One of medicine’s oldest ambitions has been to influence the human mind quickly and effectively. Today, we call this neuromodulation — the ability to alter brain activity and chemistry, usually to relieve symptoms of mental illness or neurological disease.

Long before modern psychiatry existed, doctors experimented with surprisingly primitive methods. In ancient and medieval times, patients suffering from agitation, psychosis, or severe emotional distress were often wrapped in cold blankets, restrained, or subjected to vigorous massage. These treatments occasionally calmed patients temporarily, but their effects were limited and poorly understood.

As desperation for more effective therapies grew, medicine entered a darker and more controversial era: the age of the lobotomy.

The procedure involved inserting a sharp instrument through the thin bone behind the eye socket and into the frontal regions of the brain, particularly areas involved in personality, emotion, and behaviour. Some patients became quieter and less distressed after the operation, which at the time was interpreted as success. However, the cost was often devastating. Many patients experienced profound personality changes, emotional blunting, disability, infection, bleeding, or even death. What was intended as treatment frequently came at the expense of the very qualities that made a person who they were.

Faced with these consequences, physicians searched for alternatives that were less invasive. Attention shifted from physically altering the brain to changing the body’s chemistry.

Two unusual therapies emerged during the early 20th century. One was malaria inoculation therapy, in which patients were intentionally infected with malaria to induce high fevers and lethargy. This was mainly used for neurosyphilis, a devastating brain infection common before antibiotics. Another approach was convulsive therapy, based on observations that some psychiatric symptoms appeared to improve after seizures.

The challenge, however, was how to induce seizures safely and consistently.

Early attempts were crude. Hungarian psychiatrist Ladislas Meduna experimented with camphor injections to provoke seizures; the same caustic substance that gave our medicated oil for insect bites its pungent aroma. Others developed insulin shock therapy, where patients were given massive doses of insulin until dangerously low blood sugar triggered convulsions. While some patients appeared to improve, these methods were unpredictable and carried serious risks, including coma and death.

Then came a turning point: electroconvulsive therapy, better known as ECT.

Few psychiatric treatments have been as misunderstood in popular culture. Films often portray ECT as a brutal punishment involving screaming patients and sadistic doctors. In reality, modern ECT is a carefully controlled medical procedure performed under general anaesthesia with muscle relaxants. Patients do not feel pain during the treatment.

ECT works by delivering a brief, controlled electrical stimulus to the brain, producing a therapeutic seizure lasting less than a minute. Unlike earlier methods, the electrical dose can be precisely adjusted, allowing doctors far greater control and safety.

Today, ECT remains one of the most effective treatments for severe depression, particularly when accompanied by suicidal thinking, psychosis, or refusal to eat and drink. It is also used in severe mania and certain forms of catatonia. For some patients who have not responded to medication, ECT can be lifesaving.

Modern neuromodulation has continued to evolve far beyond ECT. Newer techniques such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation aim to influence brain circuits with increasing precision and fewer side effects. Some have strong scientific evidence, while others remain experimental.

Among modern forms of neuromodulation, vagus nerve stimulation (VNS) is perhaps one fascinating approach. The vagus nerve serves as a major communication highway between the brain and organs such as the heart, lungs, and digestive tract, helping regulate stress, mood, and bodily calmness. This connection is familiar to many people: anxiety may cause a racing heartbeat, “butterflies” in the stomach, nausea, retching, or excessive belching. Recognising this intimate brain–body relationship, scientists proposed an alternative approach to neuromodulation — instead of directly stimulating the brain through invasive procedures, why not influence it indirectly through the vagus nerve as a biological “proxy”?

In VNS, a small pacemaker-like device is implanted beneath the skin of the chest, with a wire attached to the vagus nerve in the neck. The device delivers gentle electrical pulses that modulate brain circuits involved in mood and seizure control. Originally developed for epilepsy, clinicians later observed that some patients also experienced improvement in severe depression, although the evidence for its antidepressant effects remains modest. 

Deep brain stimulation (DBS) is a surgical treatment that involves implanting small electrodes into specific areas of the brain. While it sounds dramatic, it’s increasingly being used for conditions that don’t respond to standard therapies.

The electrodes are placed in the basal ganglia; a cluster of structures deep in the brain that help control movement. For decades, DBS has been used to manage Parkinson’s disease symptoms. But researchers have since discovered that these same brain circuits also play a role in regulating emotions, including the intrusive thoughts and compulsive urges seen in obsessive-compulsive disorder (OCD).

By delivering carefully controlled electrical impulses, DBS can help interrupt the faulty signals driving these distressing symptoms. Different surgical teams target slightly different brain regions—some focus on an area called the nucleus accumbens, which is involved in reward and motivation, while others target the bed nucleus of the stria terminalis, a structure linked to anxiety responses.

In Australia for example, the Royal Melbourne Hospital offers a comprehensive DBS program. Patients undergo thorough assessment by neurologists and neuropsychiatrists to determine whether they’re suitable candidates for the procedure.

Once the device is implanted, it can be adjusted remotely by the medical team. Some patients who become skilled at recognising their own symptoms are even taught to fine-tune the stimulation themselves—giving them a greater sense of control over their condition.

Early results have been promising, though DBS for OCD remains a specialised option typically reserved for severe cases that haven’t improved with other treatments.

While some of the previously discussed procedures require surgery to implant electrodes into the brain, there are also less invasive forms of neuromodulation used in mental health treatment. Two such examples are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These therapies aim to alter patterns of neural activity in the brain in order to achieve therapeutic effects, without the need for surgery.

TMS works by delivering magnetic pulses through a coil placed externally against the scalp. Before treatment begins, clinicians typically identify the patient’s motor cortex by stimulating different regions of the scalp until a small twitch is observed in the fingers or arm. Once this area has been localised, the coil can then be positioned slightly forward to target brain regions involved in mood regulation, anxiety, obsessive-compulsive disorder, and other psychiatric conditions. The patient would be advised strongly against irregular caffeine intake or use of sedatives as these treatment points interestingly tends to ‘wander’ away when stimulating or sedating agents are used.

Advances in TMS technology have also allowed clinicians to tailor the frequency and pattern of magnetic stimulation into different treatment protocols. As a result, TMS is now used in a growing range of conditions, including severe depression, anxiety disorders, stress-related symptoms, and sleep disturbances. Depending on the treatment protocol and clinical indication, sessions generally last between 40 minutes and one hour.

tDCS, or transcranial direct current stimulation, is another non-invasive form of brain stimulation therapy. Unlike TMS, which uses magnetic pulses to stimulate specific brain regions, tDCS delivers a very small electrical current through electrodes placed on the scalp. The current itself is mild and usually does not directly trigger neurons to fire. Instead, it changes how easily certain brain cells communicate with each other, making areas of the brain either more or less active depending on the treatment aim.

A typical tDCS session involves placing two small sponge-covered electrodes on different parts of the head. Most patients describe the sensation as a mild tingling, itching, or warmth on the scalp during the first few minutes of treatment. Sessions are generally shorter than TMS, often lasting around 20 to 30 minutes, and are usually repeated over multiple days or weeks to achieve sustained benefit.

Researchers are currently exploring the use of tDCS in conditions such as depression, chronic pain, anxiety disorders, stroke rehabilitation, and cognitive difficulties. Because the electrical current used is low in intensity, tDCS is generally considered safe and well tolerated, with side effects commonly limited to temporary skin irritation or mild headache. Although its effects may be more subtle compared to TMS, tDCS has gained attention because of its portability, lower cost, and relative ease of administration.

In an effort to reduce the need for invasive brain procedures, modern neuromodulation research has increasingly shifted towards targeting nerves outside the brain as a way of indirectly influencing the central nervous system. This concept has led to the development of therapies such as peripheral nerve stimulation and auricular nerve stimulation. Rather than placing electrodes directly into the brain, these approaches aim to send therapeutic signals through nerves that communicate closely with brain networks involved in mood, stress, pain, and emotional regulation.

Auricular nerve stimulation focuses on nerves located around the outer ear. Small electrodes are placed on the surface of the ear to deliver gentle electrical stimulation to branches of nerves, including parts of the vagus nerve, which has widespread connections throughout the brain and body. If the VNS stimulation discussed earlier requires an implantable node to deliver stimulus, the auricular path offer an alternate route; further away, but bypassing the need for surgery. 

Because the ear provides a relatively accessible pathway to these neural circuits, researchers have explored its use in conditions such as post-traumatic stress disorder (PTSD), anxiety disorders, migraine, chronic pain, and stress-related symptoms. Treatment is generally non-invasive and well tolerated, with patients often experiencing only mild tingling or warmth during stimulation.

Peripheral nerve stimulation works on a similar principle but targets nerves elsewhere in the body, such as those in the face, neck, or limbs. By stimulating these nerves, clinicians hope to influence brain activity involved in pain processing, emotional regulation, attention, and mood. Unlike traditional psychiatric treatments that act through medication circulating throughout the body, these therapies attempt to modulate specific neural pathways more directly.

Although both auricular and peripheral nerve stimulation remain largely experimental in mental health treatment, early research has shown promising results, particularly for milder psychiatric conditions and stress-related disorders. Their appeal lies in being less invasive, relatively safe, and potentially more accessible compared to surgical neuromodulation procedures. As technology and research continue to advance, these therapies may become increasingly important as part of a broader range of treatment options for mental health disorders.

This article is authored by Dr Chong Siew Koon, Clinical Fellow of Neuropsychiatry, Hospital Kuala Lumpur, and Dr Ong Wan Xi, Psychiatrist, Hospital Bahagia Ulu Kinta.