Metabolic-functional coupling of parvalbmunin-positive GABAergic interneurons in the injured and epileptic brain
Parvalbumin-positive GABAergic interneurons (PV-INs) provide inhibitory control of excitatory neuron activity, coordinate circuit function, and regulate behavior and cognition. PV-INs are uniquely susceptible to loss and dysfunction in traumatic brain injury (TBI) and epilepsy but the cause of this susceptibility is unknown. One hypothesis is that PV-INs use specialized metabolic systems to support their high-frequency action potential firing and that metabolic stress disrupts these systems, leading to their dysfunction and loss. Metabolism-based therapies can restore PV-IN function after injury in preclinical TBI models. Based on these findings, we hypothesize that (1) PV-INs are highly metabolically specialized, (2) these specializations are lost after TBI, and (3) restoring PV-IN metabolic specializations can improve PV-IN function as well as TBI-related outcomes. Using novel single-cell approaches, we can now quantify cell-type-specific metabolism in complex tissues to determine whether PV-IN metabolic dysfunction contributes to the pathophysiology of TBI.
A new science of emotion: How brain-mind-body processes form functional neurological disorder
One of the most common medical conditions you’ve (maybe) never heard of – functional neurological disorder – lays at the interface of neurology and psychiatry and offers a window into fundamental brain-mind-body processes. Across ancient and modern times, functional neurological disorder has had a long and tumultuous history, with an evolving debate and understanding of how biopsychosocial factors contribute to the manifestation of the disorder. A central issue in contemporary discussions has revolved around questioning the extent to which emotions play a mechanistic and aetiological role in functional neurological disorder. Critical in this context, however, is that this ongoing debate has largely omitted the question of what emotions are in the first place. This talk first brings together advances in the understanding of working principles of the brain fundamental to introducing a new understanding of what emotions are. Building on recent theoretical frameworks from affective neuroscience, the idea of how the predictive process of emotion construction can be an integral component of the pathophysiology of functional neurological disorder is discussed.
Post-traumatic headache
Concussion (mild traumatic brain injury) affects approximately 50 million people annually. Headache is the most common symptom after concussion and persists in up to 50% of those affected for at least one-year. The biological underpinnings of and the efficacy and tolerability of treatments for post-traumatic headache has historically received little attention. While treatment in clinical practice is mostly directly at the underlying phenotype of the headache, persistent post-traumatic headache is considered to be less responsive to treatments used to treat migraine or tension-type headache. Over the past several years, significant pre-clinical research has begun to elucidate the mechanism(s) involved in the development of post-traumatic headache, and a concerted effort to evaluate the efficacy of selected treatments for persistent post-traumatic headache has begun. This presentation will review the epidemiology, pathophysiology, and emerging data on the prevention and treatment of post-traumatic headache.
From aura to neuroinflammation: Has imaging resolved the puzzle of migraine pathophysiology?
In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.
Migraine Headache: the revolution and its evolution
This seminar will focus on the extraordinary shift in migraine research during the last 4 decades with the discovery of the trigeminovascular system (TVS) and it’s major impact on pathophysiology and treatment. Compelling evidence supporting the importance of TVS, cortical spreading depression and parameningeal inflammation will be explored as will the implications of newly discovered microvascular channels within the meninges on an attack.
New Frontiers in Understanding and Treating Migraine Headaches
In this presentation I will describe how the CGRP project started and culminated in the development of gepants and mAbs for successful therapy. The outstanding question regarding the preponderance of female migraineurs also remains. I will present views on the reason behind this and suggest that understanding the hormonal influence will pave the way to alleviating hormone related migraine.