Tag Archives: Functional MRI

Spot the flaw

Mathematical talent varies widely. It was a humbling thing a few years ago to sit in an upper level college math class on Abstract Algebra with a 16 year old high school student taking the course, listening with one ear while he did his German homework. He was later a double summa in both math and physics at Yale. So do mathematicians think differently? A fascinating paper implies that they use different parts of their brain doing math than when not doing it. The paper has one methodological flaw — see if you can find it.

[ Proc. Natl. Acad. Sci. vol. 113 pp. 4887 – 4889, 4909 – 4917 ’16 ] 15 expert mathematicians and 15 nonMathematicians with comparable academic qualifications were studied (3 literature, 3 history 1 philosophy 2 linguistics, 1 antiquity, 3 graphic arts and theater 1 communcation, 1 heritage conservation — fortunately no feminist studies). They had to listen to mathematical and nonMathematical statements and decide true false or meaningless. The nonMathematical statements referred to general knowledge of nature and history. All this while they were embedded in a Magnetic Resonance Imager, so that functional MRI (fMRI) could be performed.

In mathematicians there was no overlap of the math responsive network (e.g. the areas of the brain activated by doing math) with the areas activated by sentence comprehension and general semantic knowledge.

The same brain networks were activated by all types of mathematical statement (geometry, analysis, algebra and topology) as opposed to nonMathematical statement. The areas activated were the dorsal parietal, ventrolateral temporal and bilateral frontal. This was only present in the expert mathematicians (and only to mathematical statements) These areas are outside those associated with language (inferior frontal gyrus of the left hemisphere). The activated areas are also involved in visual processing of arabic numbers and simple calculation. The activated areas in mathematicians were NOT those related to language or general knowledge.

So what’s wrong with the conclusion? The editorialist (pp. 4887 – 4889) pointed this out but I thought of it independently.

All you can say is that experts working in their field of expertise use different parts of their brain than they use for general knowledge. The nonMathematicians should have been tested in their field of expertise. Shouldn’t be hard to do.

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Why some of us gamble

If you are one of the hapless schlubs who bought a Powerball ticket or two and didn’t win (like me), modern neuroscience can tell you why (but not without a bit of pompous terminology). They call a small chance of winning large amounts — e.g. Powerball along with a large chance of losing a little a positively skewed gamble. Impressed? I’m not.

Nonetheless [ Neuron vol. 89 pp. 63 – 69 ’16 ] is a very interesting paper. Functional Magnetic Resonance Imaging (fMRI – https://en.wikipedia.org/wiki/Functional_magnetic_resonance_imaging) has shown that increased blood flow in one area of the brain (the nucleus accumbent sept) predicts risk seeking choices, while increased blood flow in another (the anterior insula) predicts aversion to risk. The unproven assumption behind fMRI is that increased blood flow is due to increased neural activity.

The neurochemistry of the two regions is quite different. The accumbens gets dopamine input while the insula gets norepinephrine projections.

BTW the insula is unique to man. Our cortex has grown so much (particularly in the frontal region) that it folds over on itself burying the insular cortex — https://en.wikipedia.org/wiki/Insular_cortex.

We are now actually able to measure axon bundles (white matter fiber tracts) in the living brain, using something called diffusion weighted MRI. By and large, fiber tracts tend to have the fibers parallel and running in the same direction. It is far easier for water to flow along parallel fibers than across them, and this is what the technique measures. For the mathematically inclined, what is actually measured is a tensor field, because at any given point in the brain it varies in direction, unlike a vector field which points just one way at a given point (the mathematically inclined know that this is a simplification because vectors are actually a type of tensor).

At any rate, the work used diffusion wieghted MRI to study the white matter tracts connecting the two areas. The larger the tract between insula and accumbens was the more risk averse an individual was. The implication being that a larger tract is a better connection between the two. So your nucleus is your impulsive child and the anterior insula is your mother telling you not to do anything crazy.

Fascinating, but like all this stuff it needs to be replicated, as it probably confirms the original idea for the study.

A huge amount of work will need to be redone

The previous post is reprinted below the —- if you haven’t read it, you should do so now before proceeding.

Briefly, no one had ever bothered to check if subjects were asleep while studying the default mode of brain activity. The paper discussed in the previous post appeared in the 7 May ’14 issue of Neuron.

In the 13 May ’14 issue of PNAS [ Proc. Natl. Acad. Sci. vol. 111 pp. E2066 – E2075 ’14 ] a paper appeared on genetic links to default mode abnormalities in schizophrenia and bipolar disorder.

From the abstract “Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 Schizophrenic probands, 300 psychotic bipolar disorder probands, 179 unaffected first-degree relatives of schizophrenic pro bans, and 206 unaffected first-degree relatives of psychotic bipolar disorder probands to identify default mode networks and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging–genetic relationships. ICA identified three default mode networks.” The paper represents a tremendous amount of work (and expense).

No psychiatric disorder known to man has normal sleep. The abnormalities found in the PNAS study may not be of the default mode network, but in the way these people are sleeping. So this huge amount of work needs to be repeated. An tghis is just one paper. As mentioned a Google search on Default Networks garnered 32,000,000 hits.

Very sad.

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How badly are thy researchers, O default mode network

If you Google “default mode network” you get 32 million hits in under a second. This is what the brain is doing when we’re sitting quietly not carrying out some task. If you don’t know how we measure it using functional mMRI skip to the **** and then come back. I’m not a fan of functional MRI (fMRI), the pictures it produces are beautiful and seductive, and unfortunately not terribly repeatable.

If [ Neuron vol. 82 pp. 695 – 705 ’14 ] is true than all the work on the default network should be repeated.

Why?

Because they found that less than half of 71 subjects studied were stably awake after 5 minutes in the scanner. E.g. they were actually asleep part of the time.

How can they say this?

They used Polysomnography — which simultaneously measures tons of things — eye movements, oxygen saturation, EEG, muscle tone, respiration pulse; the gold standard for sleep studies on the patients while in the MRI scanner.

You don’t have to be a neuroscientist to know that cognition is rather different in wake and sleep.

Pathetic.

****

There are now noninvasive methods to study brain activity in man. The most prominent one is called BOLD, and is based on the fact that blood flow increases way past what is needed with increased brain activity. This was actually noted by Wilder Penfield operating on the brain for epilepsy in the 30s. When the patient had a seizure on the operating table (they could keep things under control by partially paralyzing the patient with curare) the veins in the area producing the seizure turned red. Recall that oxygenated blood is red while the deoxygenated blood in veins is darker and somewhat blue. This implied that more blood was getting to the convulsing area than it could use.

BOLD depends on slight differences in the way oxygenated hemoglobin and deoxygenated hemoglobin interact with the magnetic field used in magnetic resonance imaging (MRI). The technique has had a rather checkered history, because very small differences must be measured, and there is lots of manipulation of the raw data (never seen in papers) to be done. 10 years ago functional magnetic imaging (fMRI) was called pseudocolor phrenology.

Some sort of task or sensory stimulus is given and the parts of the brain showing increased hemoglobin + oxygen are mapped out. As a neurologist, I was naturally interested in this work. Very quickly, I smelled a rat. The authors of all the papers always seemed to confirm their initial hunch about which areas of the brain were involved in whatever they were studying. Science just isn’t like that. Look at any issue of Nature or Science and see how many results were unexpected. Results were largely unreproducible. It got so bad that an article in Science 2 August ’02 p. 749 stated that neuroimaging (e.g. functional MRI) has a reputation for producing “pretty pictures” but not replicable data. It has been characterized as pseudocolor phrenology (or words to that effect).

What was going on? The data was never actually shown, just the authors’ manipulation of it. Acquiring the data is quite tricky — the slightest head movement alters the MRI pattern. Also the difference in NMR signal between hemoglobin without oxygen and hemoglobin with oxygen is small (only 1 – 2%). Since the technique involves subtracting two data sets for the same brain region, this doubles the error.

How badly are thy researchers, O default mode network

If you Google “default mode network” you get 32 million hits in under a second. This is what the brain is doing when we’re sitting quietly not carrying out some task. If you don’t know how we measure it using functional mMRI skip to the **** and then come back. I’m not a fan of functional MRI (fMRI), the pictures it produces are beautiful and seductive, and unfortunately not terribly repeatable.

If [ Neuron vol. 82 pp. 695 – 705 ’14 ] is true than all the work on the default network should be repeated.

Why?

Because they found that less than half of 71 subjects studied were stably awake after 5 minutes in the scanner. E.g. they were actually asleep part of the time.

How can they say this?

They used Polysomnography — which simultaneously measures tons of things — eye movements, oxygen saturation, EEG, muscle tone, respiration pulse; the gold standard for sleep studies on the patients while in the MRI scanner.

You don’t have to be a neuroscientist to know that cognition is rather different in wake and sleep.

Pathetic.

****

There are now noninvasive methods to study brain activity in man. The most prominent one is called BOLD, and is based on the fact that blood flow increases way past what is needed with increased brain activity. This was actually noted by Wilder Penfield operating on the brain for epilepsy in the 30s. When the patient had a seizure on the operating table (they could keep things under control by partially paralyzing the patient with curare) the veins in the area producing the seizure turned red. Recall that oxygenated blood is red while the deoxygenated blood in veins is darker and somewhat blue. This implied that more blood was getting to the convulsing area than it could use.

BOLD depends on slight differences in the way oxygenated hemoglobin and deoxygenated hemoglobin interact with the magnetic field used in magnetic resonance imaging (MRI). The technique has had a rather checkered history, because very small differences must be measured, and there is lots of manipulation of the raw data (never seen in papers) to be done. 10 years ago functional magnetic imaging (fMRI) was called pseudocolor phrenology.

Some sort of task or sensory stimulus is given and the parts of the brain showing increased hemoglobin + oxygen are mapped out. As a neurologist, I was naturally interested in this work. Very quickly, I smelled a rat. The authors of all the papers always seemed to confirm their initial hunch about which areas of the brain were involved in whatever they were studying. Science just isn’t like that. Look at any issue of Nature or Science and see how many results were unexpected. Results were largely unreproducible. It got so bad that an article in Science 2 August ’02 p. 749 stated that neuroimaging (e.g. functional MRI) has a reputation for producing “pretty pictures” but not replicable data. It has been characterized as pseudocolor phrenology (or words to that effect).

What was going on? The data was never actually shown, just the authors’ manipulation of it. Acquiring the data is quite tricky — the slightest head movement alters the MRI pattern. Also the difference in NMR signal between hemoglobin without oxygen and hemoglobin with oxygen is small (only 1 – 2%). Since the technique involves subtracting two data sets for the same brain region, this doubles the error.