Emerging therapies for neuromodulation in Parkinson's disease

Parkinson's disease is characterized by its cardinal motor symptoms: bradykinesia, rigidity, tremor, and postural instability. The underlying physiological dysfunction includes basal ganglia pathways that contribute to both motor and non-motor symptoms. These pathways can be influenced by neural network modulation through the application of electrical or magnetic fields. Neuromodulation therapy can also be used to target symptom-specific networks. Deep brain stimulation (DBS) is an example of an effective neuromodulatory approach, mainly for the treatment of motor symptoms. DBS has evolved over the last three decades through several technological advances including imaging-guided planning, brain leads with sensing capabilities, closed-loop stimulation, and segmented leads with directional steering. Less invasive forms of neuromodulation have also been introduced and these techniques can leverage disease-specific networks through the application of transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsive therapy. Newer approaches have also emerged in the laboratory setting including temporal interference stimulation, low-frequency focused ultrasound, and magnetoelectric stimulation. We will review current and emerging neuromodulation therapies for their potential application to PD.