The field of neuromodulation encompasses a wide spectrum of interventional technologies that modify pathological activity within the nervous system to achieve a therapeutic effect. Therapies including deep brain stimulation (DBS), intracranial cortical stimulation (ICS), transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS) have all shown promising results across a range of neurological and neuropsychiatric disorders. While the mechanisms of therapeutic action are invariably different amongst these approaches, there are several fundamental neuroengineering challenges that are commonly applicable to improving neuromodulation efficacy. This article reviews the state-of-the-art of neuromodulation for brain disorders and discusses the challenges and opportunities available for clinicians and researchers interested in advancing neuromodulation therapies.

The system identification framework with the new BN-modulated waveform and the clinical HIL simulation testbed can help develop future model-based closed-loop electrical brain stimulation systems for treatment of neurological and neuropsychiatric disorders.

Chronic pain patients receive escalating opioid dosage prior to SCS implant, and high-dose opioid usage is associated with an increased risk of explant. Neuromodulation can stabilize or decrease opioid usage. Earlier consideration of SCS before escalated opioid usage has the potential to improve outcomes in complex chronic pain.

While beta oscillations often occur within the parkinsonian basal ganglia, how these oscillations emerge from a naive state and change with disease severity is not clear. To address this question, a progressive, nonhuman primate model of Parkinson's disease was developed using staged injections of MPTP. Within each parkinsonian state (naive, mild, moderate, and severe), spontaneous local field potentials were recorded throughout the sensorimotor globus pallidus. In the naive state, beta oscillations (11-32 Hz) occurred in half of the recordings, indicating spontaneous beta oscillations in globus pallidus are not pathognomonic. Mild and moderate states were characterized by a narrower distribution of beta frequencies that shifted toward the 8 -15 Hz range. Additionally, coupling between the phase of beta and the amplitude of highfrequency oscillations (256 -362 Hz) emerged in the mild state and increased with severity. These findings provide a novel mechanistic framework to understand how progressive loss of dopamine translates into abnormal information processing in the pallidum through alterations in oscillatory activity. The results suggest that rather than the emergence of oscillatory activity in one frequency spectrum or the other, parkinsonian motor signs may relate more to the development of altered coupling across multiple frequency spectrums.