This chapter reviews advances in deep brain stimulation (including MRI-based connectomics and closed-loop neurophysiology) and low-intensity focused ultrasound neuromodulation, covering mechanisms, transducer and skull-correction hardware, and early clinical studies toward biomarker-guided…

Relevant to Parkinson's therapeutics because it outlines actionable technological and translational pathways to refine DBS and develop a non-invasive TUS analogue that could expand treatment options, improve targeting, and enable biomarker-driven clinical trials.

The translation of experimental brain stimulation procedures to clinical practice remains a significant challenge. In the present book chapter we review emergent innovations that have recently surfaced or are imminent to make the leap, improving the treatment of patients with brain disorders. We focus on two domains of accelerated innovative potential in both invasive and non-invasive brain stimulation domains. First, current advances in deep brain stimulation (DBS) methodology are introduced. DBS is an established treatment for neurological disorders such as Parkinson's disease, essential tremor and dystonia. Emerging technological advances focusing on when and how to stimulate allow for an extension and refinement of DBS promising scientific and clinical breakthroughs. We reflect on the unprecedented opportunities that MRI-based connectomics and neurophysiology based closed-loop DBS provide for patients with movement disorders, epilepsy and neuropsychiatric diseases. Next, we explore low-intensity focused transcranial ultrasound stimulation (TUS) as an emergent non-invasive neuromodulation technique. Unlike electrical or magnetic methods, TUS combines millimeter spatial precision with the ability to reach deep brain targets, making it the closest non-invasive analogue to DBS. We summarize its candidate mechanisms of action, highlight advances in transducer hardware and skull aberration-correction strategies, and review early clinical studies across movement disorders, epilepsy, pain, and psychiatric indications. Together, these developments illustrate how TUS is progressing from proof-of-concept experiments toward biomarker-guided therapeutic protocols. In conclusion, this chapter provides an outlook on the future of invasive and non-invasive techniques, emphasizing the need for continued research and innovation to overcome challenges in translating experimental successes into effective clinical therapies.