30 maart 2009

Amyloid and Tau poster


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Electrophysiology of the Neuron

Neurons are fascinating study objects. The tools to explore this just came in real cheap.

Electrophysiology of the Neuron" is an interactive tutorial that comes with a computer disk for simulation of single neurons on a Macintosh or IBM-PC compatible computer. It was available from Oxford University Press ISBN # 0-19-509167-1 (mac) and 0-19- 509111-6 (PC), and is now out of print. It was designed to be an adjunct to Neurobiology, 3rd edition by Gordon Shepherd, but can also be used as a stand alone text.

26 maart 2009

Zap the Evil PTSD memory

Some years ago Your servant twisted his brain and came up with a scheme to lessen the strength of associative clues to PTSD provoking memory traces. This complex procedure consisted of collecting specific knowledge about the patients PTSD problem, checking out stress levels induced by different associative links by using HRV and GSR measurements and then switching to ERP measurements of specific visual (or auditive) stimuli to find when (and where using Loreta) the sources of the culprit networks would be. The general idea was that when one evokes memories (images, feelings) these memory traces are recalled from their stores and temporarily vulnerable to interfering interventions (fi rTMS) on the re encoding phase of the recall process. Literature in nature Neurosciences had shown this sequence to happen in order of 100-200 msec. Timed by the ERP sources a fast neuronavigated rTMS could zap it at that stage erasing it or probably lessen the associative strenght wich could the be measured (we do EBM over here) by reasseessing the HRV and GSR to cues again. Nice and elegant ? Although the idea looked worth pursuing (in the eye of the beholder) as it would allow specific personalized therapy it was also clear that this would be complex, involving lots of time and resources and would probably be way to costly to be used on a large base. When it became clear that propanolol also weakens the re encoding it the plan became again put on the drawing table. However the solution these authors came up with (in mice) is much better and way more elegant !! A very readable description of the whole strategy whereby CREB expressing neurons (learning neurons) are selectively botoxed out is found in this blog: NEUROTOPIA . A must read. Science 13 March 2009: Vol. 323. no. 5920, pp. 1492 - 1496 DOI: 10.1126/science.1164139 Reports Selective Erasure of a Fear Memory Jin-Hee Han,1,2,3 Steven A. Kushner,1,4 Adelaide P. Yiu,1,2 Hwa-Lin (Liz) Hsiang,1,2 Thorsten Buch,5 Ari Waisman,6 Bruno Bontempi,7 Rachael L. Neve,8 Paul W. Frankland,1,2,3 Sheena A. Josselyn1,2,3* Memories are thought to be encoded by sparsely distributed groups of neurons. However, identifying the precise neurons supporting a given memory (the memory trace) has been a long-standing challenge. We have shown previously that lateral amygdala (LA) neurons with increased cyclic adenosine monophosphate response element–binding protein (CREB) are preferentially activated by fear memory expression, which suggests that they are selectively recruited into the memory trace. We used an inducible diphtheria-toxin strategy to specifically ablate these neurons. Selectively deleting neurons overexpressing CREB (but not a similar portion of random LA neurons) after learning blocked expression of that fear memory. The resulting memory loss was robust and persistent, which suggests that the memory was permanently erased. These results establish a causal link between a specific neuronal subpopulation and memory expression, thereby identifying critical neurons within the memory trace.

22 maart 2009

To program a Shaky robot

programming a shaky robot can be great fun but also provide great insights into the working of human brain motor systems. That is what the people at Riken were trying to do although I am sure they really had fun and enjoyed doing this. read the detailed article here at PLOS ..... Programmers of robots have long been challenged by the difficulty of implementing some of the simplest of human activities, such as walking up stairs or digging a ditch. This is partially due to the versatility of human motor behavior in varying situations. Such robustness can be achieved with a functional hierarchy: a division of labor that allows complex motor behaviors to arise from simpler tasks that are connected at a higher level. Previously, researchers had theorized that a connection of reusable sub-movements called motor primitives would be represented by spatially localized networks in the brain. Now, Yuichi Yamashita and Jun Tani from the RIKEN Brain Science Institute, Wako, have shown that the temporal characteristics of neurons in these motor networks may be just as critical to their functional hierarchy1. Yamashita and Tani took a synthetic approach to test their hypothesis that multiple timescales of activity could mediate motor organization. To this end, the scientists trained a robot to complete a set of distinct, but related, tasks. These motor behaviors included picking up a block to shake it side to side (Fig. 1), picking up a block to shake it up and down, and touching the top of a block with one hand. “It is generally thought that diverse behavior of an animal results from a functional hierarchy of the motor-control system,” explains Yamashita, where “motor primitives are flexibly integrated.” For example, the robot’s tasks could be executed by mixing and matching such primitives as making contact with an object, lifting it, and shaking it. The key distinction in Yamashita and Tani’s work was that the hierarchical organization arose from multiple timescales in the network activity, rather than through spatial connections. The spatially based networks of previous studies consisted of isolated modules responding to each primitive in the lower levels, and gates to select and switch between primitives in the higher levels. By contrast, the neural network of Yamashita and Tani’s robot comprised fast units, which could respond quickly to changing inputs, and slow units, which tended to avoid rapid fluctuations by relying on previous states. Based on the network activity, it appeared that the fast units had spontaneously organized to represent motor primitives, whereas the slow units resembled gates that ordered and activated the primitives. This discovery helps to explain the puzzling discrepancy between previous theories of spatially based motor organization and the elusive evidence of such spatial organization in the animal brain.

I feel the Body Electric

20 maart 2009

18 maart 2009

What could make Lisa happy ?

The complete answer can be found on Cognitive daily (a must visit Blog by Greta and Dave Munger) Hint: the answer is (not) just around the corner.

About Docters Young and Old: Decisions and Drones

Moving my activity from Medical forum mailing list (mainly topics on syndicalism and politics) towards more intensive neuroscience activities, has been a most rewarding strategy for me. Taking some distance and neuroscientific goggled perspective has offered me new and fruitfull insights on human psychology and decision processes. I have not completely left the Medical forum though and will keep lurking a lot of the time but interventions and comments are already sparse although they sometimes keep irritating some syndicalist powers to be. That's a good thing as it stirs the debate. Recently I got fascinated by an animated ongoing discussion about the obligation of docters over 60 to participate in weekend gards. Apart from all arguments large and small that were deployed with great taste of debate and advocacy by many talented collegues I strikes me again how our decision processes are at work without us actors on the stage being fully aware of the underlying processes. In neuroscience we know that decision making networks are very hardwired in the brain. There is the "logical reasoning channel" mostly with network activity converging towards the prefrontal cortex while there is another more "personal and emotional" decision making neuronal highway where superior temporal cortex, gyrus cinguli posterior and frontomedial cortex are involved. Was it not Freud who stated: when reason and emotion are in conflict , emotion often wins. But everybody labels his decision as "rational and logical" what is of course far from painting the complete picture. Both ways are valid as the independent output of different weighting systems. Younger docters who broadcast their pure rationallity (:-) "we are young, we are scientifically sound and we are logical" come up with pure rational and very logical sounding sets of arguments why older docters should continue to help them out doing weekend , while older docters who broadcast their wisdom, experience and rationality (;-) will try to convince the audience why this should not be. How often are we not judged by people who cannot (or refuse) to activate their "empathic system" just to win the debate with unilateral rational logical sounding arguments ?
Every good decision process is characterised by posting the output of both systems side by side "sui generis" and decide by weighted concensus. Clearly not an easy task at all.
To get an idea about the implication of this remote versus close decision process it is good to read the blog of at Frontal Cortex about the "Morality of the Drones". Young docters should know what drones are and older docters who do not should be exempted from weekend gards until their Starwars knowledge base has been updated ;-)
Here a situation is sketched where army personel housed in trailers somewhere in Arizona are steering unmanned (but heavily armed) light aircraft "drones" on information gathering missions (somewhere around the pakistan border) in taliban country and also from time to time "take out" the foes. This is a very mechanical decision: is it an ennemy ? is he/she harmfull or dangerous for our troops (fi preparing a road bom): if yes on all questions.. press button. Bye bye sweet ennemy. Flight goes on. Conscience can easily come to rest knowing prefrontally that one has saved the lives of many innocent soldiers or personel that were targetted by that nasty bom or landmine. So far so good but what would conscience say if one could only reach that same life saving effect (rational) by physically sticking a nife into that TTT (terrible Taliban terrorist). Logically that should make no difference.. should it. In his blog another classical example is given about the railroad tender that gets loose. Read it there . It sure can make You reflect. Ethics are everywhere. Even posted on an innocent medical mail list to be read by young and old, from 7 to 77.
Georges Otte

17 maart 2009

Where did I put My Hippocampus !?

The folks at DANA will be glad to help You out as they are celebrating Brain Awareness Week.

N1 P2 again

Schizophrenia Bulletin Advance Access published online on March 12, 2009 Schizophrenia Bulletin, doi:10.1093/schbul/sbp003

© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Reductions in the N1 and P2 Auditory Event-Related Potentials in First-Hospitalized and Chronic Schizophrenia

Dean F. Salisbury1,2,3, K.C. Collins3 and Robert W. McCarley2,4 2 Department of Psychiatry, Harvard Medical School, Boston, MA 3 Cognitive Neuroscience Laboratory, McLean Hospital, Belmont, MA 4 Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA

1 To whom correspondence should be addressed; Cognitive Neuroscience Laboratory, McLean Hospital, 115 Mill Street NBG21, Belmont, MA 02478; tel: 617-855-3786, fax: 617-855-3795, e-mail: dean_salisbury@hms.harvard.edu.

The N1 auditory event-related potential (ERP) is reduced in chronic schizophrenia, as is the P2 to attended tones. N1 reduction may be endophenotypic for schizophrenia, being reduced in twins of schizophrenic patients and showing heritability. Results in family members, however, are equivocal, with abnormally small N1 (consistent with an endophenotype) and abnormally large N1 (inconsistent with an endophenotype) reported. P2 has been little studied in schizophrenia or family members. One crucial step in establishing endophenotypes is to rule out causal chronicity factors. We examined schizophrenia patients within 1 year of first hospitalization (most within 2 wk), chronically ill patients, and matched controls to examine N1 and P2 reductions and disease stage. Two active target detection oddball tasks were used, one with 97-dB tones against 70-dB white masking noise, the second with 97-dB tones without noise. Results from 8 samples are reported: first-hospitalized patients and matched controls and chronic patients and matched controls for the 2 tasks. N1 and P2 were measured from the standard stimuli. N1 and P2 were significantly reduced in chronic patients, as expected, and reduced in first-hospitalized patients. Because N1 and P2 are reduced even at the first hospitalization for schizophrenia, they may serve as viable electrophysiological endophenotypes for the disorder. However, deficit early in the disease is necessary but not sufficient to establish these ERPs as endophenotypes. Deficits must next be demonstrated in at least a subset of unaffected family members, a crucial criterion for an endophenotype.

Keywords: schizophrenia / first episode / event-related potential / endophenotype / N1 / N100 / P2 / P200

N1 P2 again

Schizophrenia Bulletin Advance Access published online on March 12, 2009 Schizophrenia Bulletin, doi:10.1093/schbul/sbp003

© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Reductions in the N1 and P2 Auditory Event-Related Potentials in First-Hospitalized and Chronic Schizophrenia

Dean F. Salisbury1,2,3, K.C. Collins3 and Robert W. McCarley2,4 2 Department of Psychiatry, Harvard Medical School, Boston, MA 3 Cognitive Neuroscience Laboratory, McLean Hospital, Belmont, MA 4 Boston Veterans Affairs Healthcare System, Brockton Division, Brockton, MA

1 To whom correspondence should be addressed; Cognitive Neuroscience Laboratory, McLean Hospital, 115 Mill Street NBG21, Belmont, MA 02478; tel: 617-855-3786, fax: 617-855-3795, e-mail: dean_salisbury@hms.harvard.edu.

The N1 auditory event-related potential (ERP) is reduced in chronic schizophrenia, as is the P2 to attended tones. N1 reduction may be endophenotypic for schizophrenia, being reduced in twins of schizophrenic patients and showing heritability. Results in family members, however, are equivocal, with abnormally small N1 (consistent with an endophenotype) and abnormally large N1 (inconsistent with an endophenotype) reported. P2 has been little studied in schizophrenia or family members. One crucial step in establishing endophenotypes is to rule out causal chronicity factors. We examined schizophrenia patients within 1 year of first hospitalization (most within 2 wk), chronically ill patients, and matched controls to examine N1 and P2 reductions and disease stage. Two active target detection oddball tasks were used, one with 97-dB tones against 70-dB white masking noise, the second with 97-dB tones without noise. Results from 8 samples are reported: first-hospitalized patients and matched controls and chronic patients and matched controls for the 2 tasks. N1 and P2 were measured from the standard stimuli. N1 and P2 were significantly reduced in chronic patients, as expected, and reduced in first-hospitalized patients. Because N1 and P2 are reduced even at the first hospitalization for schizophrenia, they may serve as viable electrophysiological endophenotypes for the disorder. However, deficit early in the disease is necessary but not sufficient to establish these ERPs as endophenotypes. Deficits must next be demonstrated in at least a subset of unaffected family members, a crucial criterion for an endophenotype.

Keywords: schizophrenia / first episode / event-related potential / endophenotype / N1 / N100 / P2 / P200

mediotemporal theta

Image that mediotemporal theta indicates a brain state in wich remembering will be succesfull. it works as a predictor for succesfull recall. It was done with magnetoEEG but qEEG high density should also do the trick. fascinating... my dear dr Spock. It is indeed between Your ears.

Citation: "Medial temporal theta state before an event predicts episodic encoding success in humans." By Sebastian Guderian, Bjorn H. Schott, Alan Richardson-Klavehn and Emrah Duzel. Proceedings of the National Academy of Sciences, Vol. 106, No. 11, March 16, 2009.

16 maart 2009

Free medical journals

Some of the best things come free.

Dynamic Causal Modelling

Granger and Friston.

Brainbuilders Inc

These people are building tomorrows (European) brain. There seems to be a large scale endeavor on this as also DARPA and the China Brain project (Hugo de garis) are competing on this track.

Neuronavigated rTMS

A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression

Paul B Fitzgerald1, Kate Hoy1, Susan McQueen1, Jerome J Maller1, Sally Herring1, Rebecca Segrave1, Michael Bailey2, Greg Been1, Jayashri Kulkarni1 and Zafiris J Daskalakis3

  1. 1Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd Melbourne, Victoria, Australia
  2. 2Monash University Department of Epidemiology and Preventive Medicine, The Alfred Hospital, Commercial Rd Melbourne, Victoria, Australia
  3. 3Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

Correspondence: Professor PB Fitzgerald, Alfred Psychiatry Research Centre, First Floor, Old Baker Building, The Alfred, Commercial Rd Melbourne, Victoria 3004, Australia. Tel: +61 3 9076 6552; Fax: +61 3 9076 6588; E-mail: paul.fitzgerald@med.monash.edu.au

Received 8 August 2008; Revised 14 December 2008; Accepted 16 December 2008; Published online 14 January 2009.

Top

Abstract

The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subject's MRI scan. There was an overall significant reduction in the Montgomery–Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.

Keywords:

repetitive transcranial magnetic stimulation, depression, prefrontal cortex, respons

Brain Imaging free

A generous offer from Springer. Free online to end of April.

Brain Imaging free

A generous offer from Springer. Free online to end of April.

The challenge !! Remember ?

The challenge: Break the code. The cues and hints:

Clue 1: The code is read from left to right, beginning with the upper leftmost corner.

Clue 2: Colors from similar spectral families are considered to be the same (example: pink is equal to red)

Clue 3: It is a triplet code

Clue 4: The only spectral families that code (alone or in combination) for actual letters are yellow, green and red.

Clue 5: The dots on the bottom line of MicroArray code for blanks.

Clue 6: The answer is a statement having six words and the following letters are not used: J, K, L, M, P, Q, R, U, V, X, Y, Z.

Clue 7: In the triplet code, three adjacent dots code for each letter, which should be placed at the site of the center dot. Words are created from abutting triplet-coded letters. The code for the letter 'e' is 'yellow green green' and the code for the letter 'n' is 'green red green'.

The solution: read here

The winners: -->

14 maart 2009

Lucy in the Sky: Smile back !

Audiocubes

First we had Ice cubes, then light cubes but now there the amazing audio cubes. Check this out ! It can awake the "Regi" in you.

Pi day

14 th march 2009: rearrange as 3/14/09 this is .... YEP !!! 3,1409.... Pi !!! Celebrate Pi day. You can only eat PI -za or PI - ta but You are allowed to add some Pi-ments. Pi can help You to become a become math Pi-onnier or a Pi-lot... so keep going.... PS You know when is Eulers "e" day ? Answer: (the day after D day) sorry.........bad joke !! Pi-ty this.

Friston Website

A very interesting website stuffed with lots on interesting presentations and articles. Big Kudo's to Dr. Luc R. for signaling this one.

13 maart 2009

Walk my World

A new VR device creates complete freedom of movement in any VR world. Ideal for rehab and exploring strange new worlds and boldly go where no man has gone before....

fMRI: Where am I ?

Mind reading no longer mind boggling.....

11 maart 2009

Was Kloos correct ?

IK BEN EEN GOD

Ik ben een God in 't diepst van mijn gedachten, En zit in 't binnenst van mijn ziel ten troon Over mij zelf en 't al, naar rijksgeboôn Van eigen strijd en zege, uit eigen krachten. Now take an MRI machine, a set of believers versus non-believers and 60 questions to see where in the brain Kloos was alluding on. Not so clear cut as the poet might have thought... ResearchBlogging.orgD. Kapogiannis, A. K. Barbey, M. Su, G. Zamboni, F. Krueger, J. Grafman (2009). Cognitive and neural foundations of religious belief Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0811717106

Cool stuff from Media lab (look at the watch)

10 maart 2009

09 maart 2009

On neurodegeneration

Amyloid 42 fibrils

6 March 2009. The Aβ42 peptide may self-aggregate to form fibers with a structure profoundly different from those made of its less pathogenic cousin Aβ40. So suggests a cryoelectron microscopy (cryoEM) study—the first reported for Aβ1-42—in this week’s PNAS Early Edition. In contrast to structural studies of Aβ1-40 that have predicted a tight arrangement of protofilaments in mature fibers, the new model describes Aβ1-42 fibers as pairs of loosely connected protofilaments snaked around a hollow core. “There might be a weak link in this seemingly impenetrable molecule,” said neurologist Jin-Moo Lee of Washington University School of Medicine, St. Louis, Missouri, who led the new research. If fibrillar Aβ42 “is in fact a toxic species, then this is a potential site where we might disrupt the fibril,” Lee said. The authors and other scientists caution, though, that differences in growth conditions for the various Aβ species make it hard to directly compare structural studies of Aβ1-40 and Aβ1-42. The relevance of synthetic Aβ fibril structures—the kind used here—to Alzheimer disease also remains to be seen.

Architecture of the brain

CC: Cognitive Control

memory and learning

Do not Fear !

Personal Robots @ MIT

Artificial Biology

discover a new world at MIT World

08 maart 2009

eating disorders and sleep

NES or SRED ? : read a nice overview article here.

Eternal Classic: Hotel California

Depression and escitalopram

An article the lancet with study objective and architecture from Cochrane foundation. Clearly in favor of escitalopram. The recurrent story that S enantiomers of citalopram are only a marketing trick (conspiration theory) are clearly proven false mémé's both in basic research and clinical studies. escitalopram (the S enantiomer) is 30 times more potent then R citalopram that hunders the effect of the S enantiomer at the serotonine reuptake receptor. beste quality and less side effects for our patients are better provided by the S enantiomer (escitalopram). This is the way to go in a condition suc as depression that needs the best of treatments.
The Lancet, Volume 373, Issue 9665, Pages 746 - 758, 28 February 2009
doi:10.1016/S0140-6736(09)60046-5Cite or Link Using DOI
Editors' note: Depression is a major cause of disability worldwide, and the need for treatment options, whether they be antidepressant drugs or psychological interventions, is correspondingly great. A range of clinically-proven antidepressants is available, and this multiple treatments meta-analysis seeks to draw conclusions from the many randomised trials in which drugs have been studied against active comparators. Weighing systematically the evidence available on both efficacy and tolerability, the authors suggest that sertraline and escitalopram might be appropriate first-choice treatments.

Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis