Migraines caused by different blood supply to the brain

Research shows that those who suffer from migraines may have a different way that blood is supplied to the brain.

In the UK alone, it is estimated that there are 190,000 migraine attacks per day. Migraines cause insufferable pain and can affect day-to-day living dramatically too – they can cause dramatic mood changes, and the throbbing pain can make it difficult or even impossible to sleep, work – and yet researchers have found it extremely difficult to pinpoint what causes them.

Now research published in PLOS ONE indicates that migraine sufferers have different arterial networks supplying the brain and this could help explain the cause.

Blood supply to the brain is slightly different to other parts in that it is protected by connections between the major arteries, thereby helping to ensure bloodflow at all times.

These connections are named ‘circle of Willis’ after the doctor who first pinpointed them. It’s these connections that appear to be different in people with migraine. Researchers from the Perelman School of Medicine at the University of Pennsylvania, US, looked at 170 people – one group who had no headaches, another who had migraine with aura, and one more group who had migraine without aura. Migraine with aura is defined as being typified by visual disturbances such as flashes of light, blind spots or tingling in the hands or face.

While 51% of people without headaches had an incomplete circle of Willis, the figures were significantly higher for those who did: 73% of people with migraine with aura; and 67% of those with migraine without aura.

Interestingly, when the researchers did magnetic resonance imaging to assess bloodflow they found that abnormalities in the circle of Willis were most prominent in the part of the brain that deals with vision. This, say the researchers, might explain why migraine sufferers often report seeing distortions, spots or wavy lines. The researchers are keen to point out, though, that the differences in circle of Willis between individuals is unlikely to be the only factor leading to migraine, and that other factors are almost certainly involved too. They do, however, suggest that checking the circle of Willis in patients could help pinpoint which contributory factors a patient has, thereby helping researchers move forward with testing different types of treatment.

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Variations in brain arteries may explain migraine headaches

New research shows that variations in the structure of brain arteries might explain why some people experience migraine headaches.

The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports. Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.

The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the "circle of Willis" after the English physician who first described it in the 17th century. People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.

Migraine affects an estimated 28 million Americans, causing significant disability. Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals. In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.

"People with migraine actually have differences in the structure of their blood vessels -- this is something you are born with," said the study's lead author, Brett Cucchiara, MD, Associate Professor of Neurology. "These differences seem to be associated with changes in blood flow in the brain, and it's possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."

In a study of 170 people from three groups -- a control group with no headaches, those who had migraine with aura, and those who had migraine without aura -- the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent). The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.

"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located. This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines," said the study's senior author, John Detre, MD, Professor of Neurology and Radiology.

Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual. The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient. Treatment strategies might then be personalized and tested in specific subgroups.

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Infant brain's blood flow is regulated differently than an adult brain

Researchers found the blood flow in a developing infant's brain is not the same as an adult's brain. This has many implications for treating developmental disorders.

A new study by Columbia Engineering researchers finds that the infant brain does not control its blood flow in the same way as the adult brain. The paper, which the scientists say could change the way researchers study brain development in infants and children, is published in the February 18 Early Online edition ofProceedings of the National Academy of Sciences (PNAS).

"The control of blood flow in the brain is very important" says Elizabeth Hillman, associate professor of Biomedical Engineering and of Radiology, who led the research study in her Laboratory for Functional Optical Imaging at Columbia. "Not only are regionally specific increases in blood flow necessary for normal brain function, but these blood-flow increases form the basis of signals measured in fMRI, a critical imaging tool used widely in adults and children to assess brain function. Many prior fMRI studies have overlooked the possibility that the infant brain controls blood flow differently."

"Our results are fascinating" says Mariel Kozberg, a neurobiology MD-PhD candidate who works under Hillman and is the lead author of the PNAS paper. "We found that the immature brain does not generate localized blood-flow increases in response to stimuli. By tracking changes in blood-flow control with increasing age, we observed the brain gradually developing its ability to increase local blood flow and, by adulthood, generate a large blood-flow response."

The study results suggest that fMRI experiments in infants and children should be carefully designed to ensure that maturation of blood-flow control can be delineated from changes in neuronal development. "On the other hand," says Hillman, "our findings also suggest that vascular development may be an important new factor to consider in normal and abnormal brain development, so our findings could represent new markers of normal and abnormal brain development that could potentially be related to a range of neurological or even psychological conditions."

Functional magnetic resonance imaging, or fMRI, is one of several brain-imaging methods that measure changes in blood flow to detect the presence and location of neuronal activity. In adults, blood-flow increases occur in specific regions of the brain during a particular task like moving your hand or reacting to a stimulus. FMRI relies upon measuring decreases in deoxygenated hemoglobin resulting from this blood-flow increase to understand which parts of the brain are responsible for different actions and emotions. FMRI and other brain-imaging methods are currently being widely used to explore brain development, and to understand disorders in infants and children including autism and ADHD.

"Until now, we had been studying blood flow in the adult brain," Hillman notes, "but we became interested in several studies that reported odd, sometimes negative, blood-flow responses in newborn and premature infants and decided to carefully explore what was different about the immature brain compared to the adult. Initially, I saw these studies as a way to watch how the adult system assembled itself during development. Then we realized how important our findings were to those using brain imaging to study child development and developmental disorders."

The team used a unique multispectral optical intrinsic signal imaging system (MS-OISI) built in Hillman's lab to perform the research. MS-OISI is a high-speed, high-resolution imaging approach that takes advantage of the different absorption spectra of deoxygenated and oxygenated hemoglobin in order to determine changes in the concentrations of each. The researchers found that, with increasing age, there was a gradual development of a localized increase in blood flow, while a strong, delayed decrease in flow was consistently present. Only by adulthood was the positive increase able to balance the decrease in flow.

"Our results suggest that the infant brain might not be able to generate localized blood- flow increases, even if there is neuronal activity occurring, and that the development of blood- flow control occurs in parallel with early neuronal development," says Kozberg. "This could suggest that fMRI studies of infants and children may be detecting changes in both vascular and neuronal development -- in fact, vascular development may be an important new factor to consider in normal and abnormal brain development."

The team also found that the younger age groups were highly sensitive to blood pressure increases in response to stimulation and that these increases can cause large increases in blood flow across the brain. "This finding indicates that the newborn brain is also unable to regulate its overall blood-flow levels," Kozberg explains. "This could explain earlier fMRI results in infants and children that were sometimes positive and sometimes negative, because it is difficult to tell whether blood pressure increases are occurring in infants and children. This result suggests that great care should be taken in setting stimulus thresholds in young subjects."

The researchers add that, since the newborn brain appears to be able to sustain itself without tightly controlled blood flow, their findings suggest that the infant brain may be intrinsically more resistant to damage due to a lack of oxygen than the adult brain. "This could be an important property to understand, both in terms of understanding how best to treat blood-flow problems in the newborn infant brain, which can cause lifelong problems such as cerebral palsy, and to potentially better understand how to treat the adult brain in conditions such as stroke," Hillman observes.

"Our lab operates at the intersection of neuroscience and engineering," continues Hillman." Not only do we develop the imaging systems that let us investigate the living brain in new ways, but like all engineers, we're fascinated with figuring out 'how things work,' and the brain is no exception."

Next steps for Hillman and her team include further defining the cellular mechanisms underlying the developing hemodynamic response at a cellular and microvascular level, using methods such as high-speed and multi-plane in-vivo two-photon microscopy, another technique developed in the lab. They're particularly interested in tracking changes in neuronal activity, microvascular architecture and connectivity, and the distribution and activity of other cellular populations thought to be associated with neurovascular coupling as a function of development.

"This will help us understand how the neonatal brain is different, and better understand how mature blood-flow control mechanisms in the adult brain work," says Kozberg. Adds Hillman, "We are also keen to take this research into the clinic and explore whether our findings could improve diagnosis and monitoring of newborn infants. Our findings so far feel like just the tip of the iceberg. There is so much more for us to do now to understand why the infant brain is so different, and how we can use our findings to improve understanding of a wealth of devastating childhood and developmental conditions."

This research was supported by grants and student fellowships from the National Institute of Neurological Disorders and Stroke, the National Eye Institute, the National Science Foundation, the National Defense Science and Engineering Graduate Fellowship, the Medical Scientist Training Program, and the Human Frontier Science Program. Hillman is also a member of the Columbia University graduate program in Neurobiology and Behavior and the Kavli Institute for Brain Sciences.

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