PO-69 | Three-month atogepant treatment modulates dopaminergic-related functional connectivity in episodic migraine

Davide Fedeli,¹ Danilo Antonio Montisano,¹ Greta Demichelis,¹ Giuseppe Ciullo,^1,2 Jean Paul Medina Carrion,¹ Maria Grazia Bruzzone,¹ Emilio Ciusani,¹ Alessandra Erbetta,¹ Marina Grisoli,¹ Erika Guastafierro,¹ Domenico D’Amico,¹ Alberto Raggi,¹ Anna Nigri,¹ Licia Grazzi¹ | ¹Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; ²University of Parma, Parma, Italy

Background: Episodic Migraine (EM) is a highly prevalent neurological disorder. Recent therapeutic advances have targeted the calcitonin gene-related peptide (CGRP), a neuropeptide implicated in migraine pathophysiology. Promising results have been obtained with a new class of drugs consisting of small-molecule CGRP receptor antagonists, known as gepants, potentially capable of crossing the blood-brain barrier. Atogepant, an oral anti-CGRP, is effective in EM prevention, yet its effects on central brain activity and neurotransmitter circuits remain largely unclear. This study investigates brain functional connectivity changes related with key neurotransmitter systems, following three months of treatment with Atogepant in a group of EM patients.

Methods: Fifteen adult EM patients underwent clinical assessments and resting-state functional MRI before treatment and after 3 months of daily Atogepant 60mg administration. Functional connectivity analyses were performed within the novel neurotransmitter-related functional connectivity framework (REACT) to investigate longitudinal connectivity changes associated with the distribution of serotonin, noradrenaline, mesocorticolimbic and nigrostriatal dopamine.

Results: Following 3 months of Atogepant treatment, headache frequency reduction was observed in all patients. Moreover, patients exhibited increased functional connectivity at follow-up within the mesocorticolimbic dopaminergic system (D1 receptor and DAT transporter), in the medial orbitofrontal cortex.

Conclusion: Atogepant treatment is associated with neurotransmitter-related functional connectivity changes within the dopaminergic system and reduced headache frequency in EM patients. Such findings highlight the potential involvement of central neurotransmitter systems in EM pathophysiological processes influenced by preventive migraine treatments. A deeper understanding of these central changes could provide valuable insights into EM and its therapeutic targets.