In 1935 Moniz introduced “leucotomy,” severing white-matter fibers between the frontal lobes and thalamus with a cannula, and reported reduced anxiety and hallucinations in severe schizophrenia and depression. At that time only electroconvulsive and insulin-coma therapies were available, so leucotomy spread rapidly as a groundbreaking psychosurgical method. Yet serious sequelae, such as personality changes and cognitive deficits, soon emerged, and after the 1950s the rise of psychotropic drugs led to its decline. The episode remains a lesson in balancing effectiveness, safety, and ethics in medicine.

Moniz inserted a pick-like instrument (leucotome) through burr holes and radially cut sub-cortical white-matter tracts of the frontal lobes. He hypothesized that psychoses arose from “fixed pathological associations” and that interrupting circuits would block excessive affective input, easing symptoms. Short-term improvement rates of 30–50 % were reported, but complications such as epilepsy, incontinence, and apathy were frequent. The method evolved into Freeman and Watts’s transorbital lobotomy, yet double-blind evaluation proved difficult and reproducibility limited. Today the work is viewed as a historical precursor to deep-brain stimulation and rTMS.

Moniz disrupted corticothalamic loops by excising pre-frontal projecting fibers in the anterior limb of the internal capsule, aiming to desynchronize limbic inputs. His case reports quantified outcomes with the Beck Lethargy Scale and a custom symptom checklist but lacked control groups and statistical tests. Post-mortem verification of lesion extent was limited and later studies showed heterogeneity of actual cuts. By current standards the evidence level is low, yet the concept of sub-cortical white-matter sectioning informed modern psychosurgical procedures such as cingulotomy and capsulotomy. The controversy also catalyzed formalization of informed consent and clinical research ethics.