Our knowledge of the brain gathered pace during the period between Parkinson's "shaking palsy" and Cushing's implementation of groundbreaking neurosurgical techniques—with nosologic, anatomical, surgical, and neurologic advances that reflected the ebullience of the scientific arena.

Attitudes towards the mentally ill were also changing. Dorothea Dix and the asylum movement fought for the humane care of patients in custom-built institutions, and numerous practitioners dedicated themselves to the care of the mentally ill.

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James Parkinson (1755-1824): Depiction of the Shaking Palsy

A physician, pioneering neurologist, geologist, paleontologist, and reformer, James Parkinson was very much a product of the Enlightenment, active during a turbulent time in history and attuned to the medical, social, and political discourses of his age.^[1,2]

Best known for "An Essay on the Shaking Palsy" (1817), the disease which would take his name, Parkinson was a gifted clinician who, after his formal medical training in London, spent his career in the practice founded by his father.

Written before the emergence of neurology as a developed area of study, Parkinson's description of the "shaking palsy" is notably for its continued relevance and insight.^[2] He wrote of "[i]nvoluntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured."^[3]

Outside of medicine, James Parkinson was active in social and political movements as a proponent of universal suffrage and appropriate representation in the House of Commons,^[1] as well as being involved in the welfare of children and the mentally infirm.

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Dorothea Lynde Dix (1802-1887): Advocate for the "Insane," Leader of the American Asylum Movement

The Massachusetts schoolteacher Dorothea Dix dedicated her career to the care of the mentally ill and was directly responsible for the creation of over 30 state hospitals. Equally important, Dix helped alter society's perception of these patients, proposing that the state be morally, medically, and legally responsible for the "insane."^[4,5]

Starting in the 1840s, the asylum movement in the United States sought to extract mentally ill persons from prisons and privately funded institutions and place them in more humane settings within specialized, state-run asylums. Dorothea Dix was a prominent member of the movement—an extraordinary feat at a time when women did not have the vote and were excluded from much of the public arena—and a determined advocate for social reform.

Dix's ideas and influence spread as far afield as the United Kingdom, where she was also an active participant in asylum reform.^[5,6]

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Jean-Martin Charcot (1825-1893): The Father of Modern Neurology

One of the most influential scientists of the 19th century, Jean-Martin Charcot was the first to correlate clinical status with pathologic observations obtained at autopsy—a seemingly obvious connection that was revolutionary at the time. For his extensive contributions to the field and its methodology, Charcot is considered a founding father of neurology.

As a pathologist and chief physician at Salpêtrière Hospital in Paris—a "grand asylum for human misery"^[7]—Charcot was privy to a seemingly never-ending supply of cases that helped provide the building blocks for his anatomoclinical approach to neurology. Charcot's patient files contained detailed clinical descriptions accompanied by pathologic observations, which permitted the precise classification of a wide range of neurologic diseases.^[7-9]

As Charcot gathered international renown, Salpêtrière became an important neurologic center, drawing students from around France and the world—including Sigmund Freud and Georges Gilles de la Tourette—who were attracted by Charcot's original and apparently spellbinding teaching.^[6]

From a humble background, multilingual, erudite, and charismatic, Charcot established neurology as a separate medical specialty and made significant contributions to multiple sclerosis and amyotrophic lateral sclerosis. He was a pioneer in the use of rehabilitation, described the vascular supply to the brain, and differentiated between hysteria and epilepsy and between the tremors in multiple sclerosis vs those in Parkinson disease.^[4,7]

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Pierre Paul Broca (1824-1880): Localization of Cortical Function

Pierre Paul Broca—surgeon and anthropologist—advanced our understanding of language by defining an area of the brain as the region responsible for speech, while developing the term and study of aphasia.^[10]

Although far from the first physician to specialize in language, Broca's casework with patients who had lost their ability to speak coherently, and examinations of their brains after their death, led him to label a region of the frontal lobe—Broca's area—as that associated with speech.

Broca described the loss of articulated speech as "aphemia," dedicating much of his career to studying the conditions later known as "Broca aphasia." He noted the tendency for the condition to improve with therapy and patients to cope better over time, and proposed the concept of brain plasticity as a possible explanation.^[11]

Although the complexity of language is, naturally, better understood now than in Broca's time, his findings remain groundbreaking and his localizing of speech function in the brain fundamental to neuropsychologists, speech therapists and pathologists, neurolinguists, and cognitive neuroscientists.^[12]

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Wilhelm Maximilian Wundt (1832-1920): A Founder of Experimental Psychology

Founded in 1879, the psychology laboratory at the University of Leipzig was a magnet for budding experimental psychologists from around the world and put its creator, Wilhelm Wundt, on the map as one of the founders of experimental psychology.

Wundt—a physician and physiologist, from a family of distinguished academics—was by nature suited to balanced thought and careful experimentation. As such, he appears to have been predisposed to "introspective methodology"—the study of mental processes using experimental and quantitative approaches similar to those used in other realms of scientific research. His thinking was counter to theory of "speculative philosophy," which held traction in psychological research of the time.^[4]

Wundt's research is notable for its examination of perception. His true impact, however, stems from his methodologies and his dedication to training—Emil Kraepelin, for instance, was his student—which helped advance thinking and spawned future generations of academics.

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Emil Kraepelin (1856-1926): Founder of the Modern Method of Psychiatric Nosology

The celebrated German systematist Emil Kraepelin completed his training in both psychology (as a student of Wilhelm Wundt) and psychiatry. He held clinical and research positions, first in Estonia and, as his influence spread, at Heidelberg University. Kraepelin's rigorous methodology, acute sense of observation, and clarity of expression lead to the famous nosology of modern psychiatry.

Throughout his career, Kraepelin kept detailed patient files to document clinical symptoms, prior histories, and outcomes. His insight and organizational prowess extended to his popular published work, and it is argued that his nosology reflects the structure—literally, the table of contents—of his textbooks, such as the Compendium of Psychiatry.^[4]

Judged by some as doctrine-minded and brain-centric, others argue that Kraepelin's approach was equally psychologically inclined and that he was less doctrinaire than history seems to recount.^[13]

Beyond his classifications, among his many achievements, Kraepelin contributed to our understanding of bipolar disorder (relating it to four temperaments: depressive, manic, irritable, and cyclothymic) and dementia praecox. He also used the term "psychopath" as a general descriptor of mental disorders.^[5]

Kraepelin is lauded as one of the most influential physicians in history.

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Santiago Ramón y Cajal (1852-1934): The Architecture of Neurons

For his microscopic studies of the brain and his theory that the nervous system is comprised of billions of separate nerve cells, which lead to the elaboration of the architecture of neurons, the Spanish physician, neurologist, and illustrator Santiago Ramón y Cajal is celebrated as a founding father of neuroscience.^[14]

In 1906, Ramón y Cajal shared the Nobel Prize with Camillo Golgi "in recognition of their work on the structure of the nervous system."^[15] Golgi's novel staining technique (impregnation with silver) provided Ramón y Cajal with the vehicle for his histologic studies of the brain.^[15] Working from the University of Barcelona, and then Madrid, Ramón y Cajal's slides formed the basis for his theory of the contiguous nature of the individual cells in the nervous system, in contradiction to the "continuous hypothesis" proposed by Joseph von Gerlach and supported by Golgi.^[14]

A talented artist, whose drawings are still used to illustrate textbooks, Ramón y Cajal also identified the interstitial cell of Cajal and the axonal growth cone. His life's work helped provide the foundation for modern neuroanatomy.^[14,16]

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Alois Alzheimer (1864-1915): Alzheimer Disease

As a young neuropathologist and psychiatrist, the Bavarian Alois Alzheimer was approached by his boss and mentor, Emil Kraepelin, to help identify a cerebral/histologic substrate for dementia praecox. This collaboration led to Alzheimer discovering histologic abnormalities in a form of dementia that, unsurprisingly, would carry his name.^[5]

In autopsies at the turn of the 20th century, Alzheimer observed widely dispersed neurofibrillary tangles and sclerotic plaques in the upper layers of the cortex in patients who experienced lapses of memory and attentional anomalies progressively leading to disorientation and confusion. He identified the features as differing from senile dementia.^[4,17]

In 1910, the disease was recognized by Kraepelin in his textbook The Handbook of Psychiatry.

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Paul Eugen Bleuler (1857-1939): Elaboration of Schizophrenia

Based on his extensive clinical work, the Swiss psychiatrist Paul Eugen Bleuler conceived "schizophrenia" as a replacement for Kraepelin's dementia praecox.

A contemporary and one-time colleague of Sigmund Freud, Bleuler broke with Freud's school of thought over what he perceived to be its absolutist approach and the exaggerated influence of childhood sexuality.^[5]

Bleuler was a dedicated clinician who spent much time with "psychotic" patients, recording his visits in detailed, meticulously kept records.^[18] He argued that schizophrenia was a grouping in which mild disease does not necessarily progress to more severe versions and which was, to a degree, treatable.^[5,19]

In his description of the "primary signs" of schizophrenia, Bleuler used the term "autism" to relate a state of withdrawal from reality—along with associations, ambivalence, and affect,^[2,19] opening up autism as a field of study and source of debate.^[20]

Bleuler's contributions must be considered in light of his support of the eugenics movement and his advocation for the sterilization of people diagnosed with (or viewed to be predisposed to) schizophrenia.^[21-23]

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Harvey Cushing (1869-1939): Founding Father of Modern Neurosurgery

Often described as the most important surgeon of the 20th century,^[24] the Ohio-born Harvey Cushing was a pioneering neurosurgeon who helped found the specialty and made numerous contributions to surgical techniques and our understanding of the brain.

During his prodigious clinical and academic career, Cushing conducted thousands of brain surgeries, keeping meticulous case records that included specimens, notes, and slides—10,000 to 15,000 of which are housed in the Harvey Cushing Tumor Registry at Yale, a joint collaboration with the neuropathologist Louise Eisenhardt.^[25-27]

Cushing was instrumental in creating and advancing techniques and procedures in operations of the brain and spinal cord. He was also one of the first to consult x-rays before operating, made use of the sphygmomanometer in the operating theater, and helped advance anesthetic techniques.^[27,28] Cushing also studied the pituitary gland—specifically, basophilic adenomas associated with Cushing disease, as well as the effects of hyperadrenalism.^[25]

Above all, owing to his numerous discoveries, exemplary teaching skills, and wide reach, Cushing is remembered as the founder of neurosurgery.

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