Dr. Schwedt and colleagues enrolled 120 subjects into their study—66 migraineurs and 54 healthy controls. Subjects and controls were well matched for age and sex. There were statistical differences in Beck Depression Inventory scores, although the average score of 4.1 among migraineurs was still within normal limits. The migraineurs averaged nine headache days per month, had had 16 years of migraine, and had significant disability from migraine, with an average MIDAS score of 20.5.
Testing the Models
The first classifier that was built was intended to differentiate migraineurs from healthy controls. “What we found was that overall, the average accuracy of the classifier was 68%. If we looked at an individual brain MRI, based on the structural measures, we could tell with 68% accuracy whether or not that MRI belonged to somebody who had migraine versus someone who was a healthy control,” reported Dr. Schwedt. But 68% accuracy was a little disappointing. The researchers theorized that heterogeneity within the migraine group might explain their results. So they separated out episodic and chronic migraine.
The next classifiers were an attempt to differentiate episodic migraine from healthy controls. “Unfortunately, our accuracy did not improve. It was 67%.”
But when they looked at chronic migraine, the accuracy shot up. With this classifier, the researchers could look at an individual brain MRI and tell whether it belonged to someone with chronic migraine versus a healthy control with 86% accuracy.
Next, the researchers built classifiers to differentiate chronic migraineurs from episodic migraineurs. “Again, we had pretty high accuracy—84%.”
Then the researchers probed the headache frequency threshold. They used different numbers of headache frequency to divide the migraineurs into two subsets, high frequency and low frequency. The thresholds ranged from five headache days per month to 15 headache days per month. For each of those thresholds, the researchers built classifiers based upon brain structure to see which cut-point yielded the most accurate classification, based upon brain structure. “And what we found was that, in fact, 15 headache days per month was the best headache frequency threshold for differentiating the migraineurs into two subgroups. And that’s consistent with our current use of 15 headache days per month to divide migraineurs into episodic versus chronic migraine,” Dr. Schwedt said. “We now have some objective data based upon brain structure that actually supports the use of the 15 headache days per month cut-point.”
Brain Regions Involved
The brain regions that most frequently contributed to the classifiers include the temporal pole, superior temporal lobe, anterior cingulate cortex, entorhinal cortex, medial orbital frontal gyrus, and the pars triangularis. “Each of these regions participates in pain processing, but they participate in different ways,” Dr. Schwedt noted. Some are more important for emotional response to pain, some play a more cognitive role in pain processing, and others are more important for multisensory integration. “So it is kind of a complex picture,” he said. “And this is really what we should expect.”
—Glenn S. Williams