History of neuroscience

From the ancient Egyptian mummifications to 18th-century scientific research on "globules" and neurons, there is evidence of neuroscience practice throughout the early periods of history. The early civilizations lacked adequate means to obtain knowledge about the human brain. Their assumptions about the inner workings of the mind, therefore, were not accurate. Early views on the function of the brain regarded it to be a form of "cranial stuffing" of sorts. In ancient Egypt, from the late Middle Kingdom onwards, in preparation for mummification, the brain was regularly removed, for it was the heart that was assumed to be the seat of intelligence. According to Herodotus, during the first step of mummification: "The most perfect practice is to extract as much of the brain as possible with an iron hook, and what the hook cannot reach is mixed with drugs." Over the next five thousand years, this view came to be reversed; the brain is now known to be the seat of intelligence, although colloquial variations of the former remain as in "memorizing something by heart".

Antiquity

The earliest reference to the brain occurs in the Edwin Smith Surgical Papyrus, written in the 17th century BC. The hieroglyph for brain, occurring eight times in this papyrus, describes the symptoms, diagnosis, and prognosis of two patients, wounded in the head, who had compound fractures of the skull. The assessments of the author (a battlefield surgeon) of the papyrus allude to ancient Egyptians having a vague recognition of the effects of head trauma. While the symptoms are well written and detailed, the absence of a medical precedent is apparent. The author of the passage notes "the pulsations of the exposed brain" and compared the surface of the brain to the rippling surface of copper slag (which indeed has a gyral-sulcal pattern). The laterality of injury was related to the laterality of symptom, and both aphasia ("he speaks not to thee") and seizures ("he shudders exceedingly") after head injury were described. Observations by ancient civilizations of the human brain suggest only a relative understanding of the basic mechanics and the importance of cranial security. Furthermore, considering the general consensus of medical practice pertaining to human anatomy was based on myths and superstition, the thoughts of the battlefield surgeon appear to be empirical and based on logical deduction and simple observation.

In Ancient Greece, interest in the brain began with the work of Alcmaeon, who appeared to have dissected the eye and related the brain to vision. He also suggested that the brain, not the heart, was the organ that ruled the body (what Stoics would call the ''hegemonikon'') and that the senses were dependent on the brain. According to ancient authorities, Alcmaeon believed the power of the brain to synthesize sensations made it also the seat of memories and thought. The author of ''On the Sacred Disease'', part of the Hippocratic corpus, likewise believed the brain to be the seat of intelligence.

The debate regarding the ''hegemonikon'' persisted among ancient Greek philosophers and physicians for a very long time. Already in the 4th century BC, Aristotle thought that the heart was the seat of intelligence, while the brain was a cooling mechanism for the blood. He reasoned that humans are more rational than the beasts because, among other reasons, they have a larger brain to cool their hot-bloodedness. On the opposite end, during the Hellenistic period, Herophilus and Erasistratus of Alexandria engaged in studies that involved dissecting human bodies, providing evidence for the primacy of the brain. They affirmed the distinction between the cerebrum and the cerebellum, and identifying the ventricles and the ''dura mater''. Their works are now mostly lost, and we know about their achievements due mostly to secondary sources. Some of their discoveries had to be re-discovered a millennium after their death.

During the Roman Empire, the Greek physician and philosopher Galen dissected the brains of oxen, Barbary apes, swine, and other non-human mammals. He concluded that, as the cerebellum was denser than the brain, it must control the muscles, while as the cerebrum was soft, it must be where the senses were processed. Galen further theorized that the brain functioned by the movement of animal spirits through the ventricles. He also noted that specific spinal nerves controlled specific muscles, and had the idea of the reciprocal action of muscles. Only in the 19th century, in the work of François Magendie and Charles Bell, would the understanding of spinal function surpass that of Galen.

Medieval to Early Modern

Islamic medicine in the middle ages was focused on how the mind and body interacted and emphasized a need to understand mental health.
Circa 1000, Al-Zahrawi, living in Islamic Iberia, evaluated neurological patients and performed surgical treatments of head injuries, skull fractures, spinal injuries, hydrocephalus, subdural effusions and headache. In Persia, Avicenna (Ibn-Sina) presented detailed knowledge about skull fractures and their surgical treatments.
Avicenna is regarded by some as the father of modern medicine. He wrote 40 pieces on medicine with the most notable being the Qanun, a medical encyclopedia that would become a staple at universities for nearly a hundred years. He also explained phenomena such as, insomnia, mania, hallucinations, nightmares, dementia, epilepsy, stroke, paralysis, vertigo, melancholia and tremors. He also discovered a condition similar to schizophrenia, which he called Junun Mufrit, characterized by agitation, behavioral and sleep disturbances, giving inappropriate answers to questions, and occasional inability to speak. Avicenna also discovered the cerebellar vermis, which he simply called the vermis, and the caudate nucleus. Both terms are still used in neuroanatomy today. He was also the first person to associate mental deficits with deficits in the brain's middle ventricle or frontal lobe. Abulcasis, Averroes, Avenzoar, and Maimonides, active in the Medieval Muslim world, also described a number of medical problems related to the brain.

Between the 13th and 14th centuries, the first anatomy textbooks in Europe, which included a description of the brain, were written by Mondino de Luzzi and Guido da Vigevano.

Renaissance

Work by Andreas Vesalius on human cadavers found problems with the Galenic view of anatomy. Vesalius noted many structural characteristics of both the brain and general nervous system during his dissections. In addition to recording many anatomical features such as the putamen and corpus callosum, Vesalius proposed that the brain was made up of seven pairs of 'brain nerves', each with a specialized function. Other scholars furthered Vesalius' work by adding their own detailed sketches of the human brain.

Scientific Revolution

In the 17th century, René Descartes studied the physiology of the brain, proposing the theory of dualism to tackle the issue of the brain's relation to the mind. He suggested that the pineal gland was where the mind interacted with the body after recording the brain mechanisms responsible for circulating cerebrospinal fluid. Jan Swammerdam placed severed frog thigh muscle in an airtight syringe with a small amount of water in the tip and when he caused the muscle to contract by irritating the nerve, the water level did not rise but rather was lowered by a minute amount debunking balloonist theory. The idea that nerve stimulation led to movement had important implications by putting forward the idea that behaviour is based on stimuli. Thomas Willis studied the brain, nerves, and behavior to develop neurologic treatments. He described in great detail the structure of the brainstem, the cerebellum, the ventricles, and the cerebral hemispheres.

Modern Period

The role of electricity in nerves was first observed in dissected frogs by Luigi Galvani, Lucia Galeazzi Galvani and Giovanni Aldini in the second half of the 18th century. In 1811, César Julien Jean Legallois defined a specific function of a brain region for the first time. He studied respiration in animal dissection and lesions, and found the center of respiration in the medulla oblongata. Between 1811 and 1824, Charles Bell and François Magendie discovered through dissection and vivisection that the ventral roots in spine transmit motor impulses and the posterior roots receive sensory input ( Bell-Magendie law). In the 1820s, Jean Pierre Flourens pioneered the experimental method of carrying out localized lesions of the brain in animals describing their effects on motricity, sensibility and behavior. He concluded that the ablation of the cerebellum resulted in movements that “were not regular and coordinated". At mid century, Emil du Bois-Reymond, Johannes Peter Müller, and Hermann von Helmholtz showed neurons were electrically excitable and that their activity predictably affected the electrical state of adjacent neurons.

In 1848, John Martyn Harlow described that Phineas Gage had his frontal lobe pierced by an iron tamping rod in a blasting accident. He became a case study in the connection between the prefrontal cortex and executive functions. In 1861, Paul Broca heard of a patient at the Bicêtre Hospital who had a 21-year progressive loss of speech and paralysis but neither a loss of comprehension nor mental function. Broca performed an autopsy and determined that the patient had a lesion in the frontal lobe in the left cerebral hemisphere. Broca published his findings from the autopsies of twelve patients in 1865. His work inspired others to perform careful autopsies with the aim of linking more brain regions to sensory and motor functions. Another French neurologist, Marc Dax, made similar observations a generation earlier.Principles of Neural Science, 4th ed. Eric R. Kandel, James H. Schwartz, Thomas M. Jessel, eds. McGraw-Hill: New York, NY. 2000. Broca's hypothesis was supported by Gustav Fritsch and Eduard Hitzig who discovered in 1870 that electrical stimulation of motor cortex caused involuntary muscular contractions of specific parts of a dog's body and by observations of epileptic patients conducted by John Hughlings Jackson, who correctly deduced in the 1870s the organization of the motor cortex by watching the progression of seizures through the body. Carl Wernicke further developed the theory of the specialization of specific brain structures in language comprehension and production. Richard Caton presented his findings in 1875 about electrical phenomena of the cerebral hemispheres of rabbits and monkeys. In 1878, Hermann Munk found in dogs and monkeys that vision was localized in the occipital cortical area, David Ferrier found in 1881 that audition was localized in the superior temporal gyrus and Harvey Cushing found in 1909 that the sense of touch was localized in the postcentral gyrus. Modern research still uses the Korbinian Brodmann's cytoarchitectonic (referring to study of cell structure) anatomical definitions from this era in continuing to show that distinct areas of the cortex are activated in the execution of specific tasks.

Studies of the brain became more sophisticated after the invention of the microscope and the development of a staining procedure by Camillo Golgi during the late 1890s that used a silver chromate salt to reveal the intricate structures of single neurons. His technique was used by Santiago Ramón y Cajal and led to the formation of the neuron doctrine, the hypothesis that the functional unit of the brain is the neuron. Golgi and Ramón y Cajal shared the Nobel Prize in Physiology or Medicine in 1906 for their extensive observations, descriptions and categorizations of neurons throughout the brain. The hypotheses of the neuron doctrine were supported by experiments following Galvani's pioneering work in the electrical excitability of muscles and neurons. In 1898, British scientist John Newport Langley first coined the term "autonomic" in classifying the connections of nerve fibers to peripheral nerve cells. Langley is known as one of the fathers of the chemical receptor theory, and as the origin of the concept of "receptive substance". Towards the end of the nineteenth century Francis Gotch conducted several experiments on nervous system function. In 1899 he described the "inexcitable" or "refractory phase" that takes place between nerve impulses. His primary focus was on how nerve interaction affected the muscles and eyes.

Heinrich Obersteiner in 1887 founded the ‘‘Institute for Anatomy and Physiology of the CNS’’, later called Neurological or Obersteiner Institute of the Vienna University School of Medicine. It was one of the first brain research institutions in the world. He studied the cerebellar cortex, described the Redlich–Obersteiner's zone

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