Neurophysiology of altered multisensory processing in migraine

• Applicant: Privatdozent Dr. Jan Mehnert
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514034845

Heightened sensory perception is, next to headache, the core symptom of migraine. Recent research further suggest an altered neuronal processing of multisensory stimuli already in the interictal phase of migraine. This interruption of multisensory integration can be considered as a cause for the development of migraine attacks. We developed and performed pilot testing of an experimental design including simultaneous time- and frequency-modulated input from multiple sensory modalities (auditory, visual, and painful) to analyze differences in neuronal processing between migraine patients and healthy controls. In order to be able to separate the simultaneous input of the different sensory modalities, they will be repeated with specific frequencies and additionally modulated by changing the intensity simultaneously over time. The former allows the analysis of frequency bands in a time-frequency analysis, each representing a specific sensory modality. The latter leads to the perception of a synchronicity of the multisensory input. A pilot data set by the applicant confirms the feasibility of this approach.Electroencephalography (EEG) from 34 interictal migraineurs and 34 healthy control subjects will be compared to evaluate temporal dynamics with high accuracy. The specificity of the trigeminal system in altered multisensory pain processing is controlled by also applying nociceptive input to the volar forearm. In addition, and to control for the specificity of migraine compared to other chronic pain disorders, a group of 34 back pain patients will also be included. Some brain areas, such as the thalamus, hypothalamus, temporal pole and cerebellum are activated during multisensory processing and also seem to play an important role in migraine pathophsiology. To localize and compare multisensory processing, we will collect and analyze data from functional magnetic resonance imaging (fMRI) in an additional series of experiments in the same groups described above.We will use contrast techniques specifically designed for experiments on multisensory integration to analyze data from both imaging techniques. For this purpose, low-intensity and high-intensity time intervals will be contrasted to avoid double-counting the baseline. Since multisensory integration probably does not occur in a single, modality-independent area but rather involves a network, changes in functional connectivity and neuronal coupling will be investigated using newly developed connectivity measures. For fMRI, we developed Partial Similarity, a method to measure direct connectivity between two areas. We will further investigate neuronal coupling in EEG using Multivariate Interaction Measure.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Claus Christian Hilgetag; Professor Dr. Arne May; Dr. Guido Nolte