History of neuroscience: John Hughlings Jackson

In 1860, when John Hughlings Jackson was just beginning his career as a physician, neurology did not yet exist as a medical specialty. In fact, at that time there had been little attention paid to developing a standard approach to treating patients with neurological disease. Such an approach was one of Jackson's greatest contributions to neuroscience. He advocated for examining each patient individually in an attempt to identify the biological underpinnings of neurological disorders. This examination, Jackson asserted, should be guided by the tenets of localization of function, which had been popularized by Franz Joseph Gall in the decades before Jackson was born. Concordant with these tenets, Jackson believed that neurological dysfunction could be traced back to dysfunction in specific foci of the nervous system, and the ability to identify the part of the nervous system that was affected to produce a disease was critical for making an accurate diagnosis.

Jackson's perspective on understanding neurological diseases is exemplified by his efforts to elucidate the neurobiological origins of epilepsy---the work he is probably best known for. Jackson's observations on epilepsy date back to the very beginning of his medical career. At that time, the most popular explanation for epileptic seizures was that they were associated with abnormal function in a region of the brain known as the corpus striatum, a term that refers to a composite structure consisting of the striatum and the globus pallidus. The corpus striatum was known to be involved with motor functions, which caused it to be implicated in epileptic seizures as well.

Jackson, however, began to suspect that the cerebral cortex participated in creating the convulsions that epileptics suffered from during seizures. To support this hypothesis, he cited cases where patients experienced convulsions that primarily struck one side of the body. Very often, Jackson argued, these patients upon autopsy would display damage to the cerebral hemisphere on the opposite side of the body that was affected by seizures.

Watch this 2-Minute Neuroscience video to learn more about epilepsy.

Jackson approached the idea that there were certain areas of the cortex devoted to movement with hesitancy for multiple reasons. First, at the time the prevailing view was still that the cortex was unexcitable, and thus would be unlikely to be affected by what Jackson considered to be a disease of increased excitability. Additionally, it was still common in Jackson's time to consider the cortex to be homogenous. Although the concept of localization of function was challenging this idea, many still held the belief that all gray matter in the cortex was equivalent and there were no areas of functional specialization. According to this view, the entire mass of the cortex had to act together to produce some sort of response. Jackson's idea that seizures could be linked to increased excitability in one half of the cortex did not conform to this perspective.

In addition to his observations about the link between hemispheric damage and seizures on the other side of the body, Jackson also noted a unique feature of some of the seizures he observed. He pointed out that in certain patients convulsions started in one specific area of the body and then proceeded to travel outward from that area in a predictable fashion. For example, convulsions might begin in the hand and then move up the arm to the face, and then down the same leg on the same side of the body. Or they might start in the foot and travel up the leg, then down the arm and into the hand on the same side of the body.

This process, later called the Jacksonian march, would help Jackson to formulate some of his most important ideas about the brain. He hypothesized that there were areas of the cortex that were devoted to controlling the movement of different parts of the body. When excitation spreads throughout the cortex, Jackson posited, it stimulates these different areas one by one, creating the Jacksonian march of convulsions through the patient's body. Furthermore, Jackson suggested that the parts of the body that were capable of the most diverse movements (e.g. hand, face, foot) likely had the most space in the cortex devoted to them.

With his observations on epilepsy Jackson was essentially predicting the existence of the motor cortex as well as anticipating the functional arrangement of the gray matter that the motor cortex is made up of. His hypothesis that there was a distinct region of the cerebral cortex devoted to motor function was confirmed in 1870 when Gustav Fritsch and Eduard Hitzig provided experimental evidence of a motor cortex in dogs. The arrangement Jackson envisioned, where one part of the cortex is devoted to one part of the body, we now call somatotopic arrangement. It has been verified by a series of experiments, capped by Wilder Penfield's electrical stimulation studies of the 1930s. It is now common neuroscience knowledge that there are regions of the motor cortex that seem to be devoted specifically to movement of the hands, other regions devoted to the movement of the face, and so on. As Jackson predicted, areas of the body that are involved in more diverse movements generally have more cortical area devoted to them.

Jackson's clinical observations of epilepsy and his hypotheses about the motor regions in the cortex accurately predicted what would soon be discovered through experimentation, and acted as a guide for researchers like Fritsch and Hitzig. Thus, Jackson's work contributed significantly to a better understanding of the organization of the cortex, a region that we now consider to be functionally diverse and intricately arranged---a far cry from the idea of cortical homogeneity common in Jackson's time. Additionally, Jackson's development of a more formalized methodology of observation in neurology has caused him to be considered one of the founding fathers of the field.

Jackson's contributions to neuroscience, however, were much more extensive than there is room to cover here. He wrote copiously on diverse topics ranging from the evolution of the nervous system to aphasia. At a time when our understanding of the brain was still so lacking in comparison to today, Jackson had a brilliant mind that seemed capable of comprehending brain function in a way that has rarely been replicated in the history of neuroscience.

Finger, S. Origins of Neuroscience. New York, NY: Oxford University Press; 1994.

York GK, Steinberg DA (2007). An Introduction to the Life and Work of John Hughlings Jackson. Med Hist Suppl. (26), 3-34

History of neuroscience: Fritsch and Hitzig and the motor cortex

The motor cortex (in red)

The motor cortex (in red)

Neuroscience now views the cerebral cortex as a region of the brain that is essential for sensation, movement, and the heightened level of cognition we associate with humans as compared other animals. In the 1700s, however, many scientists considered the cortex to be a functionally insignificant outer shell of the brain. This corresponds to its original meaning when translated from Latin, which is "bark" (as in tree bark).

By the 1800s, however, neuroscientists had begun to assign functions to the cerebral cortex. Paul Broca, a French physician, published a case study in 1861 that suggested damage to the left frontal lobe (an area later renamed Broca's area) could severely impact language. Around the same time, the British neurologist John Hughlings Jackson was becoming interested in the cortex as an important center for the initiation of movement.

Jackson was studying epileptic seizures, and was intrigued by the fact that partial seizures seemed to start in the hands and then move systematically up the body towards the face. This progression, eventually referred to as a "Jacksonian march", caused Jackson to hypothesize that different areas in the cortex might be responsible for movement in different parts of the body. His belief was that abnormal electrical activity in a partial seizure might be moving through the cortex and at the same time causing abnormal movement to move through the body in a corresponding fashion.

In 1870 two physicians, Gustav Theodor Fritsch and Eduard Hitzig, provided experimental support for Jackson's hypothesized motor area in the cortex. In a morbid experiment that was typical of the day, they restrained live dogs and--without anesthesia--cut away the dogs' skulls to expose an area of cortex. Then, they stimulated that cortex with current from a battery.

Fritsch and Hitzig saw that stimulation of the cortex caused movement of the dogs' contralateral muscles. Furthermore, they found that the stimulation produced movement in a predictable way, as if certain areas of the body were mapped onto the cortex (in the way Jackson had predicted). Thus, Fritsch and Hitzig provided the first widely recognized piece of experimental evidence for what would eventually be known as the motor cortex.

Fritsch and Hitzig went on to support their findings by damaging areas of the cortex in dogs and observing that the dogs then had difficulty with movement in the opposite side of the body. Their original experiments would later be replicated by David Ferrier, but many would remain skeptical of the existence of a motor cortex until the region was mapped in the late 1800s and early 1900s. Now, the motor cortex is recognized as a crucial region in muscle movement, although the details of its involvement (e.g. does it manage complex movement or just muscle stimulation?) are still being worked out.

Gross, C. (2007). The Discovery of Motor Cortex and its Background Journal of the History of the Neurosciences, 16 (3), 320-331 DOI: 10.1080/09647040600630160