The term "psychosis" itself was first introduced by Karl Friedrich Canstatt, who used it as a shortened form of "psychic neurosis," at a time when neurosis referred broadly to any disease of the nervous system.

Studying these ancient descriptions of what we now know as psychosis is imperative to the progression of treatment for disorders that have psychoses as one of the symptoms.

Many of these were considered "heroic therapies" due to their invasive nature and questionable effectiveness. While psychoanalytic approaches were also attempted, their impact on treating psychosis was largely limited.

In the 1930s, Manfred Sakel in Vienna introduced hypoglycemic coma therapy, using insulin injections as a treatment for schizophrenia. Around the same time, Ladislav von Meduna, a Hungarian physician, developed seizure therapy using intravenous cardiazol, primarily for depressive states. However, this method was abandoned in 1938 when Italian researchers Cerletti and Bini introduced electroconvulsive therapy (ECT) for severe mental disorders. Initially used for schizophrenia, ECT quickly became more commonly applied to severe depression. Effective tranquilizers with lasting effects did not emerge until 1952, when French researchers Delay and Deniker introduced chlorpromazine, the first neuroleptic drug, belonging to the phenothiazine class.

Studying these early, more controversial and less humane, treatments is important to the history of neuroscience as researchers strive to develop more humane treatments for a variety of mental illnesses, including those that have psychoses.

The Moral Treatment Movement was brought about after Dorothea Dix exposed the harsh realities of early American society’s treatment of the mentally ill and educated the public about a more compassionate approach she had encountered during her extensive travels. While many influential figures contributed to the establishment of asylums in the 19th century, it was Dix who successfully persuaded state legislatures to fund them. Through her efforts, she rescued countless individuals with severe mental illness from neglect and inhumane conditions. Her mission remains especially relevant today, as society faces challenges similar to those she sought to address.

In the early United States, mental health care was virtually nonexistent. Families were expected to confine mentally ill relatives to prevent them from disrupting society, often isolating them in attics, cellars, or shacks. This approach echoed beliefs from Ancient Greece, where Plato wrote in The Laws: “If someone should be mad, he is not to appear openly in the city. The relatives in each case are to guard the persons in their homes.”

Studying the Moral Treatment Movement contributes to the history of neuroscience because increasing the humanity of treatment of the mentally ill allows for more progression of treatment for different mental illnesses.

people experiencing psychosis were often socially isolated from their communities and confined to asylums or prisons. Herbal remedies could also be used in certain communities to calm certain psychotic behaviors. A good example of this is the use of medicinal plants by the traditional medical practitioners of Rangamati district in the Chittagong Hill Tracts (CHT) region of Bangladesh for the treatment of schizophrenia-like psychosis; this practice is still ongoing today for some diseases.

Studying these ancient treatments is important to the history of neuroscience because it allows us to further examine what treatments became obsolete over time, which can help to refine current treatments for different disorders.

Burkhardt's topectomy method involved removing certain small areas of cortical tissues in specific cortical areas based on the symptoms a patient would present with. For example, one patient had, "Irritability and changes in her mood. As fast as lightning, from the smallest cerebral event, be it of sensorial or intellectual in origin, there develops an increase or a change likewise quickly to violent events" (Manjila et al, 2008). So, Burkhardt decided to remove a small strip of tissue between the posterior and anterior components of the language system—the associations between sensory and motor areas. Immediately after the operation, the patient continued to hallucinate and experience mood changes; 8 months later, she had no visual or auditory hallucinations and the impulsiveness and agitation had also improved as well. Another case involved Burckhardt resecting a small part of the Wernicke's area in one patient who, "developed auditory hallucinations, mood swings from agitation to depression, and suicidal ideations" (Majila et al, 2008). The patient's mother described his demeanor post-operation as being docile, and quiet, and muted almost.

Topectomies in general for treating schizophrenia in the 19th century are important to the history of neuroscience because it is a pivotal example of how treatment was focused on only removing the symptoms of this mental disorder, not addressing the root cause, in an invasive way. This could be one of the driving influences for Egas Moniz to develop the the leucotomy for psychosis treatment

At this point in history, there was no specific antipsychotic medication for schizophrenic patients, or those with any other disorders that caused psychosis. Barbituates were also used for the same reasons during the end of the 19th century. In fact, the Swiss psychiatrist Jakob Klaesi used a barbiturate called somnifen in the 1920s for a special type of sleep therapy he developed for schizophrenic patients.

Insulin coma induction would still be used in the late 19th century to early 20th century. Drug treatment before Moniz's leucotomy technique was used in broad ways, not targeting specific dopamine receptors like today's modern antipsychotic drugs do today.

Acknowledging and studying these first drug treatment attempts is important to the history of neuroscience because it allowed researchers down the line to create more specific drug treatments.

Moniz was inspired by a 1935 presentation at the Second International Congress of Neurology in London, which described a chimpanzee that became more cooperative after its frontal lobes were removed. He also took into account clinical reports of patients who underwent frontal lobe surgery and experienced personality changes.

Moniz theorized that abnormal neural connections in the frontal lobes contributed to mental illness. In the 1930s, he and his colleague Almeida Lima developed the leucotomy procedure in Lisbon, Portugal. However, Moniz cautioned that leucotomy was a radical treatment that should only be used when other methods had failed. Moniz believed that individuals with obsessive and melancholic tendencies could benefit from the removal of their frontal lobes. To perform the leucotomy, he collaborated with Almeida Lima to design a needle-like instrument equipped with a retractable wire loop for the procedure.

Although the procedure gained widespread popularity, its use declined in the 1950s following the introduction of tranquilizing or antipsychotic drugs, which offered a less invasive approach to treating mental illness.

The intentions behind creating the lobotomy procedure, with Moniz cautioning that it should only be used when all other methods fail, is important to note historically. This is because over time, the lobotomy was used for less severe mental illnesses, both with the surgical procedure and the use of the lobotomy-like drugs; this completely deviated from Moniz's warning.

The origins of surgical approaches for treating neuropsychiatric disorders date back to Swiss psychiatrist Gottlieb Burckhardt in 1881, when he performed surgery on six patients experiencing hallucinations and behavioral disturbances. While some showed improvement, the procedure also resulted in serious complications. Due to the controversial and incomplete results, Burckhardt faced rejection from the medical community, leading to a long dormancy in the field of surgical psychiatry until 1935. That year, Fulton and Jacobsen conducted experiments on two primates exhibiting neurotic behaviors, surgically separating their frontal lobes, which led to marked symptom improvements.

Building on these findings, Egas Moniz observed that psychoses such as schizophrenia and severe paranoia involve persistent thought patterns that disrupt normal psychological function. He hypothesized that cutting the nerve fibers between the frontal lobes and the thalamus could help realign these dysfunctional patterns. In 1936, Moniz and Almeida Lima performed the first prefrontal leucotomy (later known as lobotomy), initially using alcohol injections to destroy white matter in the frontal lobes. Moniz later refined his technique with a leucotome, a surgical instrument that allowed for precise cuts in the white matter of each hemisphere. Early results showed some promise, with a few patients experiencing notable improvements.

This experimental process to find the perfect lobotomy procedure is an integral part of neuroscience history because it marks an important milestone in psychiatric surgery.

The frontal lobe was studied because Moniz theorized that severing the nerve fibers connecting the frontal lobes to the thalamus could improve symptoms of mental illness. The frontal lobes, located behind the forehead, play a key role in speech, movement, decision-making, and personality.

The thalamus was studied because as the brain’s sensory relay center, the thalamus processes and transmits sensory impulses. Moniz believed that disrupting its connection to the frontal lobes could alter dysfunctional thought patterns.

Moniz's procedure, specifically called the prefrontal leucotomy, was used to treat severe mental illnesses such as schizophrenia, depression, and obsessive-compulsive disorder (OCD). Although widely practiced in the 1940s and 1950s, it became highly controversial and is now considered unacceptable. The use of lobotomies declined significantly with the introduction of psychiatric medications, most notably the development and availability of cholorazopine.

This is important to neuroscience history because at this point we now know which specific brain areas contribute to psychoses and can be altered to relieve symptoms of things like schizophrenia.

Intended Benefits:

• Reduced tension and agitation

• Made patients calm and docile

• Allowed some patients to reintegrate with their families

Negative Consequences:

• Apathy, passivity, and lack of initiative

• Poor concentration and attention span

• Diminished emotional depth and intensity

• Reduced spontaneity, responsiveness, self-awareness, and self-control

• Emotional blunting and restricted intellectual capacity

• Some patients became more outspoken or experienced mood swings

Many lost the ability to feel emotions

Some became catatonic, and a few died as a result of the procedure

Studying the symptoms allows neuroscientists to learn the history of psychiatric surgery, especially the lobotomy as it's an important part of psychiatric surgery, and aid in the development of better surgical techniques.

For major depressive disorder (MDD), vagus nerve stimulation (VNS) is used as a treatment. Similar to DBS, it involves an implantable device that delivers mild, pulsed electrical signals to modify neuronal firing patterns and brain activity associated with depression.

Candidates for these procedures are individuals who have suffered from OCD or treatment-resistant depression for at least five years and have exhausted all standard treatment options without improvement. The screening process includes a comprehensive assessment of the patient’s current symptoms and mental health history.

Following surgery, hospital recovery typically lasts one to two days, followed by a few weeks of at-home rest. These therapies do more than just manage symptoms—they enhance patients’ responsiveness to other medications and psychological treatments, making previously ineffective approaches more beneficial.

Additionally, modern MRI-guided stereotactic techniques are now available for psychiatric treatments. These include bilateral anterior cingulotomy, as well as an extended version known as bilateral extended cingulotomy, which can be followed by staged limbic leucotomy (LL).

Other ablative surgeries for psychiatric disorders, such as subcaudate tractotomy (SCT) and anterior capsulotomy (AC), utilize advanced MRI-guided techniques or radiosurgical capsulotomy for precise targeting.

Additionally, emerging research explores the potential of MR-guided focused ultrasound (MRgFUS) as a non-invasive treatment for major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).

This is relevant to the history of neuroscience because these techniques are now very specific to a certain mental illnesses, focused on limiting negative side-effects.

• Affiliation at the time of award: University of Lisbon & Neurological Institute, Lisbon, Portugal

• Prize Motivation: "For his discovery of the therapeutic value of leucotomy in certain psychoses."

• Prize Share: 1/2

Egas Moniz observed that certain psychoses, particularly schizophrenia and severe paranoia, involve persistent thought patterns that overpower normal psychological functions. He theorized that cutting the nerve fibers between the frontal lobes—which play a key role in psychological responses—and the thalamus, a central relay for sensory impulses, could potentially disrupt these patterns and promote more typical cognitive function.

For optimal mental well-being, nerve impulses in the brain must function properly. In the mid-1930s, Egas Moniz introduced lobotomy (also called the leucotomy), a surgical procedure that involved cutting into the prefrontal lobe to alleviate severe symptoms of serious mental illnesses. This procedure became widely used in the 1940s and 1950s but was soon found to cause significant personality changes in many patients. The practice declined sharply in the 1950s with the development of medications for mental illness, which provided a less invasive and more effective alternative.

Egas Moniz was also involved in politics. Between 1903 and 1917, he served multiple terms in the Portuguese Chamber of Deputies, held the position of Portuguese minister in Madrid (1917–1918), and led Portugal’s delegation at the Paris Peace Conference (1918–1919).