History of neuroscience: Luigi Galvani

Luigi galvani (1737-1798)

By the start of the 18th century, brain scientists were beginning to develop a better understanding of the complex anatomy of the nervous system. The physiology of the brain, however---or the way in which the brain functions---was still an area dominated by speculation and lacking in experimental evidence. One extremely important but unanswered question at the time involved the physiology of the nerves. Scientists in the beginning of the 18th century still relied on observations made by the ancient Greeks when attempting to explain nerve function, but those insights did not seem to be matching up with recent laboratory discoveries.

The dominant hypothesis regarding nerve function at the beginning of the 1700s centered around the ambiguous concept of animal spirits. The notion of animal spirits is thought to have originated with the ancient Greeks, and was advocated by Galen---whose influence may have helped the doctrine remain dominant for over 1500 years.

The animal spirits hypothesis suggested that the hollow nerves of the body were filled with spirits---invisible, intangible substances that acted in a mysterious manner to cause movement or allow sensation to occur. According to Galen's view, a form of spirits called natural spirits were produced in the liver after the consumption of food. Natural spirits then were sent to the heart, where they were converted to vital spirits. Vital spirits were carried in the carotid arteries to the brain to either the ventricles or to a complex of arteries at the base of the brain that Galen called the rete mirabile, or "wonderful net." In one of these locations, the vital spirits were converted to animal spirits---the highest form of spirits. The animal spirits were then stored in the ventricles until they were needed.

Although the animal spirits hypothesis was still the prevailing hypothesis at the start of the 18th century, investigators were not having success in experimentally verifying the existence of the spirits. This led to the exploration of other hypotheses, like Thomas Willis' idea that the nerves carried fluid that dripped onto muscles to stimulate them. These new hypotheses, however, also did not seem to stand up to experimental scrutiny. But this changed early in the 18th century when some scientists began to suggest that electricity was the enigmatic substance that filled the nerves.

At the time, appreciation for the wonders of electricity was rapidly growing. The first devices that could produce and store electricity, known respectively as friction machines and Leyden jars, appeared in the first half of the 18th century. These contraptions could be used to create dazzling displays, and became a popular novelty at social engagements. It was also soon recognized, however, that electricity had some potential medical applications. It seemed to be particularly effective at stimulating the muscles of paralyzed limbs to contract.

This led some to hypothesize that electricity was the substance that flowed through the nerves. This hypothesis was bolstered when it was verified that the shocks produced by electric fish (e.g. the electric ray) were caused by actual electricity, as it proved that electricity could exist within the confines of an animal's nervous system. It was at this time, when excitement about electricity as a mechanistic component of the nervous system was beginning to grow, that Luigi Galvani would make his seminal contributions to the field.

Galvani was a doctor and professor of anatomy at the University of Bologna in Italy. In the 1770s, he began to explore electricity and its association with the nerves, conducting his experiments in his own home and mostly with frogs as the subjects.

An illustration from Galvani's 1791 publication that shows some of the devices (along with frog preparations) used in his experiments.

In 1791, after 10 years of research into the subject, Galvani published the work that would make him famous, his Commentary on the Effects of Electricity on Muscular Motion. In the treatise, Galvani described a series of experiments that made a strong case for the natural involvement of electricity in the nervous system. First, Galvani discussed an observation that occurred serendipitously. He had placed a dissected frog on a table next to an electrical machine, and when one of his assistants touched the frog's nerves with a metal scalpel at the same time as the electrical machine emitted a spark, the frog's leg muscle contracted, causing a convulsive movement of the limb. 

Galvani further explored the ability of electricity to cause muscle contractions. He found that when a wire was stretched from the electrical machine to the frog's leg, a convulsion was also elicited. He extended the finding to mammals, observing that similar types of contractions could be generated in chickens and sheep.

Galvani then began to investigate the effects of natural sources of electricity, showing that lightning (as conducted by a lightning rod and down a wire) was also capable of producing muscle contractions when it was given a path to a frog's limbs. These experiments were all interesting, but they were not groundbreaking on their own. Other investigators had observed the ability of electricity to elicit muscle movement. But the next experiments Galvani conducted, and the resultant deductions he made, are what really caused his research to stand apart from the rest.

As a way to attach conductors or hang the frogs outside his home for experiments with lightning, Galvani had fastened brass hooks to the frogs' spinal cords. He was inside with a frog that had a brass hook attached to it when he pressed the frog, along with the hook, up against a metal plate. To Galvani's surprise, the frog exhibited the same type of convulsive movements the application of electricity had caused. This suggested the movements were not dependent on some external source of electricity, and led Galvani to make the deduction that "the electricity was inherent in the animal itself."

Galvani went on to hypothesize that this "animal electricity" was produced by the brain and distributed by the nerves to the muscles (the brain as the "source" of electricity would not stand up to scrutiny once researchers began to better understand the electrical properties of neurons). He also postulated that the nerves must be covered with a fatty insulatory material---a hypothesis that preceded the discovery of that insulatory material (i.e. myelin) by over 60 years.

Galvani's findings and deductions were very influential. Other hypotheses about nerve function, like the animal spirits doctrine, began to fall out of favor. Although many questions about the electrical properties of the nervous system remained, at least now investigators had a mechanism for nerve function that could be observed and measured (unlike the elusive animal spirits). Galvani's discoveries would form the foundation of the modern study of nerve function.

Galvani was not able to fully appreciate the significance of his observations or the popularity they engendered. His wife died in the same year he published his findings (1791). He was devastated and never seemed to be the same emotionally. He spent the next seven years defending his conclusions from critics, especially the well-known well-known Alessandro Volta, who incessantly attacked Galvani's work as insufficient to support the deductions he made. Galvani died in 1798, uncertain of how important his discoveries would become and unaware that they would be an essential piece in the foundation modern neuroscience has been built upon.

Finger S. Minds Behind the Brain. New York, NY: Oxford University Press; 2000.

Galvani L. Commentary of the effects of electricity on muscular motion. Foley MG, translator. Norwalk, CT: Burndy Library; 1953.

Know your brain: Broca's area

broca's area highlighted in red.

Where is Broca's area?

Although the anatomical definitions of Broca's area are not completely consistent, it is generally considered to make up some part of a region called the inferior frontal gyrus, which is found in the frontal lobe. Some researchers ascribe Broca's area to the entire inferior frontal gyrus, while others consider it to only make up a portion of the inferior frontal gyrus. Still others consider the boundary of Broca's area to expand slightly outside of the inferior frontal gyrus.

In the vast majority of individuals, Broca's area is considered to reside in the left cerebral hemisphere. This is due to the role of Broca's area in language and the typical left hemisphere dominance of language function; there is, however, a corresponding region in the right hemisphere---it is just not thought to play as significant a role in language production.

What is Broca's area and what does it do?

In April of 1861, a 51-year old man named Louis Victor Leborgne was admitted to the surgical unit of young physician named Paul Pierre Broca. Leborgne had a severe leg infection that had become gangrenous, and Broca did not think it likely he would survive. Broca took much more interest in Leborgne than he would have in just another patient with cellulitis, however, as Leborgne also had a more unique disorder. The disorder, which Broca would come to all aphemia and which would later be named aphasia (aphasia is the name that would stick), caused Leborgne to have an extremely difficult time producing language. In fact the only word he could consistently generate was the word "tan," which he would often utter in two-word refrains of "tan, tan." Leborgne had thoughts he wanted to communicate, but he was unable to. He used gestures to interact with Broca, but sometimes became frustrated at his inability to express himself---causing him to utter the only other words Broca reported hearing him say: "sacre nom de Dieu," or God damn.

Broca saw an opportunity in Leborgne. At the time there was a debate occurring in some circles of the scientific community; it was centered around the question of whether certain areas of the brain were specialized for certain functions, or if the entire brain was utilized in the performance of every function. The former view, sometimes referred to as localization of function, was the perspective Broca was leaning toward.

One function that advocates of localization (sometimes called localizationists) had argued strongly in favor of being localized was speech. Previous evidence had suggested that the faculty for speech might be centered in the frontal lobes. Thus, when Broca encountered Leborgne he saw an opportunity to test this hypothesis. After Leborgne died, Broca quickly performed an autopsy. Upon examining the brain, Broca found a crater in the left frontal lobe that he described as being as large as a "chicken's egg." 

The combination of a left frontal lobe lesion with a deficit in the production of speech caused Broca to recognize this case as a seminal one in the localization argument. He presented the case before groups of intrigued scientists in Paris, and for some it was the evidence that swayed them to favor a more localizationist approach to the brain. Broca was considered a respectable and cautious scientist---not one who jumped to conclusions without an adequate amount of evidence. Thus, the fact that he had come to believe that speech might be localized to the frontal lobes was influential.

Not being completely convinced by only one case, however, Broca continued to look for other cases involving frontal lobe damage and speech deficits after Leborgne. Within just a couple of years, he had identified eight cases. What was perhaps most shocking to Broca was that---in every case---the damage was not only in a similar location in the frontal lobe, but it was also always on the left side. The idea that the two cerebral hemispheres were different in some way was relatively unheard of at this point in time, but the clinical evidence would soon have Broca arguing for that hypothesis along with the localization of speech.

The region Broca had discovered would first be known as Broca's convolution, then Broca's centre, and then---by the early 1900s---Broca's area. In addition to becoming recognized as an important part of the brain for language production, Broca's area would be a critical piece of evidence in the debate over localization of function. Although it would not on its own end the localization debate, it helped to convince many that at least some functions are assigned to relatively circumscribed areas of the brain.

Leborgne's condition became known as Broca's aphasia (also known as expressive aphasia). Its main symptom is a deficit in the ability to produce language (often any type of language, including both spoken and written). Thus, the primary function most often attributed to Broca's area inolves language production. Not long after Broca, however, investigators realized that a behavior as complex as speech is not likely to involve only one small region of the brain. Thus, it is now believed that Broca's area plays an important role in language production through communication with several other brain regions.

The precise role of Broca's area in language production is still debated. In other words, evidence suggests that damage to Broca's area can disrupt language production, but nobody is quite sure exactly what specific language-related function is lost to cause that disruption. Some have asserted Broca's area is involved with producing motor movements that allow speech to be produced. Others have argued that it is involved with verbal working memory, syntax, grammar, or all of the above.  

Broca's area is thought to also have a variety of other linguistic and non-linguistic functions. In addition to language production, it is now recognized that Broca's area plays an important role in language comprehension. Broca's area is also believed to be involved in movement and action, and has been found to be active during planning movement, imitating movement, and understanding another's movement. Additionally, it has been hypothesized that Broca's area contains mirror neurons that are activated during hand and lip movements and when observing others make similar movements.

Although some of these additional functions linked to Broca's area may be associated with the region's role in language, they also make it clear that the function of Broca's area is much more complex than originally thought. Thus, the role of Broca's area in linguistic and non-linguistic functions is still being elucidated, and will likely be modified and expanded upon many times in the future.

Schiller F. 1979. Paul Broca: Founder of French Anthropology, Explorer of the Brain. New York: Oxford University Press.

Read more - History of neuroscience: Paul Broca

2-Minute Neuroscience: Pineal Gland

The pineal gland is a pine cone shaped structure located in the diencephalon whose main function is the secretion of melatonin, a hormone that is best known for its role in regulating circadian rhythms. The pineal gland secretes melatonin throughout the 24-hour cycle, with secretion being highest in the middle of the night and lowest during daylight hours. In this video, I discuss the pineal gland and melatonin secretion, including 24-hour patterns of melatonin secretion and how the pineal gland uses signals from the retina about how much light is in the environment to determine what the time of day is.

Know your brain: Posterior parietal cortex

Where is the posterior parietal cortex?

posterior parietal cortex in blue.

The posterior parietal cortex comprises the region of the parietal cortex that is posterior to the primary somatosensory cortex and its adjacent sulcus, the postcentral sulcus. The posterior parietal cortex itself is divided into an upper and lower portion: the superior parietal lobule and inferior parietal lobule, respectively. These two lobules are separated from one another by a sulcus called the intraparietal sulcus.

What is the posterior parietal cortex and what does it do?

The posterior parietal cortex receives input from a collection of sensory areas as well as a variety of other regions of the brain, and is thought to integrate that input to facilitate the execution of functions that require diverse information. It has been associated with a number of these functions, which are sometimes called "higher-order" functions; it is probably best known, however, for its role in attention.

Through attempts to find the brain regions that facilitate attention, researchers have identified two attention-related networks that involve the posterior parietal cortex; these are termed the dorsal and ventral fronto-parietal systems. The dorsal system is found in both cerebral hemispheres and includes areas of the superior parietal lobule and intraparietal sulcus as well as a region of the frontal cortex that is involved in eye movements and visual perception known as the frontal eye field. The dorsal system is thought to be involved with what is known as "endogenous attention," which involves attention that is directed based on individual goals or desires. For example, if you are attempting to focus your attention to read this article, you are utilizing endogenous attention. 

The ventral system is found primarily in the right cerebral hemisphere and includes the area where the temporal and parietal lobes meet (the temporo-parietal junction), the intraparietal sulcus, and areas of the frontal cortex. The ventral system seems to be involved more in what is termed "exogenous attention," or attention that is directed towards external stimuli that are not being attended to by endogenous attentional processes. For example, if you were reading this article in a library and someone a few tables over shouted, breaking the complete silence of the room, you would suddenly and reflexively direct your attention to the person who shouted. This type of attention is not associated with your own goals or desires, and falls under the rubric of exogenous attention.

an example of what a clock drawn by a patient with hemispatial neglect might look like.

The importance of the posterior parietal cortex to attention is perhaps best exemplified by a condition that can occur after damage to the posterior parietal cortex known as hemispatial or contralateral neglect. Hemispatial neglect is most frequently associated with damage to the posterior parietal cortex in the right cerebral hemisphere (due to stroke, head trauma, etc.), after which the patient ceases to devote attention to the left side of their body and visual field. These patients can act as if they don't perceive anything in a certain part of their visual field; if asked to draw a picture, they will often not include a significant portion (up to half) of the item drawn, they may eat only about half of the food off of a plate, and shave or put makeup on only half of their face. Some patients may even deny that part of their body on the neglected side is theirs in an attempt to reject the idea that they are suffering from a neurological condition.

The posterior parietal cortex is also believed to be involved in some aspects of motor function, such as planning movements and integrating visual information with movement to facilitate actions like reaching and grasping. Additionally, regions of the posterior parietal cortex are thought to contain neurons called mirror neurons, which are activated not only when a particular action is performed but also when someone else is observed performing the same action. The true function of mirror neurons is yet to be determined. Some hypothesize that they are important to allowing us to learn by imitation, or even for understanding the actions of others; but there are also many who are critical of these hypotheses, arguing they are too speculative and lacking evidential support.

Additionally, the posterior parietal cortex is thought to be involved in language as well as the ability to understand numbers and arithmetic. Thus, its functions span a large spectrum ranging from attention to movement to number processing. Research is still being done to better understand the role of the posterior parietal cortex in these actions and others. What is known about the posterior parietal cortex already, however, makes it one of the more intriguing areas in the brain.

Caspers S, Amunts K, Zilles K. Posterior Parietal Cortex: Multimodal Association Cortex. JK Mai and G Paxinos (Eds.). 2012; Elsevier, New York.