Amygdala Connectivity May Predict CBT Efficacy for Adolescent Migraine

Frustrated female Hispanic college student has a headache while studying for an exam. She is rubbing her temples.
Connectivity between the amygdala and specific brain regions may predict headache reduction after cognitive behavioral therapy for adolescent migraine.

Greater functional connectivity between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus prior to cognitive behavioral therapy (CBT), as assessed by functional magnetic resonance imaging (MRI), may be predictive of greater headache reduction following CBT among adolescents with migraine, according to study results published in Pain.

Previous data have indicated that CBT shows potential for headache reduction in patients who suffer from migraine. There is limited data, however, on which types of patients will respond effectively to it. The goal of this study was to assess if baseline brain function and amygdalar connectivity, as determined by functional MRI, or pain modulation capacities, as determined by the conditioned pain modulation (CPM) response, can predict headache days reduction following CBT in adolescents in migraine.

The study included 20 adolescents between the ages of 10 and 17 years (mean age, 14.8±2.2 years) from the Cincinnati Children’s Headache Center who were diagnosed with migraine by a headache neurologist. All patients had 8 to 28 headache days/month with corresponding disability scores of 10 to 140, as assessed with the Pediatric Migraine Disability Assessment Scale. Prior to the start of CBT, patients completed a 28-day headache diary. They then underwent a subsequent baseline visit, which consisted of questionnaires, an MRI scan, and psychological testing.

All participants completed 8 weekly CBT sessions. A daily headache diary was completed during the 8 weeks. The study researchers allowed patients to use medications for the acute treatment of a headache attack throughout the 8 weeks of CBT sessions. At the end of this time period, patients completed a visit similar to the baseline visit. The primary outcome measure was the change in the absolute number of headache days from the baseline visit to the end of the study.

The study researchers observed a significant reduction in the frequency of headaches from before CBT to after CBT (14.6±7.4 days vs 9.9±7.2 days, respectively; P <.001). Functional connectivity of the right amygdala at baseline was associated with post-CBT reductions in headache days in specific brain regions, particularly in the frontal gyrus (P =.001), anterior cingulate cortex (P <.001), and precentral gyrus (P =.001). A greater reduction in the number of post-CBT headache days was associated with less efficient CPM response prior to CBT at the trapezius (P =.028) but not with CPM responses at the leg (P =.309).

Limitations of this study included its small sample size, the lack of a control group, and the inability of functional connectivity analysis to convey the direction of a relationship between two brain regions.

The investigators of this study suggested that the identified predictors of CBT efficacy “can lead to a personalized medicine approach in which patients with the greatest likelihood of a positive response are directed towards CBT, yielding both cost savings and greater acceptance of CBT as a treatment for migraine.”


Nahman-Averbuch H, Schneider II VJ, Chamberlin LA, et al. Identification of neural and psychophysical predictors of headache reduction following cognitive behavioral therapy in adolescents with migraine. Pain. Published online August 5, 2020. doi:10.1097/j.pain.0000000000002029