Brain structure and function
Goals
- Provide a brief historical overview of brain structure-function relationships.
- Discuss different conceptualization of brain structure-function relationships:
- localization of function
- equipotentiality
- connectionism
Topic Slide
Readings
This material is not covered in PN6. I recommend the following sources for interested students:
Finger, Stanley. Origins of Neuroscience: A History of Explorations Into Brain Function. Oxford University Press, 2001.
Finger, Stanley. Minds behind the Brain: A History of the Pioneers and Their Discoveries. Oxford University Press, 2000.
Gross, Charles G. Brain, Vision, Memory: Tales in the History of Neuroscience. MIT Press, 1998.
There are numerous sites online with historical information about neuroscience:
The Society for Neuroscience hosts a history of neuroscience website.
The Federation of European Neuroscience Societies hosts a history of European neuroscience website with numerous links.
Historical perspectives on brain organization
I sometimes wonder why the study of the relationship between brain structure and psychological function is not more advanced. While much is known about the biology of individual neurons, much less is known about the larger organization that applies to circuits of neurons.
One of the ways to understand structure-function relationships is to study the functional consequences of brain damage. The first writings on this relationship can be found in the Edwin Smith papyrus, which is a 1700 BC copy of a 3000 BC manuscript written by Egyptian battle surgeons. This document describes cases of paralysis and loss of language following brain injuries endured in battle. These functional deficits are described quite matter of factly, there is no allusions to superstition or magic or souls.
Given the ubiquity of warfare, one would have thought that the study of the functional consequences of brain injuries would have advanced greatly in the 5000 years since this papyrus was written. However, the Greeks argued this point. Hippocrates (~460 BC) advocated for the brain as the location of sensation and movement, while Aristotle (~384 BC) strongly and influentially argued for the heart. Galen later claimed that he 'blushed' when he read Aristotle.
As we now know, Galen's views that the ventricles were the site in the brain for sensation, perception, and memory held sway for ~1500 years. Part of the reason for this lack of progress may be related to moral strictures against vivisection. These strictures were loosened in the late 1500s and 1600s, the time of Vesalius the anatomist, and Rembrandt the painter.
Gall vs. Flourens
Franz Joseph Gall (1758-1828) was a anatomist who strongly advocated that function was represented in the brain and, moreover, that different functions were represented in particular parts of the brain. Gall argued that the 'faculties' (functions) are independent, therefore the brain structures representing those functions should be independent. Gall, thus, strongly advocated for Localization of Function in the brain.
Gall noted that individuals differed in the strength of particular faculties and concluded that the brain regions that subserve those faculties should differ in size. This is not unreasonable. However, Gall though that these differences in sizes of brain regions should be evident as bumps in the skull. While it is true that the overall growth of the brain should affect the size of the skull, looking for small regional differences in skull shapes was not reasonable. Based upon this expectation, Gall and (especially his proponents) created the pseudoscience of phrenology. You are probably familiar with the phrenologist's busts, in which the surface of the skull is demarcated into small regions reflecting particular functions.
While Gall's thinking was reasonable and even modern, the phrenological method was not scientific and depended entirely upon correlations and extreme examples. One person who was not amused by phrenology was Napoleon Bonaparte, who was ridiculed in publications of his day showing phrenological readings over drawings of his head. Bonaparte instructed the French Academy of Science to reject Gall's application to join, and appointed Pierre Flourens to investigate Gall's claims.
Flourens had a different perspective than Gall. Flourens believed that understanding is a unit, therefore the organ of understanding should act in a unitary fashion. Flourens also had religious and philosophical objections to localization of function, associating it with determinism, and arguing against its implication for the divisibility of the soul. Flourens was a scientist who studied the effects of experimental brain damage (experimental surgical lesions of the brain) and had concluded in his studies of pigeons that all of cortex participated in higher function. Flourens thus advocated for the equipotentiality of the brain for function.
Evidence for and against the localization of function
Although phrenology was eventually rejected as a pseudoscience, there were other sources of data supporting the concept of localization of function.
- Phineas Gage survived a traumatic injury to the anterior frontal lobe in 1848. This brain injury was the apparent cause of a profound change in his personality.
- Paul Broca's patient 'Tan' suffered (probably by stroke) a lesion to the left lateral frontal lobe that caused him to be unable to speak (1861).
- Fritsch and Hitzig (1870), and then David Ferrier (1873), electrically stimulated the exposed brains of animals and localized discrete sensory and motor regions. Ferrier also made experimental lesions, or ablations, in animals, including monkeys, and demonstrated specific sensory and motor deficits. (Ferrier was charged under anti-vivisection laws).
- Wilder Penfield (1891-1976) electrically stimulated the exposed cortex of human patients undergoing neurosurgery, and mapped sensory and motor regions of the brain (the homunculus) and other brain regions involved in language and memory. His methods are still used today to limit damage to these regions from inadvertent damage during neurosurgical procedures.
- I provided a modern example of electrical brain stimulation from a study I performed with Itzhak Fried here at Yale that elucidated the localization of particular movements and sensations along the medial aspect of the frontal lobes (the so-called, supplementary motor area, or SMA).
- I emphasized that brain stimulation can evoke movements, sensations, etc. However, I also noted that brain stimulation can also disrupt movements, sensations, etc. In the latter case, we would not know what functional effect brain stimulation was having at a particular location unless you asked the patient to perform the function, and the patient was unable to do so.
A digression about electrical stimulation:
Prior to the invention of the Leyden Jar (an early capacitor or battery) in 1745, scientists experience with electricity was restricted to electric fish, lightening, and static electricity. However, once electricity could be stored, it became possible to conduct the types of experiments performed by Fritsch and Hitzig and by Ferrier.
But why would these scientists think that electricity would stimulate brain tissue? Prior work by Galvani in 1791 established the existence of bioelectric forces in living tissue. Giovanni Aldini (Galvani's nephew) carried our ghoulish experiments in which he used electricity to stimulate the movements of muscles in deceased criminals. Aldini's experiments (which he performed as public displays) were thought to be the inspiration for Mary Shelly's novel, Frankenstein: A modern Prometheus.
Although there was a growing consensus that some sensory and motor functions were represented in discrete brain regions, there was contradictory data – particularly with respect to higher functions (i.e., functions beyond sensory reception and direct motor control).
Karl Lashley (1890-1958) was a highly influential American psychologist who attempted to locate memory for maze learning in the rat. He made successive experimental brain lesions of greater size, and concluded that the loss of function was related to the size of the lesion, not the location of the lesion. Lashley's work was interpreted in support of two concepts:
- Cerebral equipotentiality – the ability of any area of cortex to execute the functions of another area. Since Lashley accepted the localization of sensory and motor function, he modified his concept to 'Areal' equipotentiality, or the idea that equipotentiality exists within large subdivisions of cortex.
- Mass Action – that complex patterns of action requires the participation of the whole of cortex.
For those interested in a more comprehensive history of the concepts of localization of function and equipotentiality, this paper by Tizzard provides an interesting review.
Connections, disconnexion, and connectionism
In lecture 1, I discussed the implications of having more neurons upon connections in the brain. If there are 'N' neurons in the brain, and all were connected to each other, we would have N*(N-1) total connections. The sheer weight and volume of the connections would be too great, and so evolution would likely select for efficient connectivity patterns.
Sparse connections and modularity
One connectivity pattern favoring localized function would have the neurons within small regions highly interconnected since the connections could be short and the axons thin. More distant connections would be relatively sparse. This pattern could form the substrate for modular brain processing, in which a relatively small number of dedicated modules exist within the brain to carry out highly specific functions (e.g., face processing). These modules would require dense intra-connections to compute their outcomes. However, they were require sparse inter-connections to output their results to other modules.
The speed of transmission within an axon is dependent upon its diameter and whether or not it is myelinated. We will consider these two facts in more detail in upcoming lectures. Suffice it for now to say that long distance connections required larger axons with myelin sheaths, and thus are much larger than local axons.
Disconnexion syndromes
Some scientists have emphasized the connections between modular brain regions in their models of brain functions. American neurologist Norman Geschwind explained certain symptoms that occurred in patients with stroke-related language comprehension and speech deficits as disconnexions between different language centers in the brain.
Connectionism
Connectionism refers to the idea that a large number of simple but highly interconnected units engage in parallel processing through which the strengths of connections between units, or networks of units, represent mental states as emergent properties. Connectionism is strongly associated with the computational approach of neural networks.
I include connectionism here partially for completeness, and partially because the simple units specified and the learning nature of neural networks provides a possible substrate for equipotentiality, while not being contradicted by the occurrence of localized function.
Connectionism was very popular in the Cognitive Science of the 1980s in which the units were conceptualized as simple neurons (hence the term, neural networks). Connectionism has had a resurgent of interest in more recent neuroscientific studies of brain function.
Conclusions
The relationship between brain structure and function is more complex than it may appear on the surface. The arguments over localization, modularity, equipotentiality, and connectionism are still present in studies performed today.
It is too early in the course to draw strong conclusions, but here are a few pointers. In general, the evidence for highly localized function is more secure for sensory input and direct motor control than it is for higher functions. However, as we will learn, some brain areas thought to be highly specific for function can show remarkable flexibility following damage or abnormal development. Also, a function can appear at different levels of abstraction and in different locations in the nervous system. Think, for example, about writing your name. You can easily imagine that the instructions for writing your name is stored as a sequence of motor commands for your hand. But you can also write your name holding a pen in your mouth, or with your foot. Even the lowly (but essential for survival) function of vomiting is controlled locally in the enteric nervous system, but also in the medulla central nervous system.
Prerecorded lectures for Fall, 2020
Bioelectricity (15:30)
Structure – Function (37:47)
