A multitude of cognitive and physiological disorders have a debilitating impact on the 'quality-of-life' of the affected patient populace. The majority of such patients are unamenable to any form of treatment as first line (drug) and second line (invasive surgeries) treatments fail. Physical means of brain stimulation, known as ‘neuromodulation’, represent a tenable, non-pharmacological means to probe and treat the dysfunctional neural networks that underpin brain disorders through direct control of the circuit activity. Implanted electrodes for deep brain stimulation (DBS) have been used around the world to treat patients with severe movement disorders, such as PD, and affective disorders, such as obsessive–compulsive disorder (OCD). DBS is being investigated as a treatment for neurodegenerative diseases such as Alzheimer’s disease (AD), with early reports showing an increase in the metabolism of brain regions affected. However, the risk from inserting electrodes into the brain makes exploration of different brain targets difficult and limits the therapeutic impact.
Non-invasive cortical stimulation methods, such as transcranial magnetic stimulation (TMS) and sub-threshold transcranial electrical stimulation (TES) have been used in many human clinical investigations, and TMS is approved by the FDA for patients with treatment-resistant depression. Early reports in healthy humans, show that TES and TMS can boost memory and cognition by enhancing specific oscillatory activity such as slow-wave during non–rapid eye movement (NREM) sleep. However, the ability of TMS or TES to directly stimulate deeper brain structures is obtained at the expense of inducing stronger stimulation of overlying cortical areas, the resulting wider stimulation of which may push on the limits of safety guidelines.
The long-term goal of my research is to develop neuromodulatory interventions for neurodegenerative diseases and other brain disorders by pioneering new tools and principles impact the disease pathology via direct modulation of the underlying network activity.
In a paper that we recently published, (Grossman et al., Cell 169.6 (2017): 1029-1041), we reported the discovery of a strategy for sculpting the electric fields so as to enable focal, yet noninvasive, electrical neural stimulation of the brain. We showed that by delivering multiple electric fields to the brain at slightly different kHz frequencies, which are themselves too high to recruit effective neural firing, but for which the difference frequency is low enough to drive neural activity, we can cause neurons to be electrically activated at a focus without driving neighboring or overlying regions. We call this method temporal interference (TI) stimulation, since the interference of multiple electric fields is what enables the focality: neural stimulation will occur only at the region for which the amplitude of the electric field envelope, at the difference frequency, is of great magnitude. We validated the TI stimulation concept via finite element modelling as well as physics experiments, and experimentally verified that neurons in the living mouse brain could follow the interferential electric field envelope, but not the high frequency carrier. We then demonstrated the ability of TI stimulation to mediate activation of hippocampal neurons without recruiting overlying cortical neurons, and steerably probe motor cortex functionality without physically moving electrodes by altering the currents delivered for interference.
I continue to pioneer neuromodulation tools via scientific exploration of common biophysical principles and rules underpinning the neural processing of electromagnetic stimulation, with natural bridges between advanced computational neuroscience and cutting-edge experiments, ranging from a single neuron cell to human behavior. In addition, together with a network of collaborators, I deploy the tools to discover how entrainment of network activity affects key disease drivers.