The brain, as an organ, communicates through both chemical and electrical signals. Neurons are various forms of specialized cells characterized by excitability (electrical responsiveness), meaning they can generate an action potential when sufficiently stimulated. An action potential is conducted along the axon of a neuron and ultimately reaches a synapse where neurotransmitters are released. These diffuse across the synaptic gap and bind to receptors on the receiving neuron, thereby increasing or decreasing the likelihood of a new electrical signal. Our psychotropic medications significantly affect neurotransmitters, as well as various types of ion channels, thereby influencing electrical excitability. Examples of the former include antidepressant medications like selective serotonin and/or norepinephrine reuptake inhibitors (SSRI and SNRI). These selectively inhibit the reuptake of neurotransmitters serotonin and norepinephrine in the synapse, thus initially enhancing the corresponding transmission. Valproate, an antiepileptic and mood-stabilizing medicine, is believed to block voltage-gated sodium channels, thereby reducing electrical excitability. There are also more direct ways to influence electrical signaling. Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are two examples where electrical activity is influenced through the skull. Direct stimulation of brain tissue with electrodes through a procedure called deep brain stimulation (DBS) is another method.
The pale cast of thought
Before delving into the depths of the aforementioned methods of influencing the brain's electricity, it is appropriate to take a retrospective look into history. The psychiatric history contains quite a few treatments that we now consider downright barbaric. Insulin was administered to induce patients into a coma due to low blood sugar, nerves were severed through lobotomies, and patients were induced into seizures through either electric shocks or chemicals. This sounds horrifying and was indeed so in certain cases! However, it's essential not to forget that, in many instances (though not all), the intention was to assist severely mentally ill patients. In the 1950s, the first antipsychotic, chlorpromazine, was marketed. This marked the first time that psychotic symptoms in patients with schizophrenia and other psychotic disorders could be treated and reduced. It was a revolution that allowed the closure of many "storm wards" where the most disruptive patients were cared for. Below is an illustration of a so-called asylum.
Regarding seizures, it was noted early on that patients with both epilepsy and schizophrenia seemed to improve during their psychotic episodes if they experienced seizures. Here is a review article on ECT that also includes a historical section. In the first attempts (around the 1930s) to induce seizures, the Hungarian doctor Ladislas J. Meduna used various chemicals, such as camphor. He had observed that patients with epilepsy had more gliosis in the brain post-mortem, and those with schizophrenia had less. This was the rationale for attempting to induce seizures. Of course, such methods would not be sufficient today, but those were the times. Manfred Sakel, an Austrian psychiatrist, instead attempted to induce seizures by putting patients into insulin coma. Both of these methods were relatively ineffective and had many dangerous and unpleasant side effects. Importantly, it's crucial to know that it wasn't random brutality but an attempt, with some empiricism, to create new treatments. Another contributing factor behind these methods was the Nobel Prize-winning Julius Wagner-Jauregg's discovery that tertiary syphilis (dementia paralytica) could be treated with malaria. This might not sound as odd as it seems because malaria is a fever disease that raises body temperature. Syphilis is caused by the spirochete Treponema pallidum, which is killed at higher temperatures. Simultaneously, quinine was available as a treatment for malaria, providing a way out when one wanted to end the treatment. This treatment became obsolete as soon as effective antibiotics were developed, leading to the disappearance of syphilis from psychiatric care.
Unfortunately, these methods were also used on people who did not suffer from the diseases they were believed to cure. This was a time of burgeoning totalitarianism, with Nazism being the worst example. People were tortured and "treated" for their beliefs or origins. For instance, Julius Wagner-Jauregg used electroconvulsive therapy to "treat" soldiers whom he believed were simulating nervous breakdowns. It is said that Sigmund Freud worked to stop legal proceedings after the war to save Julius Wagner-Jauregg's career.
Lobotomy or leukotomy involves surgically cutting nerve fibers, primarily in the frontal lobe, to treat neurological and psychiatric disorders. In 1949, Portuguese neurologist António Egas Moniz received the Nobel Prize for this discovery. The common story of how the discovery came about is that António Egas Moniz attended a lecture on cortical function in primates by an American neuroscientist. After severing nerve fibers in the frontal lobe, one of the animals became noticeably calmer and had fewer outbursts. This was interpreted as the animal becoming calmer and more inhibited. This might be a good description of the entire method, as lobotomy involves a comprehensive impact on the brain, especially the frontal lobe, which can act as an inhibitory force but also affect the individual's entire personality. Lobotomy spread internationally in the 1940s, and in the United States, Walter Jackson Freeman II and James W. Watts traveled around to perform lobotomies in various psychiatric hospitals. They simplified the procedure by using a transorbital approach, using an ice-pick-like instrument to sever frontal nerve fibers through the eye socket, enabling faster and simpler procedures even outside major hospitals.
Eventually, lobotomy was abandoned and replaced by medications. However, some psychosurgery continued, now performed by neurosurgeons and more targeted. In fact, in Sweden, these procedures continued into the 1990s, especially in Umeå (see an article here). One method was capsulotomy, where a small piece of the internal capsule was cut or burned away with an instrument, believed to be affected in conditions like obsessive-compulsive disorder (OCD). In a Swedish follow-up of 25 patients who underwent the procedure for OCD, there was indeed a good effect on OCD symptoms, but at the same time, a significant risk of side effects.
In upcoming sections, I will delve deeper into various forms of brain stimulation!