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Showing posts with label Migraine. Show all posts
Showing posts with label Migraine. Show all posts
October 7, 2009
September 28, 2009
Migraine aura simulation
As an update to the blog post Seeing zigzags, I created a movie based on the neural network simulation described there.
By the way, my new brain arrived. No, the old one did not hurt too much, in fact, you may want to read how actually the migraine pain is generated.
By the way, my new brain arrived. No, the old one did not hurt too much, in fact, you may want to read how actually the migraine pain is generated.
September 23, 2009
The migraine headache
Our recent understanding of the anatomy of headaches could lead to new treatments. One debated scenario is that a spreading depression wave causes the pain by releasing substances that activate pain-sensitive nerve fibers
Today, I ordered a human brain anatomy model. I had to choose from over two dozen models. The simplest version would have sufficed to demonstrate the migraine wave patterns propagating on the surface of the brain. I decided to go for the deluxe brain. Who wouldn't?
While waiting for my new deluxe brain, I thought it is a nice idea to kill time and explain where according to current hypotheses the roots of migraine headaches are. In fact, I really chose the deluxe version, because I need the add-on stuff like the arteries and the opened head base to explain to my physics students the pathway and anatomy of migraine headaches.
Usually, I do not talk about headache although I work in migraine research now for almost 18 years. No wonder, a safe bet is that I will be asked after a conference talk: What about the headache?
Well, I'm interested in pattern formation in brain tissue related to migraine. Neither gray nor white matter can hurt, simply because brain tissue lacks pain-sensitive nerve fibers. So I may open my talk mentioning that headache is a symptom while migraine is a disease and therefore one should not say migraine is a headache, but that is all. Unless being asked explicitly.
But our recent understanding of the anatomy of headaches suggests that these pattern formation processes that I study, that is, a reaction-diffusion wave called spreading depression causes the pain by releasing substances that then activate pain-sensitive nerve fibers in the brainstem. So finally I got interested.
Lithograph plate of the trigeminal nerve. This nerve is sends sensory information from the face to the brainstem. From Henry Gray's Anatomy of the Human Body
All sensory information from the face, that is, also pain, is sent to a sort of relay station, the trigeminal nucleus. It extends throughout the entire brainstem. During a migraine, this nucleus gets abnormally activated, which eventually causes the pain. Firstly, neurotransmitters are released from the spreading depression wave in the cortex. This in turn will activate the trigenimal network. Signals from the trigenimal nucleus will then be send upwards along the remaining pain pathway. They pass through another relay station, the thalamus before they finally reach their destination, the sensory cortex. There, the sensation of pain is created. As a consequence, if we could stop the wave process, which is believed to be at the start of this cascade, we also stop the headache.
A second scenario says that actually the brainstem causes both, the spreading depression wave and the pain. The pain is either activated by the induced spreading depression wave, as described above, or the brainstem could independently trigger the pathway to the sensory cortex.
It remains to be seen in which direction this debate is going. It will probably not be quickly decided. So my physics students have some time to learn anatomy, once my deluxe brain arrived.
Today, I ordered a human brain anatomy model. I had to choose from over two dozen models. The simplest version would have sufficed to demonstrate the migraine wave patterns propagating on the surface of the brain. I decided to go for the deluxe brain. Who wouldn't?
While waiting for my new deluxe brain, I thought it is a nice idea to kill time and explain where according to current hypotheses the roots of migraine headaches are. In fact, I really chose the deluxe version, because I need the add-on stuff like the arteries and the opened head base to explain to my physics students the pathway and anatomy of migraine headaches.
Usually, I do not talk about headache although I work in migraine research now for almost 18 years. No wonder, a safe bet is that I will be asked after a conference talk: What about the headache?
Well, I'm interested in pattern formation in brain tissue related to migraine. Neither gray nor white matter can hurt, simply because brain tissue lacks pain-sensitive nerve fibers. So I may open my talk mentioning that headache is a symptom while migraine is a disease and therefore one should not say migraine is a headache, but that is all. Unless being asked explicitly.
But our recent understanding of the anatomy of headaches suggests that these pattern formation processes that I study, that is, a reaction-diffusion wave called spreading depression causes the pain by releasing substances that then activate pain-sensitive nerve fibers in the brainstem. So finally I got interested.
Lithograph plate of the trigeminal nerve. This nerve is sends sensory information from the face to the brainstem. From Henry Gray's Anatomy of the Human Body
All sensory information from the face, that is, also pain, is sent to a sort of relay station, the trigeminal nucleus. It extends throughout the entire brainstem. During a migraine, this nucleus gets abnormally activated, which eventually causes the pain. Firstly, neurotransmitters are released from the spreading depression wave in the cortex. This in turn will activate the trigenimal network. Signals from the trigenimal nucleus will then be send upwards along the remaining pain pathway. They pass through another relay station, the thalamus before they finally reach their destination, the sensory cortex. There, the sensation of pain is created. As a consequence, if we could stop the wave process, which is believed to be at the start of this cascade, we also stop the headache.
A second scenario says that actually the brainstem causes both, the spreading depression wave and the pain. The pain is either activated by the induced spreading depression wave, as described above, or the brainstem could independently trigger the pathway to the sensory cortex.
It remains to be seen in which direction this debate is going. It will probably not be quickly decided. So my physics students have some time to learn anatomy, once my deluxe brain arrived.
August 11, 2009
Hassenstein's vision for migraine relief
In 1979, Bernhard Hassentstein came to the truly remarkable conclusion that an avenue for migraine relief, cure or prevention may open up by investigating visual disturbances—30 years later, we stay at the beginning of this avenue
Bernhard Hassenstein, born in 1922, is a German behavioral biologist and one of the early founders of biological cybernetics. In 1981, he was asked to contribute a chapter to a book celebrating the 70th birthday of Klaus Piper, owner of the Munich-based publisher Piper Verlag. He thought about a topic that could be both enjoyable and academic. He came up with "Five variations about my migraine".
In his last, the fifth episode from 1979, Hassenstein describes very precise measurements of the position of his migraine aura within the visual field. He estimates that the disturbance, which causes his visual migraine symptoms, propagates in the gray matter surface of the brain, that is, the cortex, with a constant velocity. For this he assumed that the inverse cortical magnification factor increases linearly with eccentricity. Simply speaking, there is a rather simple scaling law how visual input from the eye is magnified in our brain so that acuity is largest in the center of gaze. Similar data were published, for example, later by Otto-Joachim Grüsser.
Hassenstein concluded (in his own words):
"private Migräne könnte dereinst zur besseren Aufklärung [...] beitragen und darauf folgend vielleicht sogar zur Linderung, Heilung oder Vorbeugung. Denn die Meßkurven beweisen, daß die Störung ... im Gehirn abläuft."
"... my private migraines could some day contribute to explain migraine and even to its relief, cure or prevention. For the measurements are evidence of a disturbance in the brain."
[my translation]
Full essay is only available in German:
I learned about this from Bernhard Hassenstein in the mid 1990ies during Manfred Eigen's famous Winterseminars "Biophysical Chemistry, Molecular Biology and Cybernetics of Cell Functions" in Klosters (Swiss). It inspired me to take a closer look at the spatio-temporal development of migraine aura symptoms, which—exactly 30 years after Hassenstein's first visionary self oberservations—led to the recent migraine fMRI study in PLoS ONE. This article is also described for a wider public in a separate blog post.
At the internationally renowned Technische Universität Berlin, we study in newly funded projects within the next years the unique set of data, which I collected over the last 15 years, linking physiological and mathematical pictures of migraine to further explore Hassenstein's vision.
Reference:
Pflieger M, Piper, ER (Eds). Für Klaus Piper zum 7O. Geburtstag 27. März 1981. ' Piper-Verlag, München 1981
Bernhard Hassenstein, born in 1922, is a German behavioral biologist and one of the early founders of biological cybernetics. In 1981, he was asked to contribute a chapter to a book celebrating the 70th birthday of Klaus Piper, owner of the Munich-based publisher Piper Verlag. He thought about a topic that could be both enjoyable and academic. He came up with "Five variations about my migraine".
In his last, the fifth episode from 1979, Hassenstein describes very precise measurements of the position of his migraine aura within the visual field. He estimates that the disturbance, which causes his visual migraine symptoms, propagates in the gray matter surface of the brain, that is, the cortex, with a constant velocity. For this he assumed that the inverse cortical magnification factor increases linearly with eccentricity. Simply speaking, there is a rather simple scaling law how visual input from the eye is magnified in our brain so that acuity is largest in the center of gaze. Similar data were published, for example, later by Otto-Joachim Grüsser.
Hassenstein concluded (in his own words):
"private Migräne könnte dereinst zur besseren Aufklärung [...] beitragen und darauf folgend vielleicht sogar zur Linderung, Heilung oder Vorbeugung. Denn die Meßkurven beweisen, daß die Störung ... im Gehirn abläuft."
"... my private migraines could some day contribute to explain migraine and even to its relief, cure or prevention. For the measurements are evidence of a disturbance in the brain."
[my translation]
Full essay is only available in German:
I learned about this from Bernhard Hassenstein in the mid 1990ies during Manfred Eigen's famous Winterseminars "Biophysical Chemistry, Molecular Biology and Cybernetics of Cell Functions" in Klosters (Swiss). It inspired me to take a closer look at the spatio-temporal development of migraine aura symptoms, which—exactly 30 years after Hassenstein's first visionary self oberservations—led to the recent migraine fMRI study in PLoS ONE. This article is also described for a wider public in a separate blog post.
At the internationally renowned Technische Universität Berlin, we study in newly funded projects within the next years the unique set of data, which I collected over the last 15 years, linking physiological and mathematical pictures of migraine to further explore Hassenstein's vision.
Reference:
Pflieger M, Piper, ER (Eds). Für Klaus Piper zum 7O. Geburtstag 27. März 1981. ' Piper-Verlag, München 1981
July 11, 2009
July 2, 2009
June 12, 2009
Seeing zigzags
You can literally see how your brain works during a migraine with aura and learn first hand about cortical organization
In the article that starts with the question "Does the migraine aura reflect cortical organization?", published in the European Journal of Neuroscience, I considered the old idea that flickering zigzag patterns seen during migraine with aura reflect properties of our neurons. Let me explain this briefly.
It is well known that neurons fire much more frequently if the condition they are tuned for is met. For example, one of your neurons may only fire if you see a vertical line at a specific location in your visual field. We know very well how such neurons are organized on the surface of your brain. This is called cortical organization. In general, this concept denotes how sensory conditions that must be met for neurons to fire—such as edge orientation, but also color or any other feature of the outside world—are spatially organized on the surface of your brain. Sometimes, this is also called a cortical feature map.
It seems natural to suggest that hallucinatory zigzag patterns seen during migraine with visual aura reflect the organization in the visual cortex representing the feature edge orientation. What other than a pattern of edges is a zigzag? That migraine aura reflects cortical organization was proposed by many scientists, but how to prove or at least support this hypothesis?
My idea was to translate our current knowledge of both
cortical organization and migraine pathophysiology into a neural network model. I should then be able to reconstruct the flickering zigzag patterns seen during migraine in a computer simulation. The result is displayed on the right. In fact, the actual computer simulation is animated, but I chose a still image. Otherwise this blog would become unreadable for those who suffer from migraine. Flickering patterns can trigger migraine. For an animated version, please see my scholarpedia article Models of cortical spreading depression. We now have sample movies that can be compared with the zigzags seen during migraine, like we measure tinnitus by sample noise.
In the article that starts with the question "Does the migraine aura reflect cortical organization?", published in the European Journal of Neuroscience, I considered the old idea that flickering zigzag patterns seen during migraine with aura reflect properties of our neurons. Let me explain this briefly.
It is well known that neurons fire much more frequently if the condition they are tuned for is met. For example, one of your neurons may only fire if you see a vertical line at a specific location in your visual field. We know very well how such neurons are organized on the surface of your brain. This is called cortical organization. In general, this concept denotes how sensory conditions that must be met for neurons to fire—such as edge orientation, but also color or any other feature of the outside world—are spatially organized on the surface of your brain. Sometimes, this is also called a cortical feature map.
It seems natural to suggest that hallucinatory zigzag patterns seen during migraine with visual aura reflect the organization in the visual cortex representing the feature edge orientation. What other than a pattern of edges is a zigzag? That migraine aura reflects cortical organization was proposed by many scientists, but how to prove or at least support this hypothesis?
My idea was to translate our current knowledge of both
cortical organization and migraine pathophysiology into a neural network model. I should then be able to reconstruct the flickering zigzag patterns seen during migraine in a computer simulation. The result is displayed on the right. In fact, the actual computer simulation is animated, but I chose a still image. Otherwise this blog would become unreadable for those who suffer from migraine. Flickering patterns can trigger migraine. For an animated version, please see my scholarpedia article Models of cortical spreading depression. We now have sample movies that can be compared with the zigzags seen during migraine, like we measure tinnitus by sample noise.June 5, 2009
Seeing your brain anatomy without fMRI scan
Migraine sufferer literally sees his brain surface being curved
In the article entitled "Migraine Aura: Retracting Particle-Like Waves in Weakly Susceptible Cortex", published in the open-access journal PLoS ONE, my colleague, Nouchine Hadjikhani, and I uncovered in a rather unconventional manner the spatial form and temporal evolution of pathological activity patterns in human cortex during migraine with aura. We compared symptom reports of visual field defects with the topographic representation of these symptoms on the cortical surface obtained by non-invasive functional magnetic resonance imaging (fMRI).
Migraine maps and other maps
A keen engineer provided us with fascinating data. He marked the progression of his visual disturbances with a pencil on a sheet of paper. For about half an hour, every minute he newly outlined the location of his visual field disturbance while keeping his gaze fixed on a cross that he had drawn on the paper when the attack started. So we got many drawings, he called them migraine aura maps, each with about thirty lines.
Nouchine recorded then another map from his cortical surface—called retinotopy—using fMRI. In this map, positions in visual field are marked on the cortical surface, for example with a color code ranging from cyan (lower hemimeridian, 6 o'clock position) via blue (horizontal hemimeridian, that would be 3 o'clock) to red (upper hemimeridian, you got it). Let us first use this color code in the picture above, voilà.
What you see below is a 3D picture of the primary visual cortex with the same color code as used for azimuthal positions in the visual field.
The primary visual cortex is a credit card-size large area in the brain receiving visual information from the eyes. The cross with the 4 letters c,r,d,v mark anatomical directions and cuneus, lingual gyrus, CS, and occitipal pole are just names for anatomical landmarks known to the specialist. Important is that the primary visual cortex is organized retinotopic, that is, neighboring points in the cortex process information from neighboring points in the visual field. Without retinotopic organization, the picture would be not smoothly colored but randomly.
This retinotopic mapping allowed me to reconstruct the spatial patterns that correspond on the cortical surface to the engineer's lines in the aura map. I compared the aura map with his typical anatomical landmarks and we uncovered that the engineer actually saw his curved brain from within because there where remarkable correlations between his aura map drawing and the curved shape of his primary visual cortex.
Towards novel therapeutic methods using chaos control
These patterns revealed valuable information about the self-organization principles behind migraine pathophysiology. The gained knowledge, namely the confined location of the activity, opens up entirely new therapeutic methods based on chaos control. I work currently on intelligent neuronavigated transcraniel stimulation techniques that can be used in combination with biofeedback training via a brain-computer interface to persistently decrease susceptibility to this pathological activity in exactly the right location. My hope is that location is the key to non-pharmaceutical medical therapies using biomedically engineered approaches.
Suggested further reading:
Chaos and Migraine.
In the article entitled "Migraine Aura: Retracting Particle-Like Waves in Weakly Susceptible Cortex", published in the open-access journal PLoS ONE, my colleague, Nouchine Hadjikhani, and I uncovered in a rather unconventional manner the spatial form and temporal evolution of pathological activity patterns in human cortex during migraine with aura. We compared symptom reports of visual field defects with the topographic representation of these symptoms on the cortical surface obtained by non-invasive functional magnetic resonance imaging (fMRI).
Migraine maps and other maps
A keen engineer provided us with fascinating data. He marked the progression of his visual disturbances with a pencil on a sheet of paper. For about half an hour, every minute he newly outlined the location of his visual field disturbance while keeping his gaze fixed on a cross that he had drawn on the paper when the attack started. So we got many drawings, he called them migraine aura maps, each with about thirty lines.
Nouchine recorded then another map from his cortical surface—called retinotopy—using fMRI. In this map, positions in visual field are marked on the cortical surface, for example with a color code ranging from cyan (lower hemimeridian, 6 o'clock position) via blue (horizontal hemimeridian, that would be 3 o'clock) to red (upper hemimeridian, you got it). Let us first use this color code in the picture above, voilà.
What you see below is a 3D picture of the primary visual cortex with the same color code as used for azimuthal positions in the visual field.
The primary visual cortex is a credit card-size large area in the brain receiving visual information from the eyes. The cross with the 4 letters c,r,d,v mark anatomical directions and cuneus, lingual gyrus, CS, and occitipal pole are just names for anatomical landmarks known to the specialist. Important is that the primary visual cortex is organized retinotopic, that is, neighboring points in the cortex process information from neighboring points in the visual field. Without retinotopic organization, the picture would be not smoothly colored but randomly.
This retinotopic mapping allowed me to reconstruct the spatial patterns that correspond on the cortical surface to the engineer's lines in the aura map. I compared the aura map with his typical anatomical landmarks and we uncovered that the engineer actually saw his curved brain from within because there where remarkable correlations between his aura map drawing and the curved shape of his primary visual cortex.
Towards novel therapeutic methods using chaos control
These patterns revealed valuable information about the self-organization principles behind migraine pathophysiology. The gained knowledge, namely the confined location of the activity, opens up entirely new therapeutic methods based on chaos control. I work currently on intelligent neuronavigated transcraniel stimulation techniques that can be used in combination with biofeedback training via a brain-computer interface to persistently decrease susceptibility to this pathological activity in exactly the right location. My hope is that location is the key to non-pharmaceutical medical therapies using biomedically engineered approaches.
Suggested further reading:
Chaos and Migraine.
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