Assessment of the Trajectory of Neuroimaging and Neurochemical Data over the Migraine Cycle

• Applicant: Privatdozent Enrico Schulz, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Radiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550987143

Migraine is a complex neurological disorder that affects approximately 12% of the population. Recurring headache episodes are often the most disabling symptom reported by migraineurs, however, migraine is more than "just" the headache. Typical migraine attacks last up to 48 hours and involve up to four phases: the prodromal phase, the aura phase, the headache phase, and the postdrome phase. The interictal phase between migraine attacks is defined as more than 48 hours before and after the headache phase. The distinctive feature of migraine is its cyclical nature. The clinical picture illustrates this: headache and other (sensory and vegetative) symptoms occur in recurrent episodes. In addition, patients report individual trigger factors associated with the hypothalamus, which is intensively discussed as the biological rhythm generator of migraine. The few neuroscientific studies that applied a longitudinal design also show migraine cycle-dependent changes in the brain, including an interictal sensory habituation deficit that normalizes shortly before and during the headache attack, as well as changes in hypothalamic activity and connectivity. Our project aims to assess the cyclicity of migraine in a group of 20 episodic migraine patients over a longer period (five migraine cycles) at close intervals (every 1-2 days) using the following parameters: Changes in the brain as assessed by neuroimaging. MR imaging across several migraine cycles per patient to assess perfusion (arterial spin labelling) and functional and network connectivities ("resting-state" sequences). Neurochemical indicators of migraine as assessed by calcitonin gene-related peptide (CGRP) levels in tear fluid. Repeated measures enable us to determine individually unique cortical signatures of migraine, which can help to develop neuro-modulatory interventions for episodic migraine (e.g. a tailored neurofeedback (NFB) paradigm). Migraine patients can be trained to exclusively modulate the processes that are relevant for themselves to prevent frequent migraine attacks by extending the pain-free period. The decisive neuronal processes that trigger a migraine attack occur before the headache, namely during the prodromal phase. The proposed parameters (neuronal perfusion and connectivities, CGRP levels) represent complementary aspects of migraine disease and their cyclical changes may serve as a marker for predicting an approaching attack. Moreover, these parameters may also be a target for neuro-modulatory therapies, particularly through our focus on the individual cortical signatures of migraine patients.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Katharina Kamm; Privatdozentin Dr. Ruth Ruscheweyh; Dr. Anne Stankewitz