By Heidi Reyst, Ph.D., CBIST
Rainbow Rehabilitation Centers

For nearly a century there has been evidence that the brain is far more capable of change than has been given credit. Conventional science has largely ignored this data in favor of the Doctrine of Localization whereby one discrete location of the brain accounts for one specific function, and if injury occurs to that location, that function is thereby lost.

Research has now overwhelmingly shown that our brains are “plastic” meaning our cortex is dynamic and can yield to behavioral experience. For well over a century, however, conventional neuroscience has largely stuck with the principles of the Doctrine of Localization, and notwithstanding a few scientists, has essentially ignored any and all discoveries that fostered the idea that our brains are capable of rewiring, reorganizing and otherwise relearning after injury.

There were numerous opportunities for conventional science to embrace the principles of neuroplasticity, but as the following timeline demonstrates, many of those opportunities were missed or ultimately ignored.

In the late 1700s to early 1800s a debate raged among scientists of the time as to whether brain areas have independent, specific functions (termed localism), or whether the whole brain worked in aggregate to produce function (holism).For the players in this debate, these two concepts were diametrically opposed—the brain either operated in a localized or holistic manner. And, for quite some time, it seemed the newest theory,  experimental evidence, or opportune patient provided the current frontrunner in this tense and deeply passionate intellectual debate.

The Neuroplasticity Timeline

c. 1800

Joseph GallOne of the main proponents of localism was Joseph Gall the founder of phrenology (which he termed organology), along with his student Johann Spurzheim. The basis of  phrenology was that the brain was divided into 27 faculties ranging from pride to the sense of colors, to verbal memory to morality. Gall and Spurzheim thought that by analyzing the form, features and measurements of individuals’ skulls they could estimate the size of different brain areas which they would then use to make assertions about the development of their faculties. Gall, in particular, noted that he observed correlations between psychological tendencies and skull shapes.  Phrenology, while lacking basic scientific rigor, was the first  venture into the idea that one area of the brain was responsible for a specific faculty or in modern terms, function.

c. 1820Marie Jean Pierre Flourens

Many at the time viewed localism as naive, probably due in part to the lack of scientific rigor of phrenology, and so the only alternative to localism was holism. On the holistic side of the debate, was Marie Jean Pierre Flourens. He was appointed by Napoleon Bonaparte to address the lack of rigor and put the issue to rest. So in the 1820s, he began a series of experiments on pigeons and rabbits. In his experiments, he removed different areas of the brain to see how it affected their behavior. He found that removal of the cerebellum resulted in dis-coordination of muscles, removal of the frontal lobe resulted in problems with judgment and perception, and that removal of the medulla resulted in death (www.britannica. com).

As a result of this work, Flourens’ conclusion was that the cerebral hemispheres were “responsible for higher psychic and intellectual capabilities” (, though he recognized that certain functions were located in certain parts of the brain. Moreover, through the removal of large sections of the cerebral lobes, without any resulting loss of function, he concluded that the brain itself acts as a “functional entity” (Yildirim and Sarikcioglu, 2007). Flourens understanding of the brain as a functional entity was that “the cerebral lobes operate in unison for the full exercise of their functions…the cerebral cortex functioned as an indivisible whole” (cited in Pearce, 2009). It was Flourens’ pioneering research that ultimately discounted phrenology and put the ideas of Holism at the forefront of the debate.

1861Pierre Paul BrocaBroca's & Wernicke's Area

It was in 1861, however, that the debate took a persistent turn towards localism. Physician Pierre Paul Broca, through his research, was able to tie speech deficits resulting from brain injuries to specific areas of the brain. In particular, he found that patients with lesions in the left frontal lobe had characteristic impairments of speech output, known today as expressive aphasia. Thus, he demonstrated that once an area responsible for a function was damaged by a lesion, the function was thus lost. Since CT or MRI were not available tools to detect lesions within individuals who were living, Broca and those studying the brain at this time had only autopsy available to determine that a specific area of the brain was in fact damaged (in this case the left inferior frontal lobe, now known as Broca’s area). 


On the heels of Broca’s assertion that “one speaks with the left hemisphere”, Jules Cotard in studying children with significant brain disease that affected the left hemisphere including the frontal lobe area (either congenital or acquired very early on) did not display aphasia as would be expected (Doidge, 2007). His claim was that if at an early age, lesions to Broca’s area did not result in impairment, but did so at later ages, that another area of the brain must then take over function. This was the first time that a neuroscientist speculated that when one area of the brain is injured other areas of the brain may take over for the functions that area previously provided.


German scientists Gustav Fritsch and Eduard Hitzig were the first to provide experimental evidence for cerebral localization, by showing that electrical stimulation of the cortex of un-anaesthetized dogs resulted in movement. More specifically, they found that specific areas of the brain were organized topographically (mapping of the surface area) within the cerebral cortex, and that stimulation of certain cortical areas corresponded to movement of specific body parts. In essence, they were able to identify what is now well understood to be the motor cortex of the frontal lobe.


Thirteen years after Paul Broca found that lesions of the left side of the frontal cortex resulted in speech impairments, Carl Wernicke noted that left-sided temporal lobe lesions resulted in impairments in language comprehension, or the ability to understand language (Doidge, 2007). This, of course, is now known as Wernicke’s area. The mapping of the brain thus became the hallmark of localism.

Norman Doidge (2007) in describing the stronghold of localization at that time noted, “unfortunately, though, the case for localization was soon exaggerated. It went from being a series of intriguing correlations (observations that damage to specific brain areas led to the loss of specific mental functions) to a general theory that declared that every brain function had only one hardwired location—an idea summarized by the phrase ‘one function, one location,’ meaning that if a part was damaged, the brain could not reorganize itself or recover that lost function”.

1876Otto Soltmann

Otto Soltmann took Fritsch’s and Hitzig’s research further, by examining the differences in age-related response to brain damage. Specifically, he started looking at the motor cortex areas in very young puppies and found that stimulation of the motor areas did not induce front paw movements until 10 days of age (Finger, Beyer and Koehler, 2000). He also found that as the animals aged, the part of the motor cortex that controlled the movement grew larger, and then settled to its final size in adulthood.

In subsequent research, Soltmann looked at the motor cortex after injury throughout the age range of dogs (Finger, Beyer and Koehler, 2000). He found that for puppies too young for motor stimulation to result in movement, lesions of the motor areas did not result in noticeable functional problems. Older dogs subjected to the same lesion, however, did experience the anticipated impairments. This was the first experimental evidence that showed other areas of the motor cortex may well have taken over for the damaged area—an idea termed vicariation.

By the time of Soltmann’s work, localism had taken hold, in the strict sense of the definition of the time, in that one area, one function meant permanent loss of function. Henceforth, any work contrary to the ideals of localism was ignored, including that of Otto Soltmann.

c. 1884

John Hughlings-Jackson,  a pioneer of neurology in Britain in the mid to late 1800s, laid the groundwork for future theories on brain organization, much of which is the basis of modern neurology. Hughlings-Jackson, based on his research into seizures, further supported the idea of a somatotopic representation of the brain (i.e., that there is an orderly and specific relation between a particular body part and its representation in the brain). One of the enduring theories laid down by Hughlings-Jackson was that the mind is based on physical representations within the brain and not metaphysical action (i.e., supernatural, godly). York and Steinberg (2011) noted that he believed that:

…the nervous system is a purely physical mechanism. This neurological idea forms the basis of clinical neurophysiology. The ostensibly atheistic principle that the nervous system is  exclusively sensorimotor excludes any reference to metaphysical objects or actions, and forms the basis of modern physiology. It was a brave assertion in Victorian London, in that Darwin’s theory of evolution by natural selection evoked the ire of the Bishop of Oxford (p. 3108).

Hughlings-Jackson also theorized that the human nervous system evolved “with increasingly higher levels of re-representation of basic sensorimotor representations” and that “sensory impressions and representations of bodily movements are embedded in more complex structures and processes” (Franz and Gillette, 2011, p. 3115). His formative ideas clearly exceeded the bounds of strict localism, and presented a holistic framework such that “sensorimotor processes become embedded in a network of connections that relate them in successively more complex ways to allow for performance of more and more nuanced and adaptive functions (Franz and Gillette, 2011).

1890William James

Soon after Hughlings-Jackson’s work was laid out, psychologist William James first used the term plasticity in  relation to the idea that the brain is not a fixed entity, but rather one that has the capacity to change itself. It was evident that James was influenced by Hughlings-Jackson, as he wrote about his views related to the brain and mind being from sensorimotor elements. In The Principles of Psychology, he wrote that plasticity “means the possession of a structure weak enough to yield to influence, but strong enough not to yield all at once… organic matter, especially nervous tissue, seems endowed with a very extraordinary degree of plasticity of this sort” (cited in Pascual-Leone, Amedi, Fregni & Merabet 2005).

Thus both Hughlings-Jackson and James, as early as the late 19th century, conceptualized the brain as a dynamic structure, capable of change. Yet, it would be nearly a century after their seminal writings before plasticity, in lieu of localization, would be widely recognized.

1906Santiago Ramon y Caja

Brodmann's Areas - Left Hemisphere

Figure 1.
Brodmann’s Areas—lateral view of the left hemisphere.

Santiago Ramon y Cajal was a leading neuroanatomist in the early 1900s (and Nobel Laureate in 1906), and was a proponent of the idea that the brain was incapable of change once development was complete (Stein, 2012). In particular, Cajal viewed the brain as a “predictable circuit and not as a diffuse network with unpredictable results” (Venkataramani, 2010). His views helped to solidify localism at the time, yet his impact and his ideas were far reaching well into today, and set the stage in many respects for our modern day understanding of neuroplasticity.

While Cajal was working to define the neurobiology of the brain, at nearly that same time, German anatomist Karbinian Brodmann was defining the cerebral cortex into 52 regions based on their histological characteristics. He published his work on cytoarchitecture in 1909, and his work is still often cited as many of the areas he identified correlate to key cortical functions (see Figure 1). For example, Area 4 relates to the primary motor cortex, Areas 41 and 42 encapsulate the auditory cortex, and Areas 3, 1 & 2 are the primary sensory cortex.

As the remainder of the 20th century marched along, the Doctrine was well established in the psyche of most neuroscientists of the time. There were, however, others who found evidence contrary to the Doctrine, many of whom had their work discredited or discounted. As Donald Stein (2012) noted:

“During the first half of the 20th century, some neuroanatomists who observed structural changes in the injured adult brain—now considered characteristic of neuronal repair, such as axonal or dendritic sprouting, or even neurogenesis—often reported such changes as artifacts of histological techniques rather than as evidence of CNS structural plasticity” (p. 162).

This unfortunate set of events, however, did not dissuade all practitioners of neuroscience. And for those who marched forward, the fruit of their labor was that in the end, the idea that the brain was capable of significant change was genuine.

1949Donald Hebb

One such practitioner was Donald Hebb who proposed that neurons adapt during the learning process. So if neuron A, fires, which connects to neuron B, causing it to fire, and this is done repeatedly, chemical changes alter the connection between A and B strengthening both. The result of this strengthened connection is ultimately the process of learning. This is now called Hebbian Theory, and has been informally christened as “Neurons that Fire Together, Wire Together.” Hebbian theory laid the groundwork for modern day forays into neuroplasticity, primarily because the theory provides that the structure of neurons can be altered by behavioral experience (Doidge, 2007).

1960Paul Bach y Rita

In the late 1960s Paul Bach y Rita introduced the idea of sensory substitution. In essence, Bach y Rita was the first to take the ideas of neuroplasticity and apply them in a meaningful, functional way for patients. He developed a machine (called the Tactile Vision Substitution System) whereby patients who were blind at birth sat in a chair against a bank of vibrating plates, which was connected to a camera. The camera sent signals to the plates causing them to vibrate in patterns connected to the tonal qualities of the object in the camera. The blind individuals’ brains soon interpreted these signals allowing them to see at a rudimentary level the objects despite their blindness. As a result of their training, they could “discriminate vertical, horizontal, diagonal and curved lines. They then learned to recognize combinations of lines (circles, squares, and triangles) and solid geometric forms. After approximately one hour of such training they are introduced to a ‘vocabulary’ of 25 common objects: a telephone, chair, cup, toy horse and others. With repeated presentations, the latency or time to recognition of these objects fall markedly; in the process, the students discover concepts such as perspective, shadows, shape distortion as a function of viewpoint, and apparent change in size as a function of distance” (Bach y Rita, Collins, Saunders, White and Scadden, 1969, p. 963). This work led Bach y Rita to note that “we see with our brains, not with our eyes.”


Geoffrey Raisman published an article in Brain Research which examined the question of whether the central nervous system is capable of re-organization at the anatomical level (Raisman, 1969). In a rat model, Raisman examined an area of the brain where two distinct afferent pathways (inputs from the body) led to the same cortical structure. He then cut one of the afferent pathways, to determine what, if any, change took place. What he found was that the fibers from the uncut pathway took over vacated synapses from the cut pathway. Raisman noted that the finding of reinnervation to the brain area “implies that the central nervous system can no longer be considered incapable of reconstruction in the face of damage. Anatomically, central synapse are labile, and this plasticity may not be restricted to lesion situations—it may play some part in learning.” Thus, he demonstrated unequivocally that synapses are far more malleable than previously understood.

Stein (2012) notes that this finding was one that turned the tide in the 1960s away from the Doctrine of Localization in favor of the idea that the brain can and does change.

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