Neuroscience posts
- February 7, 2010
- 12:25 AM
- 560 views
Psychodynamic Psychotherapy in the Scanner?
by The Neurocritic in The Neurocritic
Arrangement for psychotherapy fMRI studies using the couch of Sigmund Freud.[No not really, although the authors did stretch the implications of their findings in the Discussion...]Whether the proprietors of this blog want to admit it or not, neuropsychoanalysis appears to be a new field of study. What does psychoanalysis do to the brain? In a new Psychotherapy Research paper, Loughead et al. (2010) collected autobiographical relationship narratives from 16 healthy control participants free of any psychiatric or neurological ailments. These types of vignettes were used as stimuli because "people in psychotherapy spontaneously recall and tell stories about their relationships with other people..." A series of 14 one minute narratives was collected from each subject using the Relationships Anecdotes Paradigm (RAP) method, a structured interview designed to elicit descriptions of meaningful life events with another person. The participants then rated each episode on a 5-point Likert scale for positive and negative emotions.The investigators rated the narratives in another fashion to extract common themes. The core conflictual relationship theme (CCRT) method (Luborsky & Crits-Christoph, 1998) is a psychotherapy instrument used to measure patterns within interpersonal relationships:From a content analysis of the relationship narratives, it is possible to identify three kinds of relationship components: (a) wishes (wishes, intentions, goals of the individual or self); (b) responses from the other to the self; and (c) responses of the self to the other...The main CCRT relationship patterns are defined as the most repetitive relationship themes across an individual’s relationship narratives, usually those ranking first and second in frequency across the narratives. These main CCRTs have been a focus for the conduct of both psychotherapy and psychotherapy research (Luborsky & Crits-Christoph, 1998).Then a neuroimaging study was conducted with 11 of the participants (5 were ultimately tossed out for various reasons). It's notable that all subjects were free of psychiatric disorders, and none were in therapy. So the direct application of the results to psychotherapy practice is questionable. That said, what were the experimental procedures? For the narratives,The two most repetitive wishes (W), responses from others (RO), and responses of self (RS) were identified for each participant’s set of 14 narratives. These repetitive themes are hereafter referred to as the main CCRTs. Weighted scores were then assigned to each narrative based on the frequency with which the participant’s main CCRT themes appeared in her or his 14 narratives. For example, if a participant’s main RO was "hurt me" and it appeared in seven of 14 narratives, then each narrative containing the RO "hurt me" received a weighted score of 7....The weighted scores for the other elements were tallied up, and 3 narratives each were selected for the high and the low CCRT/emotion conditions [NOTE: these two factors could not be distinguished from each other]. In addition, narratives from one of the excluded participants served as the control, non-autobiographical relationship episodes:...The control episodes were selected to be similar to the personal condition in narrative structure, emotion, and CCRT content and yet have no autobiographical relevance to the participant.The three types of stimuli were presented in a block design: six 30-s blocks of personal narratives and six 30-s blocks of control narratives (half high, half low CCRT/emotion), with resting baseline thrown in for good measure. A sample CCRT narrative is shown below (click on image for a larger view).Figure I (Loughead et al. (2010). Sample CCRT relationship episode.The fMRI results came as no surprise to anyone: personal autobiographical memories activate the brain to a greater extent than someone else's memories. Wow!The network of frontal and parietal regions observed for the main effect of narrative type, which includes the anterior cingulate, precuneus/posterior cingulate, inferior frontal gyrus, inferior parietal lobule, and middle frontal gyri, is consistent with the existent neuroimaging literature on recall of autobiographical memories (Buckner & Carroll, 2007...).Figure II (Loughead et al. (2010). Brain images showing group main effect for narrative type (personal, control). Statistical parametric maps are displayed in radiological convention (left is right) standardized into Talairach space. ACC, anterior cingulate; Inf Front, inferior frontal gyrus; Mid Front, middle frontal gyrus; Inf Parietal; inferior parietal lobule. No voxels were above threshold for CCRT/emotion (high, low) main effect or the interaction.And there was absolutely no difference in brain activity elicited by the low CCRT and high CCRT conditions. So much for the CCRT method, at least in this non-psychiatric population. However, exploratory analyses showed correlations between BOLD signal and CCRT score in the left hippocampus, parahippocampal gyrus, and middle occipital gyrus. Not in the amygdala, however. The lack of main effect or interaction for the main variable of interest did not prevent the authors from speculating wildly:Our exploratory analysis suggests that narratives characterized by increasing amounts of the most repetitive (i.e., main CCRT patterns) are special from a neurobiological perspective... When narratives are high in CCRT content, this is somewhat akin to exposing, or reflecting back, the main CCRT themes to a patient (i.e., providing a transference interpretation). Thus, an area of further study suggested by these results is how exposure to the main CCRT themes (or transference interpretation) could modulate brain activation in the medial temporal and occipital lobes in treatment populations.Never mind that no psychotherapist was involved at all, since none of the participants were In Treatment. And what wild speculation would be complete without... MIRROR NEURONS!Memories, the self, and emotion have long been of interest to psychotherapy, and theory of mind/mentalization and the mirror neuron system have been proposed as specific mechanisms of psychotherapy process (Fonagy & Bateman 2006...). These results demonstrate that the essential psychotherapy activity of recall of autobiographical relationship episodes engages neural substrates for systems that have been identified by research as central for psychotherapy process.... Read more »
Loughead, J., Luborsky, L., Weingarten, C., Krause, E., German, R., Kirk, D., & Gur, R. (2010) Brain activation during autobiographical relationship episode narratives: A core conflictual relationship theme approach. Psychotherapy Research, 1-16. DOI: 10.1080/10503300903470735
- February 5, 2010
- 05:53 AM
- 815 views
the rise of neuroscience
by Alex Holcombe in ceptional
So I knew neuroscience has exploded over the last few decades, but I didn’t know its emergence as a more autonomous discipline is “the biggest structural change in scientific citation patterns over the past decade”. In the authors’ words that follow, they are referring to their figure showing neuroscience emerging as a new citation [...]... Read more »
Rosvall, M., & Bergstrom, C. (2010) Mapping Change in Large Networks. PLoS ONE, 5(1). DOI: 10.1371/journal.pone.0008694
- February 4, 2010
- 09:30 PM
- 999 views
Can unconscious brains think? Coma, philosophy of mind, and the media.
by Michael Slezak in Good, Bad, and Bogus
“Ok brain. I don’t like you and you don’t like me. Let’s just do this and I can go back to killing you with beer.” - Homer Simpson
A new piece of research has elicited headlines around the world in today’s newspapers such as “Coma patient ‘talks’ with his thoughts” and “Coma victim talks via brain [...]... Read more »
Monti MM, Vanhaudenhuyse A, Coleman MR, Boly M, Pickard JD, Tshibanda L, Owen AM, & Laureys S. (2010) Willful Modulation of Brain Activity in Disorders of Consciousness. The New England journal of medicine. PMID: 20130250
Martin M. Monti, & Audrey Vanhaudenhuyse. (2010) Willful Modulation of Brain Activity in Disorders of Consciousness. The New England Journal of Medicine. info:/10.1056/NEJMoa0905370
- February 4, 2010
- 04:06 PM
- 980 views
Adult neurogenesis in humans: Murine Features of Neurogenesis in the Human Hippocampus
by Jason Snyder in Functional Neurogenesis
Studies of adult neurogenesis often begin with the following sentence: “Adult neurogenesis occurs in all mammals examined, including humans.” More detail-oriented papers might say, “Adult neurogenesis occurs in all mammals examined, including humans…but not bats.” Here, the similarities between bats and humans become more evident than one might expect: it could be an equally long [...]... Read more »
Knoth, R., Singec, I., Ditter, M., Pantazis, G., Capetian, P., Meyer, R., Horvat, V., Volk, B., & Kempermann, G. (2010) Murine Features of Neurogenesis in the Human Hippocampus across the Lifespan from 0 to 100 Years. PLoS ONE, 5(1). DOI: 10.1371/journal.pone.0008809
- February 4, 2010
- 01:35 PM
- 1,080 views
The cutaneous rabbit illusion hops out of the body
by Mo in Neurophilosophy
IF a rapid series of taps are applied first to your wrist and then to your elbow, you will experience a perceptual illusion, in which phantom sensations are felt along the skin connecting the two points that were actually touched. This feels as if a tiny rabbit is hopping along your skin from the wrist to the elbow, and is therefore referred to as the "cutaneous rabbit". The illusion indicates that our perceptions of sensory inputs do not enter conscious awareness until after the integration of events occuring within a certain time window, and that the sensory events taking place at a certain point can be influenced by future events.
A group of Japanese researchers now shows that this illusion is not confined to the body. In a new study published today in the Journal of Neuroscience, they report that the cutaneous rabbit can easily be induced to "hop out" of the body, so that the illusory sensations are perceived not from the body itself, but from external objects that interact with it.
Read the rest of this post... | Read the comments on this post...... Read more »
Miyazaki, M., Hirashima, M., & Nozaki, D. (2010) The "Cutaneous Rabbit" Hopping out of the Body. Journal of Neuroscience, 30(5), 1856-1860. DOI: 10.1523/JNEUROSCI.3887-09.2010
- February 4, 2010
- 08:00 AM
- 879 views
Can crayfish feel electricity?
by Zen Faulkes in NeuroDojo
The sensory abilities of vertebrates and invertebrates are generally more similar than they are different: both groups can detect light, sound, pressure, and so on. One of the few cases of a sensory ability that seemed to be the domain of vertebrates alone was the ability to detect electrical signals: electroreception. Several fish have it, and use electrical signals to communicate. Platypus have it. Electroreception in fish is one of the best examples of
For a long time, people argued that invertebrates don’t have electroreception, for reasons that were perhaps a bit idiosyncratic. One explanation I heard given was that something like a crayfish was too small. And I’ve seen crayfish much bigger than knifefish.
A few years ago, a couple of papers came out that started to pick apart that idea, and showed that crayfish could respond to electrical signals. This new paper by Patullo and Macmillan* pushes the state of the art forward in a couple of ways (And it does so with some rather graceful prose, I might add.)
First, it expands the number of species. The authors used Cherax destructor, which they’d used in a previous study, and also tested Cherax quadricarinatus (pictured). Both species decreased their activity in the presence of electric fields, at about the same intensity levels.
The intensity levels were the second way this paper pushed things forward: it showed that crayfish were responding to much lower levels of electricity than previous studies – about ten times lower. Because neurons run on electricity, if you give an intense enough signal, animals will respond, even if they have no specialized sensory apparatus for detecting electical fields. This paper goes further towards suggesting that crayfish can respond to a biologically relevant electrical signal. And, indeed, one of the key features is that the electrical signal played to the crayfish was derived from a swimming tadpole, which crayfish will prey upon.
These experiments seem rather tricky to pull off and calibrate. Behavioural analysis is complicated by there not be any particular behaviour identified (yet!) that is reliably and consistently evoked by an electrical signal. This is going to make the next stage of this research, locating the neurons responsible for crayfish electroreception, a challenge.
* Full disclosure: I have worked with both authors on this paper, so I think of them as Blair and David. And, as an example of how long it takes to get things out in science, I helped them start this project over ten years ago.
Crossposted at Marmorkrebs blog.
Reference
Patullo, B., & Macmillan, D. (2010). Making sense of electrical sense in crayfish Journal of Experimental Biology, 213 (4), 651-657 DOI: 10.1242/jeb.039073... Read more »
Patullo, B., & Macmillan, D. (2010) Making sense of electrical sense in crayfish. Journal of Experimental Biology, 213(4), 651-657. DOI: 10.1242/jeb.039073
- February 3, 2010
- 11:55 PM
- 399 views
Neury Thursday: Recent Success with Neural Stem Cells
by Allison in Dormivigilia
Neural stem/progenitor cells have been co-grafted with growth factors into damaged spinal cord tissue. Prior to this, the tissue was infused with an enzyme that not only reduces chondroitin sulfate proteoglycans, which appear in the CNS following damage, but also increases the survival of the neural stem cells. The article can be found in this week's Journal of Neuroscience... Read more »
Soheila Karimi-Abdolrezaee, Eftekhar Eftekharpour, Jian Wang, Desiree Schut, and Michael G. Fehlings. (2010) Synergistic Effects of Transplanted Adult Neural Stem/Progenitor Cells, Chondroitinase, and Growth Factors Promote Functional Repair and Plasticity of the Chronically Injured Spinal Cord. Journal of Neuroscience. info:/10.1523/JNEUROSCI.3111-09.2010
- February 3, 2010
- 07:13 PM
- 781 views
Brodmann's Map -- 101 years old
by Greg Hickok in Talking Brains
In celebration of the centenary of the publication of Korbinian Brodmann's famous map, Karl Zilles & Katrin Amunts have just published a great little piece on its history and current influence (too bad Nature Reviews Neuroscience couldn't have brought it to press in 2009). The paper highlights some interesting tidbits, like the influence of evolutionary theory on Brodmann's work, how Brodmann's map relates to those that followed, how it lost favor and how it was given new life with the advent of functional imaging. The paper even features an interview with Korbinian himself (fictitious, of course). Beyond the interesting historical perspective, the article underscores the pitfalls associated with over-interpreting Brodmann areas in functional imaging studies, but also emphasizes the importance of anatomy in developing models of the organization of the cerebral cortex. Zilles K, & Amunts K (2010). Centenary of Brodmann's map - conception and fate. Nature reviews. Neuroscience, 11 (2), 139-45 PMID: 20046193... Read more »
Zilles K, & Amunts K. (2010) Centenary of Brodmann's map - conception and fate. Nature reviews. Neuroscience, 11(2), 139-45. PMID: 20046193
- February 3, 2010
- 04:00 PM
- 1,294 views
Where is my back?
by Lorimer Moseley in BodyInMind
Chronic pain is associated with a loss of the normal capacity to know where your body is. Chronic pain is also associated with odd bodily feelings. To find out if people with chronic back pain had trouble ‘feeling’ their back, they were asked to draw on a piece of paper the outline of where they felt [...]... Read more »
Lorimer Moseley. (2010) I can't find it!. BodyinMind. info:/
- February 3, 2010
- 03:58 PM
- 643 views
Brodmann's Map 100 Years Later
by Neuropsych15 in The MacGuffin
Brodmann's map. Anyone who has taken a course in basic neuroanatomy has been exposed to his roadmap of the cerebral cortex. In this month's Nature Reviews Neuroscience, Zilles and Amunts (1) dedicated an article to Korbinian Brodmann and his map, celebrating its 100th anniversary (Brodmann's original work was published in 1909). First, a little background. Brodmann's original map contains 52 areas; however, areas 12-16 and 48-51 are only found in nonhuman primate brains, so only 43 areas are actually labeled. How Brodmann constructed his "map" is quite complicated. He made numerous razor thin, horizontal slices of human brains. He then stained the cell bodies within those slices and attributed a number to an area if it was cytoarchitectonically distinct from its neighboring areas of the cortex.Many others followed Brodmann's work with maps of their own. According to the article,"During the next three decades, Otfried Foerster, Alfred Walter Campbell, Grafton Elliott Smith, Constantin Freiherr von Economo and Georg N. Koskinas argued for localizable anatomical and functional correlation and the segregation of cortical entities" Many of those names may be new to you, which highlight how influential Brodmann's work has been. The reason there are many different "maps" is because brain mapping is not an exact science. Trying to differentiate the cortex based on brain architecture can produce profoundly different results, depending on the staining technique that is used and on the researcher's subjectivity."The Vogts used myelin-stained histological sections to study brain architecture (that is, myeloarchitecture). Their myeloarchitectonic map has many more areas (a total of 200) than that of Brodmann, because the Vogts further subdivided the Brodmann areas on the basis of the regionally more differentiated architecture of intracortical nerve fibres."Below is a comparison of the various "maps" that have been produced since Brodmann's work in 1909.(click to enlarge)Differences between all these brain maps are apparent. However, there is also considerable overlap, suggesting that there is some degree of observer independence, reproducibility, and objectivity to the process.A little historical note for anyone who was forced to memorize all those Brodmann areas, but was hampered by its apparent lack of logic (areas 1,2,3, start in the mid-lateral areas, while the remaining numbers are distributed in a quasi-random order). Each area number was assigned based on the order in which he prepared a slide, hence the apparent randomness of number assignment. In his time, testing whether each "area" was correlated to a specific function was quite difficult. Over time, as other "maps" were published and his original became criticized for lack of objectivity, his map fell out of fashion. That is until the 1980's, when various brain imaging techniques were developed. Being able to image a live human during the performance of a specific task, it became possible to associate functional data with cytoarchitectual data. It was Brodmann's map that become apart of many of the first software and sterotaxic atlases for these machines.Brodmann's work helped to revolutionize modern neuroscience. While many other maps have followed Brodmann's, and even though contemporary research has shown that "his map is incomplete or even wrong in some of the brain regions," many of the areas do correlate very well with various functional areas of the cortex, which is why his work still has relevance 100 years later. Zilles K, & Amunts K (2010). Centenary of Brodmann's map - conception and fate. Nature reviews. Neuroscience, 11 (2), 139-45 PMID: 20046193... Read more »
Zilles K, & Amunts K. (2010) Centenary of Brodmann's map - conception and fate. Nature reviews. Neuroscience, 11(2), 139-45. PMID: 20046193
- February 3, 2010
- 08:00 AM
- 507 views
When the going gets tough, do the puffs get going?
by Zen Faulkes in NeuroDojo
You would think that having a dedicated set of neurons that triggered super-fast escape responses to get away from fast predator attacks and other sudden events in your area would be something that you’d want to keep around. This is usually so, but it turns out, not always. This is a problem I’ve been struggling with for some time now, and I’m thrilled to bits to find another example.
Fish have a group of neurons that trigger escape responses called C-starts, so called because the fish bends in a C shape away from the source of the stimulus. The largest of these neurons – large enough to be called giant neurons – are Mauthner cells, named after their discoverer. Bigger neurons send faster signals, so if Mauthner neurons are inactivated experimentally, fish can do C-starts, but they’re slower at it.
Anna Greenwood and colleagues have now found an interesting case of a natural experiment: two fairly similar fishes that differ dramatically in their responses to startling stimuli. They’re two different pufferfish: the green puffer (Tetraodon nigroviridis; below left) and the long-spine porcupinefish (Diodon holocanthus; below right).
Give these two animals the same sudden sound, and both will respond... but the green puffer is much faster, performing a classic C-start (start of movement marked with asterisk in first row of silhouettes). The porcupinefish takes twice as long to react (second row of silhouettes), and doesn’t bend nearly as much.
The neural anatomy correlates with these differences in behaviour. Large Mauthner cells in green puffers, no large Mauthner cells in porcupinefish. The position of the Mauthner cells is consistent enough that Greenwood and colleagues were able to provide argue that the Mauthner cells are missing in porcupinefish, not just tiny.
Greenwood and company suggest two scenarios where the Mauthner cells might be lost. There might be relaxed selection on the trait, and it’s lost sort of by happenstance, a little like how cave dwelling organisms tend to lose pigments or eyes.
Alternately, there might be some active disadvantage to having the Mauthner cells. For the porcupinefish, that disadvantage might be that Mauthner cells and C-starts interfere with a dramatically different anti-predator behaviour: inflation. Greenwood and company don’t provide hard numbers, but report that porcupinefish are much more likely than green puffers to do the classic behaviour that gives puffers their names.
The result of all of this detailed behavioural analysis and anatomical work is... to send researchers back to the field. To understand what drove their neurobehavioural changes, we’ve got to get a better handle of the differing ecology of these species.
Reference
Greenwood, A., Peichel, C., & Zottoli, S. (2010). Distinct startle responses are associated with neuroanatomical differences in pufferfishes Journal of Experimental Biology, 213 (4), 613-620 DOI: 10.1242/jeb.037085... Read more »
Greenwood, A., Peichel, C., & Zottoli, S. (2010) Distinct startle responses are associated with neuroanatomical differences in pufferfishes. Journal of Experimental Biology, 213(4), 613-620. DOI: 10.1242/jeb.037085
- February 3, 2010
- 07:05 AM
- 595 views
Imaging the Brain Better, Faster,Thinner
by Neuroskeptic in Neuroskeptic
A lot of the studies that I cast my Neuroskeptical eye over are related to functional magnetic resonance imaging (fMRI).This is because, in my opinion, quite a lot of today's fMRI work suffers from methodological flaws. But that's not to say that all fMRI work is suspect, or, worse, that there's something inherently unscientific about fMRI as such. fMRI's a tool, an amazing one in a lot of ways, but like any tool it needs to be used well. Along with others, I've criticized various aspects of recent fMRI practice, but only because it's frustrating to see such a powerful tool not being used to its full potential.So I was very pleased by a recent paper by Sabatinelli et al, The Timing of Emotional Discrimination in Human Amygdala and Ventral Visual Cortex. The authors set out to test a hypothesis - that seeing an emotionally charged picture would activate the amygdala and the inferotemporal cortex (IT) before activating the extrastriate occipital cortex.This is what should happen according to an influential model of how the brain processes emotionally meaningful information; the theory goes that the amygdala is part of a rapid "emotion detector" pathway, which responds faster than the standard visual perceptual system. You see that it's scary before you see what it is, in other words.To test the prediction, they scanned a single 5mm slice of the brain - see above - which cut through all of the regions of interest given the hypothesis. Most fMRI studies image the whole brain, but because scanning takes time, this produces one whole-brain image every 2 or 3 seconds.Sabatinelli et al's single slice approach gave them 10 scans/second, which was crucial given that they were concerned with detecting which parts of the brain activated first. They scanned people while showing them a series of pictures. Some were boring images with no emotional impact, some were "positive" (i.e. porn), and others were "negative" (bloody pictures of mutilation).The results are on the left. All images activated the visual system more than a blank screen did, unsurprisingly. Both kinds of "emotional" pictures activated the amygdala, IT, and more than the boring ones did (the green line), which is reassuring, since if they didn't, the basic assumptions of the experiment would be in question. And crucially, the emotional vs. non-emotional difference occurred about up to 1s earlier in the amygdala and the IT than in the mOcc (extrastriate occipital cortex), in line with the original predictions.In itself, this doesn't prove the "rapid emotion pathway" model, but it's an important piece of supporting evidence. It's also a great example of the flexibility of fMRI; while it's often thought of as a way to detect where neural activation happens, as opposed to when, with the right scanning parameters, it doesn't have to be that way. Although there's an unavoidable time lag in the BOLD response that fMRI measures - the response peaks about 5 seconds after the brain cells actually fire - this doesn't stop you from investigating the relative timing of activation in different areas, as in this study.The key was that Sabatinelli et al had a specific hypothesis and designed their experiment to test it, as opposed to just scanning people under some conditions and looking to see which parts of the brain lit up - fishing for blobs, as it's known. fMRI is a very powerful tool for blob-fishing, unfortunately. But it's also a powerful tool for doing more informative science.Sabatinelli D, Lang PJ, Bradley MM, Costa VD, & Keil A (2009). The timing of emotional discrimination in human amygdala and ventral visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29 (47), 14864-8 PMID: 19940182... Read more »
Sabatinelli D, Lang PJ, Bradley MM, Costa VD, & Keil A. (2009) The timing of emotional discrimination in human amygdala and ventral visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29(47), 14864-8. PMID: 19940182
- February 2, 2010
- 04:37 PM
- 1,231 views
Optimising Fat Burning on Non-HIIT days
by mc in begin to dig (b2d)
We can't HIIT all the time, nor can we work steady state at the top end of our aerobic capacit all the time. Our central nervous system would come up and strangle us. That's another word for overtraining. But if we still want to make sure that we're optimizing our non-HIIT time for both endurance capacity and fat mobilization, can we do both at the same time? Outlook looks good that there's a sweet spot for such work in the 60-80% MaxHR zone.... Read more »
Carey, DG. (2009) Quantifying Differences in the "Fat Burning" Zone and the Aerobic Zone: Implications For Training. Journal of Strength and Conditioning Research: , 23(7), 2090-2095. info:/10.1519/JSC.0b013e3181bac5c5
- February 2, 2010
- 04:01 PM
- 578 views
Instant Neurons
by Kevin Mitchell in Wiring the Brain
A new study from Marius Wernig and colleagues at Stanford University has succeeded in transforming fibroblast cells directly into neurons. In the end, it was far simpler than expected. The identities of different cell types are known to be established during development by particular combinations of transcription factors, which, by controlling the expression of large numbers of target genes, define the genetic and biochemical profile of each cell type. It was thought that this profile of gene expression was then locked into place by chromatin proteins which bind to DNA and fix it into an active or inactive conformation. Over development, the passage from an early embryonic cell, with full potential to generate any cell type, to more differentiated cells, was believed to be unidirectional and irreversible. The ability to clone an animal, by transferring the nucleus of a differentiated cell into a fertilised, enucleated oocyte, showed that, in fact, the profile of gene expression could be reversed, wiped clean and restored to a pristine, undifferentiated state. Groundbreaking experiments over the last few years, led by Shinya Yamanaka and colleagues, have established an even simpler method to take a differentiated somatic cell and convert it back to an undifferentiated state, a so-called induced pluripotent stem cell (iPS cell). This is achieved by forcing the expression of a set of transcription factors that define the stem cell fate – in essence, driving the biochemical profile to a stem cell pattern. Auto- and cross-regulatory interactions between these transcription factors and others in the cell ensure a stable transformation of cell identity. So, one can take a differentiated cell and reverse the direction of development, driving it back to an undifferentiated state. This is obviously a hugely powerful technique as the iPS cells can then be differentiated in vitro into many other cell types, for research or clinical purposes. What was not clear, however, was how general this strategy might be. Was there something special about the stem cell fate or could the same approach be used to convert one differentiated cell-type directly into another, without having to go via a stem cell intermediate? Wernig and colleagues have now shown that this can be done. They forced fibroblasts, derived from either embryonic or adult mice, to express a combination of three transcription factors which characterise a general neuronal fate, by transfecting them with lentiviruses carrying these genes. These genes, Ascl, Brn2 and Mytl1, were defined from an initial set of nineteen candidates based on genes known to be important in neuronal differentiation during development. Transfection with these genes very efficiently, over a period of several days, transformed the fibroblasts into neurons. They express neuronal proteins, show a neuronal morphology, elaborate axons and dendrites, have characteristic electrical membrane properties, fire action potentials and even synapse with each other. By all possible criteria, these are neurons. In particular, 99% of them seem to be glutamatergic and many express markers characteristic of cortical neurons. One can expect a flurry of follow-on studies using different combinations of transcription factors to drive cells into a variety of more specific neuronal subtypes – likely to include dopaminergic neurons, motor neurons, photoreceptors and many others – as well as non-neuronal cell types. There is every reason to expect the same approach will work with human cells, as was the case with the iPS cell technology. This will offer a rapid and very efficient method to generate a large supply of neurons from individuals with their own genotype. These are most obviously of possible use in cell replacement therapies for neurodegenerative disease, though the prospect of this in clinical practice remains some years off. The value for clinical research is also immense, and likely more immediate. The ability to grow neurons with the genotypes of patients with psychiatric or neurological disorders, for example, offers a kind of virtual biopsy – access to neurons of the patient previously unobtainable. This will allow analysis of the possible genetic defects in each patient and their cellular consequences, likely to be invaluable in elucidating pathogenic mechanisms at a molecular level. The future is now.Vierbuchen, T., Ostermeier, A., Pang, Z., Kokubu, Y., Südhof, T., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors Nature DOI: 10.1038/nature08797... Read more »
Vierbuchen, T., Ostermeier, A., Pang, Z., Kokubu, Y., Südhof, T., & Wernig, M. (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature. DOI: 10.1038/nature08797
- February 1, 2010
- 04:11 PM
- 1,103 views
Addiction Behavior in One Protein
by Rob Mitchum in ScienceLife
Addiction is a hard disease to define. We all understand in a general sense what addiction to drugs or sex or food means or looks like, but when it comes to an explicit definition, even the experts struggle. In the DSM-IV, the manual for psychiatric disease, addiction is bifurcated into “substance abuse” and “substance dependence,” [...]... Read more »
Loweth, J., Singer, B., Baker, L., Wilke, G., Inamine, H., Bubula, N., Alexander, J., Carlezon, W., Neve, R., & Vezina, P. (2010) Transient Overexpression of -Ca2 /Calmodulin-Dependent Protein Kinase II in the Nucleus Accumbens Shell Enhances Behavioral Responding to Amphetamine. Journal of Neuroscience, 30(3), 939-949. DOI: 10.1523/JNEUROSCI.4383-09.2010
- February 1, 2010
- 09:08 AM
- 1,463 views
Objective Diagnosis Of PTSD Using Magnetoencephalography
by j7uy5 in The Corpus Callosum
Objective diagnosis is in some
ways the holy grail of medicine. It has been maddeningly elusive
in psychiatry. Now comes a paper in which the authors suggest
that they may have found this treasure.
The paper details a method of using magnetoencephalography to assess
human brain function. They claim that, in a select population, it
can correctly identify patients with PTSD with 90% accuracy.
The
synchronous neural interactions test as a functional neuromarker for
post-traumatic stress disorder (PTSD): a robust classification
method based on the bootstrap
A P Georgopoulos et
al 2010 J. Neural Eng. 7 016011
Abstract. Traumatic experiences can produce
post-traumatic stress disorder (PTSD) which is a debilitating condition
and for which no biomarker currently exists (Institute of Medicine (US)
2006 Posttraumatic Stress Disorder: Diagnosis and Assessment
(Washington, DC: National Academies)). Here we show that the
synchronous neural interactions (SNI) test which assesses the
functional interactions among neural populations derived from
magnetoencephalographic (MEG) recordings (Georgopoulos A P et al 2007
J. Neural Eng. 4 349-55) can successfully differentiate PTSD patients
from healthy control subjects. Externally cross-validated,
bootstrap-based analyses yielded >90% overall accuracy of
classification. In addition, all but one of 18 patients who were not
receiving medications for their disease were correctly classified.
Altogether, these findings document robust differences in brain
function between the PTSD and control groups that can be used for
differential diagnosis and which possess the potential for assessing
and monitoring disease progression and effects of therapy.
The synchronous neural interactions test is a test that is done by
having persons perform a simple task, while the magnetic signals from
their brain are being measured. The process is called magnetoencephalography.
The resulting record is called a magnetoencephalogram (MEG). It
is similar to an electroencephalogram (EEG). The difference is
that the EEG measures small electric currents. The MEG measures
magnetic impulses. These impulses are only slightly affected by
the intervening tissue (skull, skin, etc). Therefore, it is
possible to get readings that are more precise. The downside is
that it requires a more elaborate device, and a special,
magnetically-shielded, room. Very few of these devices exist.
Read the rest of this post... | Read the comments on this post...... Read more »
Georgopoulos, A., Tan, H., Lewis, S., Leuthold, A., Winskowski, A., Lynch, J., & Engdahl, B. (2010) The synchronous neural interactions test as a functional neuromarker for post-traumatic stress disorder (PTSD): a robust classification method based on the bootstrap. Journal of Neural Engineering, 7(1), 16011. DOI: 10.1088/1741-2560/7/1/016011
- January 31, 2010
- 04:30 PM
- 1,164 views
Back pain- Neil OConnell on local muscles going global
by Lorimer Moseley in BodyInMind
We’ve known for a while that people with chronic back pain move differently. Normally when you are going to wave your arm or leg the deep spinal muscles kick in just beforehand, perhaps to provide stability. In back pain the activity of some of the deep back muscles is delayed in response to spine and [...]... Read more »
Jacobs JV, Henry SM, & Nagle KJ. (2010) Low back pain associates with altered activity of the cerebral cortex prior to arm movements that require postural adjustment. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. PMID: 20071225
- January 30, 2010
- 05:12 PM
- 629 views
Is Depression Undertreated?
by Neuroskeptic in Neuroskeptic
Neuroskeptic readers will be familiar with the idea that too many people are being treated for mental illness. But not everyone agrees. Many people argue that common mental illnesses, such as depression, are undertreated. Take, for example, a paper just out in the esteemed Archives of General Psychiatry: Depression Care in the United States: Too Little for Too Few.The authors looked at the results of three large (total N=15,762) surveys designed to measure the prevalence of mental illness in American adults. I've described how these surveys are conducted before: they took a randomly selected representative sample of Americans, and asked them a standardized series of questions (the CIDI interview) about their mood and emotions, in order to try to diagnose mental illness. The interviewers, while trained, were not clinicians.What did they find? The rate of people experiencing Major Depressive Disorder (MDD), as defined in DSM-IV, in the past year, was 8.3%. When they examined ethnicity, this ranged from 6.7% in African Americans to 11.8% in Puerto Ricans. The average severity of the depression was roughly the same in all ethnic groups.Of those with MDD, 51% reported that they'd had treatment in the past year, either antidepressants, psychotherapy, or both. This ranged from 53% for Whites down to just 29% of Caribbean Blacks and 33% of Mexican Americans. Therapy was somewhat more popular than drugs in all ethnic groups, although a lot of people used both. However, few of the treatments were classed as "guideline-concordant", i.e. long enough to do any good, which they defined asuse of an antidepressant for at least 60 days with supervision by a psychiatrist, or other prescribing clinician, for at least 4 visits in the past year. For psychotherapy...having at least 4 visits to a mental health professional in the past year lasting on average for at least 30 minutes each.Only 21% of depressed people were getting such treatment, even though these strike me as very lenient guidelines, especially in the case of psychotherapy - how much good is 2 hours per year doing to do?*So depression's undertreated. Too little, for too few. But this rests on an assumption: that we should treat Major Depressive Disorder.That might not seem like an assumption, but assumptions generally don't. It seems like common sense, almost a tautology - it's a disorder, of course we should treat it! Yet it's not so simple. DSM-IV criteria for MDD require you to have 5 or more out of a list of 9 symptoms, including either depressed mood or a loss of interest in activities, lasting at least 2 weeks, and causing significant distress or impairment in social, occupational, or other important areas of functioning.Fair enough. That's quite useful as a way of ensuring that psychiatrists in different countries are talking about the same thing when they talk about depression. But to think that depression is undertreated because only half of people meeting DSM-IV criteria for Major Depressive Disorder are being treated, is to put absolute faith in DSM-IV as a guide to who to treat. This is not what the DSM was meant to be, and there's no evidence it works for that purpose.Is it really true that people with 5 symptoms need help, and those with 4 don't? Why not 6, or all 9? Why 2 weeks - why not 3 weeks, or 3 months? It's not as if there are loads of studies showing that treating people who have 5 symptoms for 2 weeks, and not treating people who don't, is the best strategy. I'm not aware of any such research.This is not to say that any other criteria would be better than DSM-IV as guides to treatment, or that there is anything identifiably wrong with the DSM-IV criteria (although there is evidence that antidepressants are not useful in people with relatively "mild" MDD). The point is that doctors don't strictly apply textbook criteria when diagnosing and treating mental illness; they also use clinical judgement.I don't know any psychiatrist who would prescribe treatment for someone solely on the basis that they met DSM-IV criteria for MDD. They would also want to know about the severity of the symptoms, whether they're related to any stresses or life events, how far they're "out of character" for that individual, etc. In general, they would deploy their training and experience to try to judge whether this person would benefit from treatment. This is why the DSM-IV carries a cautionary statement that "The proper use of these criteria requires specialized clinical training that provides both a body of knowledge and clinical skills."So, it's far from clear that we should be treating everyone who answers interview questions in such a way that they meet DSM-IV criteria for Major Depressive Disorder. That's an assumption.This isn't to say that everyone who needs depression treatment gets it. Sadly, there are many sufferers who would benefit from help and don't get any, or don't get it as early as they should. We need to do more to help such people. In this respect, depression is undertreated, although it's hard to know the extent of the problem. Yet it's quite possible that depression is also overtreated at the same time.H/T Thanks to The Neurocritic for drawing my attention to this paper.Gonzalez, H., Vega, W., Williams, D., Tarraf, W., West, B., & Neighbors, H. (2010). Depression Care in the United States: Too Little for Too Few Archives of General Psychiatry, 67 (1), 37-46 DOI: 10.1001/archgenpsychiatry.2009.168... Read more »
Gonzalez, H., Vega, W., Williams, D., Tarraf, W., West, B., & Neighbors, H. (2010) Depression Care in the United States: Too Little for Too Few. Archives of General Psychiatry, 67(1), 37-46. DOI: 10.1001/archgenpsychiatry.2009.168
- January 30, 2010
- 02:39 PM
- 818 views
Remembering returns brain states to when the actual experience happened
by William Lu in The Quantum Lobe Chronicles
William James, the influential American philosopher and psychologist of the late 1800's argued that remembering events reactivated motor and sensory brain regions involved during the original event. How right he was! Danker and Anderson have written an extensive review of the research literature looking at how this all happens, cleverly titled "The Ghosts of Brain States Past". Here is there abstract from the latest issue of Psychological Bulletin.There is growing evidence that the brain regions involved in encoding an episode are partially reactivated when that episode is later remembered. That is, the process of remembering an episode involves literally returning to the brain state that was present during that episode. This article reviews studies of episodic and associative memory that provide support for the assertion that encoding regions are reactivated during subsequent retrieval. In the first section, studies are reviewed in which neutral stimuli were associated with different modalities of sensory stimuli or different valences of emotional stimuli. When the neutral stimuli were later used as retrieval cues, relevant sensory and emotion processing regions were reactivated. In the second section, studies are reviewed in which participants used different strategies for encoding stimuli. When the stimuli were later retrieved, regions associated with the different encoding strategies were reactivated. Together, these studies demonstrate not only that the encoding experience determines which regions are activated during subsequent retrieval but also that the same regions are activated during encoding and retrieval. In the final section, relevant questions are posed and discussed regarding the reactivation of encoding regions during retrieval.Some interesting points about reactivation to note: 1. reactivation of the visual system occurs at the multi-granular level2. reactivation is stronger during retrieval of more info3. there's a reduction in reactivation when info is falsely remembered 4. reactivation is correlated with subjective reports of remembering (a bit surprising given how fallible our memories often are)The authors conclude by asking whether reactivation of brain states are more or less easily activated when info is more accessible. What about the role of speed and other varying factors? All of these questions, I am sure, will be answered in no time.Danker, J., & Anderson, J. (2010). The ghosts of brain states past: Remembering reactivates the brain regions engaged during encoding. Psychological Bulletin, 136 (1), 87-102 DOI: 10.1037/a0017937... Read more »
Danker, J., & Anderson, J. (2010) The ghosts of brain states past: Remembering reactivates the brain regions engaged during encoding. Psychological Bulletin, 136(1), 87-102. DOI: 10.1037/a0017937
- January 29, 2010
- 03:00 PM
- 658 views
Homology of the habenula in fish and mammals
by Tantalus Prime in Tantalus Prime
The habenula is a highly conserved structure in the vertebrate central nervous system. It doesn't matter if you look at mammals, reptiles, or fish, we all have it. It seems to be a relay center in communication between the forebrain (in mammals) and a whole host of midbrain structures, including the substantia nigra and raphe nuclei. These are the dopaminergic and serotonergic centers of the brain. So, you can understand why some who study addiction, schizophrenia, and/or depression are turning their attention habenularly (and if you don't understand, follow those links). In fact at least one case study points to deep brain stimulation of the lateral habenula as a potential therapy for treatment resistant depression.While all vertebrates have a habenula, they don't all look the same. In addition to showing profound lateralization, the habenula of fish do not seem to separate into medial and lateral nuclei, as they do in mammals. However, just because the gross anatomy is different doesn't mean that connectivity (and function) follows suit. Amo et al. (2010) hypothesized that, because it is such a conserved structure, habenula of the zebrafish would also show subdivisions based on connectivity.This is basically a retrograde/anterograde tracing study. Except instead of using peroxidase based stains they are using awesomely fluorescent compounds. By injecting in the serotonergic centers of the zebrafish, they found retrograde labeling clustered within the ventral habenula; in mammals, similar tracing studies would show labeling in the lateral habenula. It is already known that the zebrafish dorsal habenula (and mammalian medial habenula) sends projections to the interpeduncular nucleus. So it seems that the medial/lateral subdivision in mammals corresponds to a dorsal/ventral subdivision in zebrafish. They also did an anterograde tracer to confirm this connection. Plus, as further confirmation, in mammals the descending projections from the medial habenula form the core of the fasciculus retroflexus while the projections from the lateral habenula form the sheath. Do the projections from the dorsal and ventral habenula of the zebrafish follow such a pattern? I wouldn't be mentioning it if they didn't.The green is GFP expressed in the dorsal habenula neurons while the navy blue is neurobiotin taken up retrogradely by ventral habenular neurons. Neat stuff.So now we know that the habenula of mammals and fish are homologous. Why is this important? One, transgenic studies in mammals are kind of messy. Sure, there is lots of work being done on mice, but the availability of other transgenic mammals is limited. By contrast, zebrafish may offer an alternative means of studying the functionality of habenular output through genetic manipulation (1).Second, by identifying genes specific to the two habenular subdivisions, the authors were able to look at the development of the habenula in zebrafish. Turns out that the fish really do have a medial and lateral subdivision, the lateral division just migrates to a ventral position during development (2). This makes for a nice picture too.Now, if the ventral habenula has glutamatergic projections that inhibit monoaminergic brain centers, that would really be something. Images via The Journal of NeuroscienceAmo, R., Aizawa, H., Takahoko, M., Kobayashi, M., Takahashi, R., Aoki, T., & Okamoto, H. (2010). Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula Journal of Neuroscience, 30 (4), 1566-1574 DOI: 10.1523/JNEUROSCI.3690-09.2010(1) Sorry, drosophila. I know you have a lot to offer, but you must be a vertebrate to go on this ride.(2) I am showing my speciesism, aren't I? It could just as well be that the mammalian ventral habenula fails to migrate to its proper position.Inane ramblings about science, religion, parenting, et al.... Read more »
Amo, R., Aizawa, H., Takahoko, M., Kobayashi, M., Takahashi, R., Aoki, T., & Okamoto, H. (2010) Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula. Journal of Neuroscience, 30(4), 1566-1574. DOI: 10.1523/JNEUROSCI.3690-09.2010
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