Events

Despite significant advances in neuromodulation therapies for Parkinson’s disease (PD), gait and balance disturbances remain a major challenge for patients in advanced stages of the disease. These deficits are often refractory to existing treatments; they significantly increase the risk of falls, exacerbate comorbidities, and severely impact independence and quality of life.

Neuromodulation therapies operating in closed-loop have the potential to harness the intrinsic dynamics of dysfunctional neuronal circuits underlying gait and balance, holding promise for more effective improvements in gait impairments. However, stimulation delivery must be controlled in real time and dynamically tuned to the fluctuating state of patients, as well as to task- and context-related constraints encountered in daily life. This requires robust, evidence-based biomarkers capable of informing locomotor activities and deficits.

We are leveraging the neural sensing capabilities of next-generation deep brain stimulation (DBS) neurostimulators, combined with continuous wireless monitoring of locomotor deficits throughout daily life, to identify and map neural and motor biomarkers of locomotor function and dysfunction in real-world settings. We are combining these clinical assessments in patients with experiments in animal models to ground clinical correlations on mechanistic evidence, and we are developing evidence-based neural decoding algorithms capable of robustly predicting gait disturbances and controlling therapies in closed-loop.

In this talk, I will present our latest developments in these areas and discuss how these advancements are enabling the personalization of closed-loop neuromodulation therapies based on brain biomarkers, ultimately improving gait function in individuals with advanced PD.

Ardem Patapoutian, Nobel Laureate in Physiology or Medicine (2021), Professor at Scripps Research, Investigator, Howard Hughes Medical Institute; Presidential Endowed Chair in Neurobiology.

Abstract
Mechanotransduction was perhaps the last major sensory modality not understood at the molecular level. Proteins/ion channels that sense mechanical force are postulated to play critical roles in sensing touch/pain (somatosensation), sound (hearing), shear stress (cardiovascular function), etc.; however, the identity of ion channels involved in sensing mechanical force had remained elusive. The Patapoutian lab identified PIEZO1 and PIEZO2, mechanically activated cation channels that are expressed in many mechanosensitive cell types. Genetic studies established that PIEZO2 is the principal mechanical transducer for touch, proprioception, baroreception, bladder, and lung stretch, and that PIEZO1 mediates blood-flow sensing, which impacts vascular development and iron homeostasis. Clinical investigations have confirmed the importance of these channels in human physiology. Current work in Patapoutian lab continues to explore the role of mechanosensation and interoception in physiology and disease.

This event is part of the Life Sciences Seminar Series and the BMI Distinguished Seminar Series, hosted by the Mackenzie Mathis Lab. The seminar is followed by a coffee break for fellow researchers to connect.