Neuromodulation: Current Practice, Limitations, and Considerations

Right now, signals from your brain are instructing the muscles around each eye to contract, panning your view left to right and adjusting focus along the way. The photoreceptors in your eyes react to the photons reflecting off each letter, ultimately transmitting information through the optic nerve, back to the primary visual cortex, where they are translated into meaning. Although it goes mostly unnoticed, your nervous system is constantly hard at work.

In their simplest form, every function of the human body can be reduced to a series of electrochemical reactions in the nervous system. Whether you are reading this page, lifting your cup of coffee, feeling that you ate too much for breakfast, or recognizing the song playing on the radio, all can be traced back to the amazing, complex network of electrical connections and chemical reactions that is the human nervous system. The sensations we feel every day and how our body reacts to them are the result of thousands of receptors talking to each other. And now, scientists are getting in on the conversation.

Neuromodulation (or neurostimulation) is the application of electrical signals to promote, inhibit, or otherwise change neural behavior. Alan Lloyd Hodgkin and Andrew Huxley famously showed how nerves communicate through electrical impulses known as action potentials in 1952 (and won the Nobel Prize for their work a decade later). When a substantial electric potential builds up around a nerve, the nerve produces an impulse that travels to the end of the nerve cell body, where it connects with another cell via an electrical or chemical synapse. The action potential from one nerve can induce a similar potential in another nerve, allowing communication between cells. Sometimes this connection tells a muscle to contract. Other times, it relays sensory information back to the brain. However, these nerves can’t distinguish between an electrical signal from their neighbor and an electrical signal from an implanted electrode. These artificial signals provide an interface to communicate with the nervous system. As we learn more and more about the way nerves communicate and the pathways they exhibit, we can tailor our electrical impulses to speak the body’s natural language.

Electricity has actually been applied therapeutically for centuries, but not nearly as elegantly as implied above. In fact, the perception most have of electrotherapy is likely electroshock or electroconvulsive therapy, where electricity is broadly administered to the brain to treat psychiatric disorders. The kind of modulation detailed in this article is a very precise and targeted application, and unlike pharmaceuticals, it works with how the body functions naturally.

Traditional pharmaceuticals work by binding to molecules and disrupting the natural responses of the body. For example, aspirin produces an analgesic effect by inhibiting a specific enzyme in the inflammatory pathway. Without this enzyme, the body cannot release the molecules needed to signal pain and an inflammatory response. Pharmaceuticals are remarkable at treating the condition for which they are indicated. However, most of these drugs are administered system-wide, either orally or intravenously, and end up circulating through the bloodstream. What happens when the molecule itself causes unwanted side effects? Or achieving the desired effect in one location leads to an undesired effect in another (think blood thinners and internal bleeding)? Patients (and physicians) often assume pharmaceuticals to be the best treatment because they are a product of years of research at billion-dollar companies, but the list of side effects in any pharmaceutical commercial takes up half of the ad time.

Neuromodulation offers a level of specificity and sensitivity that pharmaceuticals can’t match. Rather than engineering a foreign molecule aimed at disrupting the natural processes of the body, it uses a language the body readily understands to provide a safe and effective therapy for all users.

Neuromodulation and Neurostimulation in Practice

Just as the nervous system uses these electrical signals to control every bodily function, scientists have tapped into these pathways to treat a wide variety of conditions. Though neuromodulation provides opportunities to tackle an endless number of conditions, we will focus on stimulation using electricity. Using the interplay between electricity and magnetism, many companies are using the latter as a modality for therapy. The underlying concept of producing an electrical field remains the same, but is beyond the scope of this piece.

In cases of intractable, neuropathic pain, spinal cord stimulators have proven to be successful in treating symptoms that are resistant to even the strongest pharmaceuticals. The device consists of a small electrical generator positioned in the lower back and a collection of leads that hardwire the electrode directly to the nervous tissue in the spine. The device delivers small electrical currents that provide relief by blocking transmission of pain signals from the extremities up to the brain.

Instead of inhibiting neural activity, functional electrical stimulation (or FES) systems apply electricity to stimulate the motor neurons of muscles that are impaired by lesions in the central nervous system. These are muscles that are otherwise paralyzed by stroke, spinal cord injury, or traumatic brain injury. Even though the neural connection to these muscles has been disrupted, they remain healthy for some time after injury and can be stimulated artificially. FES has been used to allow individuals with paraplegia to stand and even walk when given appropriate upper body support. When the lesion is present higher in the spinal cord, even vital organ function can be disrupted. In these cases, FES has restored bladder and bowel control and phrenic nerve stimulation can control respiration.