1. Kevin Bach Caterina Mainero, Jasmine Boshyan, and Nouchine Hadjikhani

2. Overview  Introduction  Hypothesis  Methods  Results  Discussion  Strengths & Limitations  Personal Opinion

3. What is a migraine?  A common type of headache  Additional symptoms: Nausea Vomiting Sensitivity to light Sensitivity to sound  Pain is usually felt only on one side of the head

4. Introduction  Current concepts of migraine: neurological disorder Broad sensory processing dysfunction  Periaqueductal Gray Matter (PAG) Key area for migraine Known modulator of somatic pain Subjects without headaches developed migraine-like episodes after electrode placement in PAG Abnormalities in the PAG of migraineurs often paralleled by structural changes in connected brain regions involved in pain processing and modulation

5. Introduction  Prevailing theory in the cause of the migraine attack: Hyperexciatability along neurons in the trigeminal nerve that innervate cerebral blood vessels ○ Facilitated by dysfunction of the pain modulatory circuits  Previous studies show hypofunction of pain modulatory circuits during the interictal phase of migraine Might contribute to the development of the migraine attack

6. Hypothesis 1) Intrinsic connectivity within the PAG and somatosensory/pain processing and modulatory pathways would be dysfunctional in migraineurs relative to age-matched healthy subjects 2) These alterations would be associated with disease severity as measured by the frequency of migraine attacks per month

7. Methods  Resting-state fMRI  17 patients with episodic migraine 15 females 2 males 32.4 ± 8.2 years old All patients migraine free for at least 72 hours Migraines per Month  17 gender- and age-matched healthy subjects No history of migraine or other headache types

8. Results  Both groups showed predominantly positive correlations between PAG and cortical regions involved in pain and somatosensory processing  Correlations more prevalent in migraineurs  Higher the migraine frequency Greater connectivity between the PAG and the hypothalamus, anterior insula, brainstem Lower connectivity between the PAG and the prefrontal cortex, anterior cingulate, amygdala

9. Discussion  Interictal increase in resting-state connectivity between the PAG and both nociceptive and sensory processing pathways in migraineurs compared to controls Could reflect a hyperexcitability of pain pathways  The greater the number of migraine attacks per month: Stronger connectivity between the PAG and both nociceptive and sensory processing pathways Weaker connection between the PAG and brain regions with a role in pain modulation

10. Discussion  PAG is known to regulate the brainstem pain-inhibiting circuitry  Prefrontal cortex controls functional interactions among nociceptive brain regions to modify perceptual correlates of pain through pain-inhibitory mechanisms Reduced connectivity between PAG and prefrontal cortex correlated with the increase in migraine attack frequency  Development of migraines may be a result of an interictal dysfunction of the inhibitory system

11. Strengths, Limitations & Future Studies  Looked at the relation between migraine severity and the degree of dysfunction within PAG networks  Resting brain activity is either increased or decreased in other chronic pain conditions Future studies may clarify whether observed changes are a signature of migraines or are shared by other chronic pain conditions

12. My opinion  Slightly difficult to understand Many brain areas involved Not much known about migraines & pain pathways  Pleased to see progress in the understanding of migraines

13. Thank you