Wednesday, March 10, 2010

Can We Rely on fMRI?

Craig Bennett (of Prefrontal.org) and Michael Miller, of dead fish brain scan fame, have a new paper out: How reliable are the results from functional magnetic resonance imaging?


Tal over at the [citation needed] blog has an excellent in-depth discussion of the paper, and Mind Hacks has a good summary, but here's my take on what it all means in practical terms.

Suppose you scan someone's brain while they're looking at a picture of a cat. You find that certain parts of their brain are activated to a certain degree by looking at the cat, compared to when they're just lying there with no picture. You happily publish your results as showing The Neural Correlates of Cat Perception.

If you then scanned that person again while they were looking at the same cat, you'd presumably hope that exact same parts of the brain would light up to the same degree as they did the first time. After all, you claim to have found The Neural Correlates of Cat Perception, not just any old random junk.

If you did find a perfect overlap in the area and the degree of activation that would be an example of 100% test-retest reliability. In their paper, Bennett and Miller review the evidence on the test-retest reliability of fMRI studies. They found 63 of them. On average, they found that the reliability of fMRI falls quite far short of perfection: the areas activated (clusters) had a mean Dice overlap of 0.476, while the strength of activation was correlated with a mean ICC of 0.50.

But those numbers, taken out of context, do not mean very much. Indeed, what is a Dice overlap? You'll have to read the whole paper to find out, but even when you do, they still don't mean that much. I suspect this is why Bennett and Miller don't mention them in the Abstract of the paper, and in fact they don't spend more than a few lines discussing them at all.

A Dice overlap of 0.476 and an ICC of 0.50 are what you get if average over all of the studies that anyone's done looking at the test-retest reliability of any particular fMRI experiment. But different fMRI experiments have different reliabilities. Saying that the average reliability of fMRI is 0.5 is rather like saying that the mean velocity of a human being is 0.3 km per hour. That's probably about right, averaging over everyone in the world, including those who are asleep in bed and those who are flying on airplanes - but it's not very useful. Some people are moving faster than others, and some scans are more reliable than others.


Most of this paper is not concerned with "how reliable fMRI is", but rather, with how to make any given scanning experiment more reliable. And this is an important thing to write about, because even the most optimistic cognitive neuroscientist would agree that many fMRI results are not especially reliable, and as Bennett and Miller say, reliability matters for lots of reasons:
Scientific truth. While it is a simple statement that can be taken straight out of an undergraduate research methods course, an important point must be made about reliability in research studies: it is the foundation on which scientific knowledge is based. Without reliable, reproducible results no study can effectively contribute to scientific knowledge.... if a researcher obtains a different set of results today than they did yesterday, what has really been discovered?
Clinical and Diagnostic Applications. The longitudinal assessment of changes in regional brain activity is becoming increasingly important for the diagnosis and treatment of clinical disorders...
Evidentiary Applications. The results from functional imaging are increasingly being submitted as evidence into the United States legal system...
Scientific Collaboration. A final pragmatic dimension of fMRI reliability is the ability to share data between researchers...
So what determines the reliability of any given fMRI study? Lots of things. Some of them are inherent to the nature of the brain, and are not really things we can change: activation in response to basic perceptual and motor tasks is probably always going to be more reliable than activation related to "higher" functions like emotions.

But there are lots of things we can change. Although it's rarely obvious from the final results, researchers make dozens of choices when designing and analyzing an fMRI experiment, many of which can at least potentially have a big impact on the reliability of their findings. Bennett and Miller cover lots of them:
voxel size... repetition time (TR), echo time (TE), bandwidth, slice gap, and k-space trajectory... spatial realignment of the EPI data can have a dramatic effect on lowering movement-related variance ... Recent algorithms can also help remove remaining signal variability due to magnetic susceptibility induced by movement... simply increasing the number of fMRI runs improved the reliability of their results from ICC = 0.26 to ICC = 0.58. That is quite a large jump for an additional ten or fifteen minutes of scanning...
The details get extremely technical, but then, when you do an fMRI scan you're using a superconducting magnet to image human neural activity by measuring the quantum spin properties of protons. It doesn't get much more technical.

Perhaps the central problem with modern neuroimaging research is that it's all too easy for researchers to write off the important experimental design issues as "merely" technicalities, and just put some people in a scanner using the default scan sequence and see what happens. This is something few fMRI users are entirely innocent of, and I'm certainly not, but it is a serious problem. As Bennett and Miller point out, the devil is in the technical details.
The generation of highly reliable results requires that sources of error be minimized across a wide array of factors. An issue within any single factor can significantly reduce reliability. Problems with the scanner, a poorly designed task, or an improper analysis method could each be extremely detrimental. Conversely, elimination of all such issues is necessary for high reliability. A well maintained scanner, well designed tasks, and effective analysis techniques are all prerequisites for reliable results.
ResearchBlogging.orgBennett CM, Miller MB. (2010). How reliable are the results from functional magnetic resonance imaging? Annals of the New York Academy of Sciences

Can We Rely on fMRI?

Craig Bennett (of Prefrontal.org) and Michael Miller, of dead fish brain scan fame, have a new paper out: How reliable are the results from functional magnetic resonance imaging?


Tal over at the [citation needed] blog has an excellent in-depth discussion of the paper, and Mind Hacks has a good summary, but here's my take on what it all means in practical terms.

Suppose you scan someone's brain while they're looking at a picture of a cat. You find that certain parts of their brain are activated to a certain degree by looking at the cat, compared to when they're just lying there with no picture. You happily publish your results as showing The Neural Correlates of Cat Perception.

If you then scanned that person again while they were looking at the same cat, you'd presumably hope that exact same parts of the brain would light up to the same degree as they did the first time. After all, you claim to have found The Neural Correlates of Cat Perception, not just any old random junk.

If you did find a perfect overlap in the area and the degree of activation that would be an example of 100% test-retest reliability. In their paper, Bennett and Miller review the evidence on the test-retest reliability of fMRI studies. They found 63 of them. On average, they found that the reliability of fMRI falls quite far short of perfection: the areas activated (clusters) had a mean Dice overlap of 0.476, while the strength of activation was correlated with a mean ICC of 0.50.

But those numbers, taken out of context, do not mean very much. Indeed, what is a Dice overlap? You'll have to read the whole paper to find out, but even when you do, they still don't mean that much. I suspect this is why Bennett and Miller don't mention them in the Abstract of the paper, and in fact they don't spend more than a few lines discussing them at all.

A Dice overlap of 0.476 and an ICC of 0.50 are what you get if average over all of the studies that anyone's done looking at the test-retest reliability of any particular fMRI experiment. But different fMRI experiments have different reliabilities. Saying that the average reliability of fMRI is 0.5 is rather like saying that the mean velocity of a human being is 0.3 km per hour. That's probably about right, averaging over everyone in the world, including those who are asleep in bed and those who are flying on airplanes - but it's not very useful. Some people are moving faster than others, and some scans are more reliable than others.


Most of this paper is not concerned with "how reliable fMRI is", but rather, with how to make any given scanning experiment more reliable. And this is an important thing to write about, because even the most optimistic cognitive neuroscientist would agree that many fMRI results are not especially reliable, and as Bennett and Miller say, reliability matters for lots of reasons:
Scientific truth. While it is a simple statement that can be taken straight out of an undergraduate research methods course, an important point must be made about reliability in research studies: it is the foundation on which scientific knowledge is based. Without reliable, reproducible results no study can effectively contribute to scientific knowledge.... if a researcher obtains a different set of results today than they did yesterday, what has really been discovered?
Clinical and Diagnostic Applications. The longitudinal assessment of changes in regional brain activity is becoming increasingly important for the diagnosis and treatment of clinical disorders...
Evidentiary Applications. The results from functional imaging are increasingly being submitted as evidence into the United States legal system...
Scientific Collaboration. A final pragmatic dimension of fMRI reliability is the ability to share data between researchers...
So what determines the reliability of any given fMRI study? Lots of things. Some of them are inherent to the nature of the brain, and are not really things we can change: activation in response to basic perceptual and motor tasks is probably always going to be more reliable than activation related to "higher" functions like emotions.

But there are lots of things we can change. Although it's rarely obvious from the final results, researchers make dozens of choices when designing and analyzing an fMRI experiment, many of which can at least potentially have a big impact on the reliability of their findings. Bennett and Miller cover lots of them:
voxel size... repetition time (TR), echo time (TE), bandwidth, slice gap, and k-space trajectory... spatial realignment of the EPI data can have a dramatic effect on lowering movement-related variance ... Recent algorithms can also help remove remaining signal variability due to magnetic susceptibility induced by movement... simply increasing the number of fMRI runs improved the reliability of their results from ICC = 0.26 to ICC = 0.58. That is quite a large jump for an additional ten or fifteen minutes of scanning...
The details get extremely technical, but then, when you do an fMRI scan you're using a superconducting magnet to image human neural activity by measuring the quantum spin properties of protons. It doesn't get much more technical.

Perhaps the central problem with modern neuroimaging research is that it's all too easy for researchers to write off the important experimental design issues as "merely" technicalities, and just put some people in a scanner using the default scan sequence and see what happens. This is something few fMRI users are entirely innocent of, and I'm certainly not, but it is a serious problem. As Bennett and Miller point out, the devil is in the technical details.
The generation of highly reliable results requires that sources of error be minimized across a wide array of factors. An issue within any single factor can significantly reduce reliability. Problems with the scanner, a poorly designed task, or an improper analysis method could each be extremely detrimental. Conversely, elimination of all such issues is necessary for high reliability. A well maintained scanner, well designed tasks, and effective analysis techniques are all prerequisites for reliable results.
ResearchBlogging.orgBennett CM, Miller MB. (2010). How reliable are the results from functional magnetic resonance imaging? Annals of the New York Academy of Sciences

Tuesday, March 9, 2010

Alabama Drivers License Birthday Cakes

courses to be held in Buenos Aires, very useful! ...

TCC INTENSIVE IN AUTISM AND PDD:

date: Wednesday March 17, 2010
Hours: 18-21 hours
Place: National Technological University
Address: Medrano 951, 2 nd floor, phone: 4867-7545

Course Description:

Intensive cognitive behavioral therapy in autism and PDD. Doctor charges of psychology at the UBA. Eduardo Cossi. 5 meetings of 18 to 22 hours, five consecutive Thursdays. Incio Thursday 18 March. Quotas limited. Certified

UTN. UTN Reports

capital Medrano 951 (2nd floor-extension) 48677545. PRE-REGISTRATION

acomp_terapeutico@yahoo.com.ar


YEAR COURSE OF THERAPEUTIC SUPPORT

date: Wednesday March 17, 2010
Hours: 10 am
Place: National Technological University
Address: Medrano 951, 2 nd floor, phone: 4867-7545

Course Description:

NATIONAL TECHNOLOGICAL UNIVERSITY COURSE

therapeutic support.

Module I. initiation and module ii. expertise and practices.
Start: Wednesday 17 March, 10 to 12 hours.

Duration 27 weekly meetings.

Objectives: To train an auxiliary therapeutic
able to collaborate and participate in various professional teams in attendance, with strong theoretical and practical tools in a framework defined by the figure of a qualified employee health care, education and field community partner.
Aimed at students, professionals, auxiliary health workers, education, the social community and general assistance, family members of patients and the general community.

APPROVAL CERTIFICATE IS PROVIDED.

National Technological University. BUENOS AIRES FACULTAD REGIONAL
.
Ministry of Culture and University Extension.

Topics: History and Definition
technique of therapeutic support.
concern and basic skills and specific. Delineating the role
Tools and Basics.
Link-Transfer-Monitoring. Organization of work and decision making
's and early clinical intervention.
Dependencies, psychotic disorders, mood disorders, disorders of childhood onset, Third age. Characterization
diagnostic and organizational principles of treatment and intervention of AT.
devices, protocols, consensus. Delimitation
judicial and legal. Ethical principles.
Patient Rights. Legal framework and legal ethics Therapeutic accompaniment (ethics). Disclaimer
.
care and intervention techniques.
social and communication skills.
Troubleshooting and strategies for decision making.
impulse control, anxiety and stress.
cognitive behavioral interventions. System. SPS.
observation and recording.


teaching team: Dr. Eduardo Cossi

. PhD in psychology. UBA. UBACyT researcher. Ms. Veronica

ecossi@psi.uba.ar Recchia. Degree in psychology. UBA. Coordinator.
veronicarecchia@yahoo.com.ar
Space is limited. Pre

by mail: send acomp_terapeutico@yahoo.com.ar full name. ID, contact numbers and e-mail. Medrano

951 2nd floor: University Extension Office. Federal Capital you 48677545.
info@sceu.frba.utn.edu.ar

hope will be useful ...!



MULHER...

ENCONTREI ESTE TEXO NO BLOG SEXTO SENTIDO, DA AMIGA MAYSHAY-http://mayshay.blogspot.com/ E ACHEI LEGAL..

8 de Março - Dia Internacional da Mulher





Origem do Dia Internacional da Mulher

O dia 8 de Março é, desde 1975, comemorado pelas Nações Unidas como Dia Internacional da Mulher
Neste dia, do ano de 1857, as operárias têxteis de uma fábrica de Nova Iorque entraram em greve ocupando a fábrica, para reivindicarem a redução de um horário de mais de 16 horas por dia para 10 horas. Estas operárias, que recebiam menos de um terço do salário dos homens, foram fechadas na fábrica onde, entretanto, se declarara um incêndio, e cerca de 130 mulheres morreram queimadas.
Em 1903, profissionais liberais norte-americanas criaram a Women's Trade Union League. Esta associação tinha como principal objectivo ajudar todas as trabalhadoras a exigirem melhores condições de trabalho.
Em 1908, mais de 14 mil mulheres marcharam nas ruas de Nova Iorque: reivindicaram o mesmo que as operárias no ano de 1857, bem como o direito de voto.
Caminhavam com o slogan "Pão e Rosas", em que o pão simbolizava a estabilidade económica e as rosas uma melhor qualidade de vida.
Em 1910, numa conferência internacional de mulheres realizada na Dinamarca, foi decidido, em homenagem àquelas mulheres, comemorar o 8 de Março como "Dia Internacional da Mulher".








Mulheres
Elas sorriem quando querem gritar.
Elas cantam quando querem chorar.
Elas choram quando estão felizes.
E riem quando estão nervosas.
Elas brigam por aquilo que acreditam.
Elas levantam-se para injustiça.
Elas não levam "não" como resposta quando acreditam que existe melhor solução.
Elas andam sem novos sapatos para suas crianças poderem tê-los.
Elas vão ao medico com uma amiga assustada.
Elas amam incondicionalmente.
Elas choram quando suas crianças adoecem e se alegram quando suas crianças ganham prémios.
Elas ficam contentes quando ouvem sobre um aniversario ou um novo casamento.

Pablo Neruda
OBRIGADA AMIGA



Blog Coletivo-Uma Interação de Amigos- A VIDA FICA MELHOR QUANDO...

Meus Mimos-



SANDRA

NAÕ ESQUEÇA DE LEVAR SEU SELINHO MULHER..AO LADO- ACIMA NA BARRA.


Monday, March 8, 2010

Life Without Serotonin

Via Dormivigilia, I came across a fascinating paper about a man who suffered from a severe lack of monoamine neurotransmitters (dopamine, serotonin etc.) as a result of a genetic mutation: Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin


Neuroskeptic readers will be familiar with monoamines. They're psychiatrists' favourite neurotransmitters, and are hence very popular amongst psych drug manufacturers. In particular, it's widely believed that serotonin is the brain's "happy chemical" and that clinical depression is caused by low serotonin while antidepressants work by boosting it.

Critics charge that there is no evidence for any of this. My own opinion is that it's complicated, but that while there's certainly no simple relation between serotonin, antidepressants and mood, they are linked in some way. It's all rather mysterious, but then, the functions of serotonin in general are; despite 50 years of research, it's probably the least understood neurotransmitter.

The new paper adds to the mystery, but also provides some important new data. Leu-Semenescu et al report on the case of a 28 year old man, with consanguineous parents, who suffers from a rare genetic disorder, sepiapterin reductase deficiency (SRD). SRD patients lack an enzyme which is involved, indirectly, in the production of the monoamines serotonin and dopamine, and also melatonin and noradrenaline which are produced from these two. SRD causes a severe (but not total) deficiency of these neurotransmitters.

The most obvious symptoms of SRD are related to the lack of dopamine, and include poor coordination and weakness, very similar to Parkinson's Disease. An interesting feature of SRD is that these symptoms are mild in the morning, worsen during the day, and improve with sleep. Such diurnal variation is also a hallmark of severe depression, although in depression it's usually the other way around (better in the evening).

The patient reported on in this paper suffered Parkinsonian symptoms from birth, until he was diagnosed with dystonia at age 5 and started on L-dopa to boost his dopamine levels. This immediately and dramatically reversed the problems.

But his serotonin synthesis was still impaired, although doctors didn't realize this until age 27. As a result, Leu-Semenescu et al say, he suffered from a range of other, non-dopamine-related symptoms. These included increased appetite - he ate constantly, and was moderately obese - mild cognitive impairment, and disrupted sleep:
The patient reported sleep problems since childhood. He would sleep 1 or 2 times every day since childhood and was awake during more than 2 hours most nights since adolescence. At the time of the first interview, the night sleep was irregular with a sleep onset at 22:00 and offset between 02:00 and 03:00. He often needed 1 or 2 spontaneous, long (2- to 5-h) naps during the daytime.
After doctors did a genetic test and diagnosed SRD, they treated him with 5HTP, a precursor to serotonin. The patient's sleep cycle immediately normalized, his appetite was reduced and his concentration and cognitive function improved (although that may have been because he was less tired). Here's his before and after hypnogram:

Disruptions in sleep cycle and appetite are likewise common in clinical depression. The direction of the changes in depression varies: loss of appetite is common in the most severe "melancholic" depression, while increased appetite is seen in many other people.

For sleep, both daytime sleepiness and night-time insomnia, especially waking up too early, can occur in depression. The most interesting parallel here is that people with depression often show a faster onset of REM (dreaming) sleep, which was also seen in this patient before 5HTP treatment. However, it's not clear what was due to serotonin and what was due to melatonin because melatonin is known to regulate sleep.

Overall, though, the biggest finding here was a non-finding: this patient wasn't depressed, despite having much reduced serotonin levels. This is further evidence that serotonin isn't the "happy chemical" in any simple sense.

On the other hand, the similarities between his symptoms and some of the symptoms of depression suggest that serotonin is doing something in that disorder. This fits with existing evidence from tryptophan depletion studies showing that low serotonin doesn't cause depression in most people, but does re-activate symptoms in people with a history of the disease. As I said, it's complicated...

ResearchBlogging.orgSmaranda Leu-Semenescu et al. (2010). Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin Sleep, 33 (03), 307-314

Life Without Serotonin

Via Dormivigilia, I came across a fascinating paper about a man who suffered from a severe lack of monoamine neurotransmitters (dopamine, serotonin etc.) as a result of a genetic mutation: Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin


Neuroskeptic readers will be familiar with monoamines. They're psychiatrists' favourite neurotransmitters, and are hence very popular amongst psych drug manufacturers. In particular, it's widely believed that serotonin is the brain's "happy chemical" and that clinical depression is caused by low serotonin while antidepressants work by boosting it.

Critics charge that there is no evidence for any of this. My own opinion is that it's complicated, but that while there's certainly no simple relation between serotonin, antidepressants and mood, they are linked in some way. It's all rather mysterious, but then, the functions of serotonin in general are; despite 50 years of research, it's probably the least understood neurotransmitter.

The new paper adds to the mystery, but also provides some important new data. Leu-Semenescu et al report on the case of a 28 year old man, with consanguineous parents, who suffers from a rare genetic disorder, sepiapterin reductase deficiency (SRD). SRD patients lack an enzyme which is involved, indirectly, in the production of the monoamines serotonin and dopamine, and also melatonin and noradrenaline which are produced from these two. SRD causes a severe (but not total) deficiency of these neurotransmitters.

The most obvious symptoms of SRD are related to the lack of dopamine, and include poor coordination and weakness, very similar to Parkinson's Disease. An interesting feature of SRD is that these symptoms are mild in the morning, worsen during the day, and improve with sleep. Such diurnal variation is also a hallmark of severe depression, although in depression it's usually the other way around (better in the evening).

The patient reported on in this paper suffered Parkinsonian symptoms from birth, until he was diagnosed with dystonia at age 5 and started on L-dopa to boost his dopamine levels. This immediately and dramatically reversed the problems.

But his serotonin synthesis was still impaired, although doctors didn't realize this until age 27. As a result, Leu-Semenescu et al say, he suffered from a range of other, non-dopamine-related symptoms. These included increased appetite - he ate constantly, and was moderately obese - mild cognitive impairment, and disrupted sleep:
The patient reported sleep problems since childhood. He would sleep 1 or 2 times every day since childhood and was awake during more than 2 hours most nights since adolescence. At the time of the first interview, the night sleep was irregular with a sleep onset at 22:00 and offset between 02:00 and 03:00. He often needed 1 or 2 spontaneous, long (2- to 5-h) naps during the daytime.
After doctors did a genetic test and diagnosed SRD, they treated him with 5HTP, a precursor to serotonin. The patient's sleep cycle immediately normalized, his appetite was reduced and his concentration and cognitive function improved (although that may have been because he was less tired). Here's his before and after hypnogram:

Disruptions in sleep cycle and appetite are likewise common in clinical depression. The direction of the changes in depression varies: loss of appetite is common in the most severe "melancholic" depression, while increased appetite is seen in many other people.

For sleep, both daytime sleepiness and night-time insomnia, especially waking up too early, can occur in depression. The most interesting parallel here is that people with depression often show a faster onset of REM (dreaming) sleep, which was also seen in this patient before 5HTP treatment. However, it's not clear what was due to serotonin and what was due to melatonin because melatonin is known to regulate sleep.

Overall, though, the biggest finding here was a non-finding: this patient wasn't depressed, despite having much reduced serotonin levels. This is further evidence that serotonin isn't the "happy chemical" in any simple sense.

On the other hand, the similarities between his symptoms and some of the symptoms of depression suggest that serotonin is doing something in that disorder. This fits with existing evidence from tryptophan depletion studies showing that low serotonin doesn't cause depression in most people, but does re-activate symptoms in people with a history of the disease. As I said, it's complicated...

ResearchBlogging.orgSmaranda Leu-Semenescu et al. (2010). Sleep and Rhythm Consequences of a Genetically Induced Loss of Serotonin Sleep, 33 (03), 307-314

Female Like Penis Piercing

HAPPY WOMEN'S DAY!! Pending pics


Bloggers OF ALL MY FRIENDS ... A VERY HAPPY DAY!! HAPPY

DAY FOR YOU TO THINK ABOUT WOMEN IN WORDS: GREAT FRIENDS, GREAT MOTHERS FIGHTING ETERNAL, BRAVE, SOLIDARITY, kindness and a big heart.
WOMEN WHO ARE ABLE TO GIVE EVERYTHING TO SEE YOUR OWN HAPPY LIFE FOR YOUR CHILDREN HELP TO FORWARD BY DAY AFTER DAY ... WOMEN
admired and emotions with SIMPLE THINGS EVERY DAY WITH THE THINGS THAT ARE OTHER WOMEN FOR SMALL AND NO SENSE. WHY WE TEACH OUR CHILDREN TO THEM AND WONDERS TO FEEL THAT WE PLAY THE SKY WITH HANDS WHEN THINGS GET SEE WHY pray EVERY NIGHT WITH ALL OUR STRENGTH AND FAITH, HOPE TO SEE YOU ACHIEVE FULL. THANKS


BY GIVING YOUR FRIENDSHIP IN THIS WAY WE TOUCHED TRANSIT.



THE MUCH LOVE!!