Cerebro-Cerebellar Networks in Migraine Symptoms and Headache

The cerebellum is associated with the biology of migraine in a variety of ways. Clinically, symptoms such as fatigue, motor weakness, vertigo, dizziness, difficulty concentrating and finding words, nausea, and visual disturbances are common in different types of migraine. The neural basis of these symptoms is complex, not completely known, and likely involve activation of both specific and shared circuits throughout the brain. Posterior circulation stroke, or neurosurgical removal of posterior fossa tumors, as well as anatomical tract tracing in animals, provided the first insights to theorize about cerebellar functions. Nowadays, with the addition of functional imaging, much progress has been done on cerebellar structure and function in health and disease, and, as a consequence, the theories refined. Accordingly, the cerebellum may be useful but not necessary for the execution of motor, sensory or cognitive tasks, but, rather, would participate as an efficiency facilitator of neurologic functions by improving speed and skill in performance of tasks produced by the cerebral area to which it is reciprocally connected. At the subcortical level, critical regions in these processes are the basal ganglia and thalamic nuclei. Altogether, a modulatory role of the cerebellum over multiple brain regions appears compelling, mainly by considering the complexity of its reciprocal connections to common neural networks involved in motor, vestibular, cognitive, affective, sensory, and autonomic processing-all functions affected at different phases and degrees across the migraine spectrum. Despite the many associations between cerebellum and migraine, it is not known whether this structure contributes to migraine initiation, symptoms generation or headache. Specific cerebellar dysfunction via genetically driven excitatory/inhibitory imbalances, oligemia and/or increased risk to white matter lesions has been proposed as a critical contributor to migraine pathogenesis. Therefore, given that neural projections and functions of many brainstem, midbrain and forebrain areas are shared between the cerebellum and migraine trigeminovascular pathways, this review will provide a synopsis on cerebellar structure and function, its role in trigeminal pain, and an updated overview of relevant clinical and preclinical literature on the potential role of cerebellar networks in migraine pathophysiology.