating feedback from the body. In a rat brain (bottom), an assembly in the cortex forms (a, b), peaks (c), then decays (d) within 0.35 second after the thalamus is electrically stimulated.

Christof Koch is professor of cognitive and behavioral biology at the California Institute of Technology, where he teaches and has conducted research on the neuronal basis of visual attention and consciousness for more than two decades.

Susan Greenfield is professor of pharmacology at the University of Oxford, director of the Royal Institution of Great Britain and member of the British Parliament's House of Lords. Her research focuses on novel brain mechanisms, including those underlying neurodegenerative diseases.

A new consiousness and philosophy of mind bibliography

David Chalmers and David Bourget are offering a more extensive online service, outlined in this message from ASSC (Assoc. for Sci.Stud. Cons.):

We are pleased to announce the launch of MindPapers, a new website
with a bibliography covering around 18000 published papers and online
papers in the philosophy of mind and the science of consciousness.
This site grew out of a combination of David Chalmers' bibliography in
philosophy of mind and his page of online papers on consciousness, but
it is much larger and has many new capacities, programmed by David
Bourget. The site address is:

http://consc.net/mindpapers/

There is also a separate front end for "Online Papers on
Consciousness". Where MindPapers now combines both offline published
papers and online papers from free and commercial sites, Online Papers
on Consciousness is devoted to free online papers (currently around
4700). It is based on the same database as MindPapers, but is
organized in a way to emphasize issues concerning consciousness and
cognitive science rather than the philosophy of mind. The address is

http://consc.net/online/

The MindPapers database contains 2773 papers on the philosophy of
consciousness (under 59 topics and subtopics) and 3917 papers on the
science of consciousness (under 71 topics and subtopics), as well as
thousands of papers on such related topics as perception,
intentionality, the philosophy of AI, and the philosophy of cognitive
science.

Capacities include (i) links and citation information throughout, (ii)
flexible navigation, display, and search options, (iii) the ability to
submit and edit entries, (iv) the capacity for automated off-campus
proxy access to commercial sites, and (v) a wealth of statistical
information.

We encourage everyone to try these sites to submit any relevant
material that we are missing (for a start, try searching on your own
name). There are tools on the site for submitting entries, as well as
for correcting entries and notifying us of any bugs and suggestions.

--David Chalmers and David Bourget
chalmers@anu.edu.au; david.bourget@anu.edu.au

Sleep deprivation diminishes recall of neutral and positive, but not of negative, events.

We remember emotional events, particularly negative ones, better than neutral events. Sterpenich et al. show that while consolidation of neutral and posititive memories is diminished by sleep deprivation, recall of negative events is less compromised. They show that after sleep deprivation, recollection of negative, potentially dangerous, memories recruits an alternate amygdalo-cortical network, which would keep track of emotional information despite sleep deprivation. Here is their description of the work:

Declarative memories, which can be consciously and verbally retrieved, are initially critically dependent on the hippocampus. However, reliable retrieval of long-term memory depends on a process of consolidation, which partly occurs during sleep, when memories are thought to be progressively transferred to long-term cortical stores. Because people tend to remember emotional memories better than neutral ones, we wondered whether the emotional significance of a memory would enhance its consolidation in a sleep-dependent manner. During a first session, participants viewed pictures with neutral and emotional content without realizing that their memory of the pictures and their content would be tested later (called incidental encoding). Three days later, during a functional MRI scanning session, subjects indicated whether they recognized previously viewed and new pictures. Half of the subjects were totally sleep deprived during the first post-encoding night, but all subjects slept as usual during the second and third post-encoding nights. We show here that the recollection of emotional stimuli elicited larger responses in the hippocampus and various cortical areas in the well-rested group than in the sleep-deprived group, suggesting that emotional significance boosts memory consolidation of the information during sleep. Interestingly, in sleep-deprived subjects, recollection of negative items recruited another network including the amygdala, as if an alternate consolidation process allowed them to keep track of negative, potentially dangerous, information despite the cognitive aftermath of sleep deprivation.

Biology and Health Inequality

PLoS Biology has ventured beyond its usual fare to publish several articles focusing on poverty, human development, and the environment. This article is from Eric Brunner. He points out several studies that demonstrate a direct psychosocial pathway to disease. It's precis: "Intriguing parallels between civil servant and nonhuman primate hierarchies suggest that highly stratified societies foster health inequalities. Determining how social differences translate into chronic disease remains a challenge, but neuroendocrine pathways appear to play a role."

Silent Minds

I want to point you to an excellent article by Jerome Groopman, with the title of this post, that appeared in a recent New Yorker Magazine. It describes recent work showing that brain imaging of some vegetative patients reveals responses to faces, and other visual and auditory inputs, that are indistinguishable from those of normal subjects (note: there are approximately 35,000 Americans in a vegetative state and another 280,000 in a minimally conscious state). Responses during various mental tasks, such as resolving ambiguous sentences or imagining playing a tennis game, can also be normal. This shows that an assumption held by doctors for decades - that vegetative patients lack capacity for conscious thought - is incorrect. Other vegetative patients (such as Terri Schiavo), in contrast, can show almost no cortical activity.

This all suggests a better medical definition of consciousness is required - such as the ability to report to ourselves or others the content of the representations in our brains, to sustain these representations over time and broadcast them broadly within the brain.

Evolution - with feeling....

A recent issue of American Scientist has a review by Robert Pennock of two books that attempt to show that a mechanistic Darwinian view of the world does not have to lead to a nihilistic ennui, but rather can satisfy our need to feel richness, purpose, and meaning.

With the familiar references to the "uncaring" Darwinian struggle, and the "mechanical" and "pitiless" action of natural selection, evolutionary biology has long been the obvious whipping boy for those who are uncomfortable with scientific naturalism. It is not just fundamentalist religious beliefs that motivate creationists' attacks on evolution; they are also driven by a deep existential angst—a fear that evolution renders the world pointless, emptying it of purpose, meaning and morality.

In "Darwin Loves You:Natural Selection and the Re-enchantment of the World" George Levine argues that evolution

if properly portrayed, is not only perfectly compatible with meaningfulness but provides a new basis for it...He makes the important point that at the same time that evolution pulls the rug out from under anthropocentrism (which is not only a smug but ultimately a dangerous attitude), it provides a foundation for a justifiable form of anthropomorphism. Darwin showed that humans are not the apex of creation but are one with the rest of the biological world, related to all living things through our common ancestors. This discovery allows us to find common ground with other animals without denigrating our humanness, Levine argues, permitting us to legitimately attribute human characteristics (albeit in simpler or incipient forms) to them. This provides an avenue to the re-enchantment of the world, for it shows we are not wrong to find in it a recognizably human notion of meaningfulness. It is wrong to see nature as cold and unfeeling; for those who understand evolutionary processes and relationships, the biological world becomes a warm and caring network of mutual interactions that are suffused with meaning. Levine is a romantic, but not a naive one; he does not close his eyes to those aspects of nature that are "red in tooth and claw," but shows how these need not negate the positive vision.

In "Evolution for Everyone: How Darwin's Theory Can Change the Way We Think about Our Lives" David Sloan Wilson, in the service of finding harmony between evolution and religion:

...discusses some of the evidence for his evolutionary hypothesis that religions are adaptive at the group level, providing practical benefits relating to the specific conditions the group is confronted with...Given the central importance of evolution in biology, the most extraordinary thing about the public's view, Wilson points out, is not that 50 percent don't believe it, but that nearly 100 percent haven't connected it to anything of importance in their lives. One of Wilson's chief goals—one he accomplishes admirably—is to demonstrate the relevance and value of evolutionary biology not just to scientists but to ordinary people. In story after engaging story, he conveys not only the sweep and the power of evolutionary thinking but the grandeur, as Darwin put it, of this view of life. By the end of the book, the reader understands Wilson's metaphor that evolution is an artist that has helped fashion the sculpture that is the living world.

The Outsourced Brain

I can't resist passing on this clever NY Times Op-Ed piece by David Brooks - on the subject of the dissolution of our individual intelligences into the mush of the infosphere.

Different takes on the social brain.

Gobbini et al. show that different types of mentalizing engage different brain regions. The abstract and a summary figure:

We compared two tasks that are widely used in research on mentalizing—false belief stories and animations of rigid geometric shapes that depict social interactions—to investigate whether the neural systems that mediate the representation of others' mental states are consistent across these tasks. Whereas false belief stories activated primarily the anterior paracingulate cortex (APC), the posterior cingulate cortex/precuneus (PCC/PC), and the temporo-parietal junction (TPJ)—components of the distributed neural system for theory of mind (ToM)—the social animations activated an extensive region along nearly the full extent of the superior temporal sulcus, including a locus in the posterior superior temporal sulcus (pSTS), as well as the frontal operculum and inferior parietal lobule (IPL)—components of the distributed neural system for action understanding—and the fusiform gyrus. These results suggest that the representation of covert mental states that may predict behavior and the representation of intentions that are implied by perceived actions involve distinct neural systems. These results show that the TPJ and the pSTS play dissociable roles in mentalizing and are parts of different distributed neural systems. Because the social animations do not depict articulated body movements, these results also highlight that the perception of the kinematics of actions is not necessary to activate the mirror neuron system, suggesting that this system plays a general role in the representation of intentions and goals of actions. Furthermore, these results suggest that the fusiform gyrus plays a general role in the representation of visual stimuli that signify agency, independent of visual form.

Figure - Locations of loci of activations associated with ToM, social animation, and biological motion tasks, projected onto the left and right lateral surfaces of the brain.

Brain changes after rehabilitation of congenital prosopagnosia

Another article on faces...Degutis et al. show MRI changes correlating with a recovery of enhanced amplitude of the N170 ERP (electroencephalogram event related potential)component in response to faces compared to objects after training of a subject with congenital prosopagnosia (face blindness).

We used functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to measure neural changes associated with training configural processing in congenital prosopagnosia, a condition in which face identification abilities are not properly developed in the absence of brain injury or visual problems. We designed a task that required discriminating faces by their spatial configuration and, after extensive training, prosopagnosic MZ significantly improved at face identification. Event-related potential results revealed that although the N170 was not selective for faces before training, its selectivity after training was normal. fMRI demonstrated increased functional connectivity between ventral occipital temporal face-selective regions (right occipital face area and right fusiform face area) that accompanied improvement in face recognition. Several other regions showed fMRI activity changes with training; the majority of these regions increased connectivity with face-selective regions. Together, the neural mechanisms associated with face recognition improvements involved strengthening early face-selective mechanisms and increased coordination between face-selective and nonselective regions, particularly in the right hemisphere.

The male chill-out after sex: role for brain oxytocin

Here is an intriguing account from Waldherr and Neumann:

Sexual activity and mating are accompanied by a high level of arousal, whereas anecdotal and experimental evidence demonstrate that sedation and calmness are common phenomena in the postcoital period in humans. These remarkable behavioral consequences of sexual activity contribute to a general feeling of well being, but underlying neurobiological mechanisms are largely unknown. Here, we demonstrate that sexual activity and mating with a receptive female reduce the level of anxiety and increase risk-taking behavior in male rats for several hours. The neuropeptide oxytocin has been shown to exert multiple functions in male and female reproduction, and to play a key role in the regulation of emotionality after its peripheral and central release, respectively. In the present study, we reveal that oxytocin is released within the brain, specifically within the hypothalamic paraventricular nucleus, of male rats during mating with a receptive female. Furthermore, blockade of the activated brain oxytocin system by central administration of an oxytocin receptor antagonist immediately after mating prevents the anxiolytic effect of mating, while having no effect in nonmated males. These findings provide direct evidence for an essential role of an activated brain oxytocin system mediating the anxiolytic effect of mating in males.

It's in the Eyes!

Another curious bit on our brain's specialization for recognizing faces, noting the central role of the eyes. The abstract and a figure:

Unlike most other objects that are processed analytically, faces are processed configurally. This configural processing is reflected early in visual processing following face inversion and contrast reversal, as an increase in the N170 amplitude, a scalp-recorded event-related potential. Here, we show that these face-specific effects are mediated by the eye region. That is, they occurred only when the eyes were present, but not when eyes were removed from the face. The N170 recorded to inverted and negative faces likely reflects the processing of the eyes. We propose a neural model of face processing in which face- and eye-selective neurons situated in the superior temporal sulcus region of the human brain respond differently to the face configuration and to the eyes depending on the face context. This dynamic response modulation accounts for the N170 variations reported in the literature. The eyes may be central to what makes faces so special.

Figure - Simplified neural model of early face processing. Three sources are simultaneously active around 170 msec poststimulus onset. One source in the superior temporal sulcus (STS) region with a radial orientation generates the ERP N170 component. The combination of tangential sources in the fusiform gyrus (FG) and middle occipital gyrus (MOG) generates the MEG M170. The dynamic response modulation of eye- and face-selective neurons within the STS accounts for inversion and CR effects on the face N170 amplitude and for the other existing ERP data on the N170. The + signs represent the amount of activation of the neurons. The absence of + signs signifies that the neurons are not responding.

Our visual system is tuned to animals.

New et al. argue that the human attention system evolved category-specific selection criteria to monitor animals (including humans) in the environment. Ohman gives a nice commentary that puts the work in perspective (PDF here) Below is the abstract and a figure from New et.al. (PDF of article here):

Visual attention mechanisms are known to select information to process based on current goals, personal relevance, and lower-level features. Here we present evidence that human visual attention also includes a high-level category-specialized system that monitors animals in an ongoing manner. Exposed to alternations between complex natural scenes and duplicates with a single change (a change-detection paradigm), subjects are substantially faster and more accurate at detecting changes in animals relative to changes in all tested categories of inanimate objects, even vehicles, which they have been trained for years to monitor for sudden life-or-death changes in trajectory. This animate monitoring bias could not be accounted for by differences in lower-level visual characteristics, how interesting the target objects were, experience, or expertise, implicating mechanisms that evolved to direct attention differentially to objects by virtue of their membership in ancestrally important categories, regardless of their current utility.

Sample stimuli with targets circled. Although they are small (measured in pixels), peripheral, and blend into the background, the human (A) and elephant (E) were detected 100% of the time, and the hit rate for the tiny pigeon (B) was 91%. In contrast, average hit rates were 76% for the silo (C) and 67% for the high-contrast mug in the foreground (F), yet both are substantially larger in pixels than the elephant and pigeon. The simple comparison between the elephant and the minivan (D) is equally instructive. They occur in a similar visual background, yet changes to the high-contrast red minivan were detected only 72% of the time (compared with the smaller low-contrast elephant's 100% detection rate).