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Conection Between Migraines and Cognition

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The way the brain adapts to pain is something that has been long discussed in the field of cognitive neuroscience. Although there have been some dissenting views on how migraine pain specifically impacts the ability to complete cognitive tasks while experiencing pain, this paper will discuss one of those such experiments and some potential continuations that could be taken in the future to further this field. Using the research of Mathur et al., 2015, we can begin to look at how different areas of the brain are affected by migraine pain. Although this specific study has a relatively small sample size and only includes women, it is still a very good starting place for this field of research and gives a launch point from which continued research can continue. Although the implications for this research don’t have extremely wide-reaching branches, there is still merit to learning the ways in which our brains and bodies adapt to pain over time and how that might affect us in ways that we were previously unaware of.

In the original paper migraines and brain activity with pain were investigated. (Mathur et al., 2015). Using a varied set of task difficulty and heat/pain and fMRI to look at what areas of the brain were being recruited the most or being suppressed, the researchers were interested in looking at the way migraines affect the long-term physiology of the brain. They used a matched design and had fourteen healthy patients as well as fourteen patients that were plagued with migraines. Ten of the fourteen migraine patients were described as chronic migraine patients (14-28 migraines per 28 days), while the other four migraine patients were described as episodic migraine patients (7.8-13.7 migraines per 28 days). The healthy participants were matched to the migraine patients based on education as well as what hand they would use to press the button that was used in the cognitive task.

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Although there have been some studies on migraines and cognition in the past, they have come up with some mixed results. According to de Arujo et al., 2012, the results of the study depends on where the migraine patients are recruited from. Migraine patients that were recruited from the streets tended to have less cognitive impact from their migraines than patients that were taken from neurological clinics. In this study the migraine patients were taken from Johns Hopkins University campuses, local headache clinics as well as advertisements around the community. This could lead to potentially skewed results based on the review that de Arujo et al., had conducted, but this study does not take that into account. The main focus of this study was to determine how migraines affect cognition in long term sufferers, and they hypothesized that the migraine patients will show different areas of brain activity during the moderate pain level task due to functional restructuring of the brain in order to function more regularly during high pain periods of their frequent migraines.

Like stated in the above paragraph, the methods of this study involved a matched design of 14 chronic migraine patients to 14 regular people. They were matched based on their education level as well as dominant hand. This study involved three levels of pain induced by a heat stimulus and two different difficulties of cognitive games. The three pain stimuluses were listed as: no pain (37 degrees Celsius), mild pain (one degree Celsius less than the moderate pain stimulus), and moderate pain. The moderate pain stimuli were determined before the actual study took place and was the point where the patients indicated a pain level of 5-6 on a 0-10 pain scale. The other part of this experiment involved the use of a clicker and a computer screen. The goal of the cognitive task is to determine what direction a center arrow is facing while ignoring the arrows on the outside. There were two difficulties, the first involving flanking arrows that were in alignment and the second involved arrows that were incongruous and, “distracting”. Distracting is a very subjective term and the exact meaning of it isn’t listed but is simply described as being more difficult and more distracting than the first test.

There was a total of six possible testing situations, no pain and easy task, no pain and difficult task, mild pain and east task, mild pain and difficult task, moderate pain and easy task, moderate pain and difficult task. This gave the researchers a large sample of data to work with while keeping the range of data the received relatively small. Before getting strapped up to the fMRI, all the patients went through a training session where they practiced the cognitive task until they got an accuracy of 90% or higher (which difficulty this was done at is not stated).

Once the patients got used to the cognitive task, they went through a trial run of the actual experiment where all 6 test modules were used in the same style they would go through during the actual experiment taking note of reaction time and recording pain levels. They wanted to get the initial pain levels because there have been studies that show migraine patients tend to catastrophize pain more than healthy individuals and therefor may focus more on the pain and less on the cognitive task even if the levels of pain are consistent between the non-migraine and migraine subjects. Once the subjects had completed the dry run, they went through the MRI sessions. Each subject went through two runs with fMRI attached. Each run contained 27 trials but only having 6 trial types means that some of the trials were preferred over others and it is not listed what trials were preferred or if the trials were random.

Using Matlab and SPM8 software the researchers time corrected and motion corrected the images. Once corrected the researchers took the images and placed them over the mean functional image and segmented the parts into CSF, white matter and gray matter. The volumes were then normalized using a Gaussian kernel which creates a bell curve of data. After all the preprocessing had taken place the researchers analyzed all the data by participant. The models they created including six areas of interest all related to the six different structures of the test. In order to model only periods of interest the researchers shaved off small portions of each test at the beginning and end in order to focus the information they were receiving. This was constant for the cognitive information at 1.4 seconds of both ends of the cognitive trial but included more variation in the thermal trials. To evaluate the differences based on task for each participant they took the no pain tests for both the easy and difficult cognitive task for all participants and compared them using independent sample t-tests. The researchers also compared the remaining two tests, and using the same methods compared the mild and moderate pain tests. Further testing involved looking at different activation levels and subtracting them to get activations as well as deactivations. This included all tests and groups. Finally, they looked at the specific effects that the difficult task had in order to see the way cognitive load was handled by the test groups.

Looking at all of the data they gathered is a daunting task considering how many different variables there are to control, but the easiest points to make right off the bat are the ways that difficulty affects reaction time as well as how pain marginally affected the speed of reaction. Also, the difficulty of the task affected the accuracy of the tests but surprisingly the pain levels did not have any affect on the accuracy of the subjects. Like discussed earlier, the migraine patients had significantly higher pain catastrophizing scores compared to the control, a mean of 17.7 vs a mean of 6.9 for the groups. Looking at the fMRI results across pain conditions the control group displayed higher activation of the left ventral region of the primary motor cortex compared to the migraine patients. Although this difference is visible, using cluster-level correction the difference becomes insignificant. Without including pain as a stimulus, migraine patients showed less deactivation of the lateral dorsolateral prefrontal cortex as well as regions in the dorsal anterior cingulate cortex and cerebellum during the more difficult cognitive tasks compared to the easier task. The four patients that were described as episodic migraine sufferers were not outliers in these results. The control patients however showed greater activation of the dorsal superior frontal gyrus compared to the migraine patients when compared on the full task including pain interactions. Among the control group, activation within a precuneus cluster reflects the interaction the best which may suggest a different pattern of activity within the two groups. Overall, more widespread deactivations were observed among the migraine group relative to the control patients.

Taking all of this information, the researchers concluded that migraine patients have reduced cognitive related neuronal activity in brain regions associated with cognitive processing and had altered patterns of activity when looking at the pain cognition interactions when compared to the healthy/control group. Although most of the prior studies had results that could never quite agree, this study shows that there is some long-term restructuring that occurs in patients with long term migraine conditions. This is concurrent with the study by Baliki et al., 2008, so it hasn’t really changed the way that this information has been perceived by the scientific community. This study was generally conducted well, but there was some information that was lost that couldn’t be used for the results, and there was a relatively small study group that did not have wide reaches on who it could relate to. Only using females is a big limiter to how much the results of this study can extend to the field of cognitive science, but there was a good control group assigned, and they had a myriad of experimental setups that allowed for a large comparison of results between subjects and between differing variables.

If I were to add a study onto this on in order to further this research I would absolutely start by increasing sample size and broadening the scope of the study so that the results can be used by a wider field and it is not limited to one gender and age group. Unfortunately in order to get any sort of experiment funded and passed by the FDA or whatever other group you may need, you have to limit the amount of pain that the participants receive, but increasing the pain may yield interesting results as the stress begins to reach higher levels and different areas of the brain are recruited. Although I think the cognitive task, they used was a good one, I think altering the task to be an auditory task instead of a visual task might reveal a bias for the migraine patients, especially if they have auditory pain and sensitivity when they have migraines. So, getting a much larger sample size of mixed genders and preferably younger individuals would be the start. Preferably somewhere in the 20’s age wise as an average and then maybe test again with individuals who are a little bit older like in their 40’s to see how the longer the migraines continue the more it begins to impact the structure and function of the brain.

It would be hard to come up with an auditory task that doesn’t involve reflexes because that is a potential area of bias that is not accounted for nor can be accounted for. This study did show that reflex times are something that can have most of their variability removed by using multiple levels of tests and placing your patients against each other for those types of tests. The auditory test that could be used may involve distinguishing which side a certain sound came from, but its hard to create different levels of difficulty with audition. It may be easier and more feasible to continue with the visual cognitive tasks. The arrow test was a good that excludes a lot of potential issues that other types of visual tests may include. A test with colors is probably not a good design, nor is a test that involves any sorts of letters or words. Pattern recognition tests might be another style of testing that shows good results and wouldn’t be very challenging to set up. With pattern recognition there has already been so much research done for the purpose of IQ testing so it would not be hard to categorize the tests into even more difficulties and see how potentially even harder tests are handled by the brain. It may be interesting to try different pain applications like a prick, or electric shock in order to see how all forms of pain are interpreted.

Although there are a lot of different ways that this test can be modified, I don’t see much benefit of modifying it in that many ways. The basis of the research is here, and the most important thing in finding the validity of theses tests in to broaden the field of applicability and widening the test pool.

One thing that would add significant information to this field of study is to study other long-term mental pain diseases such as fibromyalgia and lupus for example. Those are also diseases that include large amounts of constant pain, so looking at the way those compare in terms of long-term physiological changes to the brain. That would give a much broader look at how pain impacts the brain and the way it evolves to cope with pain over time. The applications of this study outside of its immediate field seem quite small. It doesn’t seem there is very much carryover in terms of what these studies can be applied to besides better understanding how the brain adapts to pain and what changes that can have on a person throughout their lives. 

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