Developments in the mechanistic understanding and clinical application of deep brain stimulation for Parkinson’s disease

ABSTRACT

Introduction

Deep brain stimulation (DBS) is a life-changing treatment for patients with Parkinson’s disease (PD) and gives the unique opportunity to directly explore how basal ganglia work. Despite the rapid technological innovation of the last years, the untapped potential of DBS is still high.

Areas covered

This review summarizes the developments in the mechanistic understanding of DBS and the potential clinical applications of cutting-edge technological advances. Rather than a univocal local mechanism, DBS exerts its therapeutic effects through several multimodal mechanisms and involving both local and network-wide structures, although crucial questions remain unexplained. Nonetheless, new insights in mechanistic understanding of DBS in PD have provided solid bases for advances in preoperative selection phase, prediction of motor and non-motor outcomes, leads placement and postoperative stimulation programming.

Expert opinion

DBS has not only strong evidence of clinical effectiveness in PD treatment but technological advancements are revamping its role of neuromodulation of brain circuits and key to better understanding PD pathophysiology. In the next few years, the worldwide use of new technologies in clinical practice will provide large data to elucidate their role and to expand their applications for PD patients, providing useful insights to personalize DBS treatment and follow-up.

KEYWORDS:

• Adaptive stimulation
• connectomics
• deep brain stimulation
• directional stimulation
• early stimulation
• Parkinson’s disease

Article highlights

• Deep brain stimulation (DBS) represents a standard of care for people with Parkinson’s disease (PD) and a powerful tool to investigate PD pathophysiology, enabling the direct observation of basal ganglia networking activity.

• Over the last years, the hypotheses on the mechanistic effects of DBS have undergone a paradigm shift toward a circuital modulation of large-scale brain networks.

• A deeper knowledge of local field potentials and connectomics has provided solid bases for advances of technologies and clinical applications of DBS.

• Growing data deriving from clinical practice on people with DBS, together with genetic, neurophysiologic and radiologic findings, have offered new insights in the critical step of patients’ selection for surgery.

• The correct timing of DBS in PD has been recently redefined, anticipating surgery before reaching severe impairment of social and occupational functioning.

• The large amount of new information, sensed by cutting-edge DBS devices, calls for integrative systems aiming to provide preoperative and postoperative decision-making algorithms helpful for clinicians.

• Future studies will elucidate the impact of the new technologies on postoperative management of PD patients and whether they will definitely improve DBS outcomes.

Declaration of interest

E. Moro has received honoraria from Medtronic, Abbott, and Kyowa for consulting services. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.