Cortical remapping

Last updated December 04, 2021

Cortical remapping, also referred to as cortical reorganization, is the process by which an existing cortical map is affected by a stimulus resulting in the creating of a 'new' cortical map. Every part of the body is connected to a corresponding area in the brain which creates a cortical map. When something happens to disrupt the cortical maps such as an amputation or a change in neuronal characteristics, the map is no longer relevant. The part of the brain that is in charge of the amputated limb or neuronal change will be dominated by adjacent cortical regions that are still receiving input, thus creating a remapped area.^[1] Remapping can occur in the sensory or motor system. The mechanism for each system may be quite different.^[2] Cortical remapping in the somatosensory system happens when there has been a decrease in sensory input to the brain due to deafferentation or amputation, as well as a sensory input increase to an area of the brain.^[1] Motor system remapping receives more limited feedback that can be difficult to interpret.

History

Localization

Wilder Penfield, a neurosurgeon, was one of the first to map the cortical maps of the human brain.^[3] When performing brain surgeries on conscious patients, Penfield would touch either a patient's sensory or motor brain map, located on the cerebral cortex, with an electric probe to determine if a patient could notice either a specific sensation or movement in a particular area on their body. Penfield also discovered that the sensory or motor maps were topographical; areas of the body adjacent to one another would likely be adjacent on the cortical maps.^[3]

Due to Penfield's work, the scientific community concluded that the brain must be fixed and unchangeable because a specific area of the brain corresponds to a particular point on the body. However, this conclusion was challenged by Michael Merzenich, whom many call "the world's leading researcher on brain plasticity."^[3]

Plasticity

In 1968, Merzenich and two neurosurgeons, Ron Paul and Herbert Goodman, conducted an experiment to determine effects on the brain after a large bundle of peripheral nerves in adolescent monkeys' hands were cut and began to regenerate again.^[3]^[4]^[5] They knew that the peripheral nervous system could regenerate itself and sometimes during that process the neurons would 'rewire' themselves by accident. These 'wires' would accidentally connect to a different axon, stimulating the wrong nerve. This resulted in a "false localization" sensation; when the patient was touched on a specific area of the body, that touch was actually felt on a different part of the body than expected.

To better understand this phenomenon in the brain, they used micro-electrodes to micromap the monkey's cortical map of its hand. The peripheral nerves were cut and sewn close together to observe evidence of axon 'wires' crossing during regeneration. After seven months, the cortical map of the monkeys' hands were remapped and it was found that the map appeared to be essentially normal, with no 'wire crossing' as expected. They concluded if a cortical map was able to "normalize" itself when stimulated with an irregular input that the adult brain must be plastic.

This experiment helped inspire questioning of the scientific "truth" that the adult brain is fixed and cannot continue to change outside of the critical period, especially by Merzenich. Later in his career, Merzenich conducted an experiment that highlighted the existence of cortical remapping and neuroplasticity. Merzenich and fellow neuroscientist, Jon Kaas, cut the median nerve of a monkey's hand, which delivers sensation to the middle of the hand, to see what the median nerve map would look like when all input was cut off after a period of two months.^[6] When the hand was remapped, it was found that when the middle of the hand was touched no activity occurred at the median nerve location. But when the sides of the monkey's hand were touched, activity was found in the median nerve location on the map. This meant that cortical remapping had occurred at the median nerve; the nerves that correlated to the outsides of the monkey's hand had remapped themselves to take over the 'cortical real estate' that was now available due to the median nerve being disconnected.^[3]^[6]

Sensory system

Sensory system remapping can potentially self-organize due to the spatiotemporal structure of input.^[2] This means that the location and timing of the input is critical for remapping in the sensory system. A study by Gregg Recanzone demonstrates this by seeing if a monkey could distinguish between a stimulus of high and low frequency vibrations, delivered to the tip of its finger at a fixed location. Over time, the monkey got better at identifying the differences in vibration frequency. When the finger was mapped, the map was found to be degraded and unrefined. Because the stimuli were done at a fixed location, everything was excited and therefore selected, resulting in a crude map. The experiment was conducted again except, the location of the high and low vibrations were varied at different parts of the monkey's fingertip. As before, the monkey improved over time. When the monkey's finger was remapped it was found that the crude map from before had been replaced with an elegant map of the fingertip showing all the different places stimulation had occurred on different locations of the fingertip.^[7] This study showed that over a period of time, a map could be created from a localized stimulus and then altered by a location variable stimulus.

Motor system

Motor system remapping, as compared to sensory system remapping, receives more limited feedback that can be difficult to interpret.^[2] When looking at motor system maps, you find that the last pathway for movement to occur in the motor cortex does not actually activate the muscles directly but causes decreased motor neuron activity. This means, there is a possibility that remapping in the motor cortex can come from changes in the brainstem and spinal cord, locations that are difficult to experiment on, due to challenging access.^[2]

A study done by Anke Karl helps demonstrate why the motor system may be dependent on the sensory system in regard to cortical remapping. The study found a strong connection between motor and somatosensory cortical remapping after amputation and phantom limb pain. The study assumed that somatosensory cortex reorganization can affect plasticity in the motor system because stimulation of the somatosensory cortex prompts long term potentiation in the motor cortex. The study concluded that reorganization of the motor cortex may only be subsidiary to cortical changes in the somatosensory cortex.^[8] This helps support why feedback to the motor system is limited and difficult to determine for cortical remapping.

Application

Cortical remapping helps individuals regain function from injury.

Phantom limbs

Phantom limbs are sensations felt by amputees that make it feel like their amputated extremity is still there.^[9] Sometimes amputees can experience pain from their phantom limbs; this is called phantom limb pain (PLP).

Phantom limb pain is considered to be caused from functional cortical reorganization, sometimes called maladaptive plasticity, of the primary sensorimotor cortex. Adjustment of this cortical reorganization has the potential to help alleviate PLP.^[10] One study taught amputees over a two-week period to identify different patterns of electrical stimuli being applied to their stump to help reduce their PLP. It was found that the training reduced PLP in the patients and reversed the cortical reorganization that had previously occurred.^[10]

However, a recent study by Tamar R. Makin suggests that instead of PLP being caused by maladaptive plasticity, it may actually be pain induced.^[11] The maladaptive plasticity hypothesis suggests that once afferent input is lost from an amputation, cortical areas bordering the same amputation area will begin to invade and take over the area, affecting the primary sensorimotor cortex, seeming to cause PLP. Makin now argues that chronic PLP may actually be 'triggered' by "bottom-up nociceptive inputs or top-down inputs from pain-related brain areas" and that the cortical maps of the amputation remain intact while the "inter-regional connectivity" is distorted.^[11]

Stroke

The mechanisms involved in stroke recovery mirror those related to brain plasticity. Tim H. Murphy describes it as, "Stroke recovery mechanisms are based on structural and functional changes in brain circuits that have a close functional relationship to those circuits affected by stroke."^[12]

Neuroplasticity after a stroke is enabled by new structural and functional circuits that are formed through cortical remapping. A stroke occurs when there is not enough blood flow to the brain, causing debilitating neurological damage. The tissue that surrounds the infarct (stroke damaged area) has reduced blood flow and is called the penumbra. Though the dendrites in the penumbra have been damaged due to the stroke, they can recover during the restoration of blood flow (reperfusion) if done within hours to a few days of the stroke due to time sensitivity. Due to reperfusion in the peri-infarct cortex (found next to the infarct), the neurons can help with active structural and functional remodelling after stroke.^[12]

Cortical remapping is activity-dependent and competitive. The recovering peri-infarct regions that have bad circuits are competing with healthy tissue for cortical map space. An in vivo study by Murphy was done using mice to help identify the sequence and kinetics of the peri-infarct cortical remapping after stroke. The study showed that eight weeks after a stroke had occurred in the forelimb sensory cortex of a mouse, the 'surviving' portion was able to promptly relay enhanced sensory signals to the motor cortex, which resulted in the remapping of sensory function. The mouse that experienced a stroke had remapped responses that lasted longer and spread farther from the motor cortex than those of the control. This means that recovery of the sensorimotor functions after stroke and cortex remodeling suggests changes in the temporal and spatial spread of sensory information.^[12]

A model for stroke recovery suggested by Murphy, involves beginning with homeostatic mechanisms (neurons receive proper amount of synaptic input) at the start of stroke recovery. This will restart activity in stroke-affected areas through structural and functional circuit changes. Activity-dependent synaptic plasticity can then strengthen and refine circuits when some of the sensory and motor circuitry is spared. Regions of the brain with partial function can have their circuits recover over a few days to weeks through remapping.^[12]

Cortical remapping after a stroke is comparable to initial brain development. For example, remapping that occurs in motor recovery after a stroke is similar to an infant learning skilled movement patterns. Though this is very important information on developing recovery plans for stroke patients, it is important to keep in mind that the circuitry of a stroke patient is quite different from that of a developing brain, and could be less receptive.^[12]

Related Research Articles

A phantom limb is the sensation that an amputated or missing limb is still attached. Approximately 80 to 100% of individuals with an amputation experience sensations in their amputated limb. However, only a small percentage will experience painful phantom limb sensation. These sensations are relatively common in amputees and usually resolve within two to three years without treatment. Research continues to explore the underlying mechanisms of phantom limb pain (PLP) and effective treatment options.

Vilayanur Subramanian Ramachandran is an Indian-American neuroscientist. Ramachandran is known for his wide-ranging experiments and theories in behavioral neurology, including the invention of the mirror box. He is a Distinguished Professor in UCSD's Department of Psychology, where he is the director of the Center for Brain and Cognition.

The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus.

Cortical maps are collections (areas) of minicolumns in the brain cortex that have been identified as performing a specific information processing function.

Barrel cortex Region of the somatosensory cortex in some rodents and other species

The barrel cortex is a region of the somatosensory cortex that is identifiable in some species of rodents and species of at least two other orders and contains the barrel field. The 'barrels' of the barrel field are regions within cortical layer IV that are visibly darker when stained to reveal the presence of cytochrome c oxidase and are separated from each other by lighter areas called septa. These dark-staining regions are a major target for somatosensory inputs from the thalamus, and each barrel corresponds to a region of the body. Due to this distinctive cellular structure, organisation, and functional significance, the barrel cortex is a useful tool to understand cortical processing and has played an important role in neuroscience. The majority of what is known about corticothalamic processing comes from studying the barrel cortex, and researchers have intensively studied the barrel cortex as a model of neocortical column.

Mirror therapy (MT) or mirror visual feedback (MVF) is a therapy for pain or disability that affects one side of the patient more than the other side. It was invented by Vilayanur S. Ramachandran to treat post-amputation patients who suffered from phantom-limb pain (PLP). Ramachandran created a visual illusion of two intact limbs by putting the patient's affected limb into a "mirror box," with a mirror down the center.

Phantom pain is a perception that an individual experiences relating to a limb or an organ that is not physically part of the body. Limb loss is a result of either removal by amputation or congenital limb deficiency. However, phantom limb sensations can also occur following nerve avulsion or spinal cord injury.

Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. These changes range from individual neuron pathways making new connections, to systematic adjustments like cortical remapping. Examples of neuroplasticity include circuit and network changes that result from learning a new ability, environmental influences, practice, and psychological stress.

The human secondary somatosensory cortex is a region of cortex in the parietal operculum on the ceiling of the lateral sulcus.

Silver Spring monkeys Macaques used in neuroplasticity research; subjects of an animal-cruelty court case

The Silver Spring monkeys were 17 wild-born macaque monkeys from the Philippines who were kept in the Institute for Behavioral Research in Silver Spring, Maryland. From 1981 until 1991, they became what one writer called the most famous lab animals in history, as a result of a battle between animal researchers, animal advocates, politicians, and the courts over whether to use them in research or release them to a sanctuary. Within the scientific community, the monkeys became known for their use in experiments into neuroplasticity—the ability of the adult primate brain to reorganize itself.

The zona incerta (ZI) is a horizontally elongated region of gray matter in the subthalamus below the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord.

The phantom eye syndrome (PES) is a phantom pain in the eye and visual hallucinations after the removal of an eye.

Michael Matthias Merzenich is a professor emeritus neuroscientist at the University of California, San Francisco. His contributions to the field are numerous. He took the sensory cortex maps developed by his predecessors and refined them using dense micro-electrode mapping techniques. Using this, he definitively showed there to be multiple somatotopic maps of the body in the postcentral sulcus, and multiple tonotopic maps of the acoustic inputs in the superior temporal plane.

Body schema is a concept used in several disciplines, including psychology, neuroscience, philosophy, sports medicine, and robotics. The neurologist Sir Henry Head originally defined it as a postural model of the body that actively organizes and modifies 'the impressions produced by incoming sensory impulses in such a way that the final sensation of body position, or of locality, rises into consciousness charged with a relation to something that has happened before'. As a postural model that keeps track of limb position, it plays an important role in control of action. It involves aspects of both central and peripheral systems. Thus, a body schema can be considered the collection of processes that registers the posture of one's body parts in space. The schema is updated during body movement. This is typically a non-conscious process, and is used primarily for spatial organization of action. It is therefore a pragmatic representation of the body’s spatial properties, which includes the length of limbs and limb segments, their arrangement, the configuration of the segments in space, and the shape of the body surface. Body schema also plays an important role in the integration and use of tools by humans.

The somatosensory system is a part of the sensory nervous system that is associated with the sense of touch, but includes parallel receptors and nerve pathways for the sensations of temperature, body position and movement, and pain. This complex system of sensory neurons, and neural pathways responds to changes at the surface of, or inside, the body. The axons of sensory neurons connect with, or respond to, various receptor cells. These sensory receptor cells are activated by different stimuli such as heat and nociception, giving a functional name to the responding sensory neuron, such as a thermoreceptor which carries information about temperature changes. Other receptor types include mechanoreceptors, chemoreceptors, and nociceptors which send signals along a sensory nerve to the spinal cord, where the signals may be processed by other sensory neurons, and then relayed to the brain for further processing. Sensory receptors are found all over the body including the skin, epithelial tissues, muscles, bones and joints, internal organs, and the cardiovascular system.

Sensory maps are areas of the brain which respond to sensory stimulation, and are spatially organized according to some feature of the sensory stimulation. In some cases the sensory map is simply a topographic representation of a sensory surface such as the skin, cochlea, or retina. In other cases it represents other stimulus properties resulting from neuronal computation and is generally ordered in a manner that reflects the periphery. An example is the somatosensory map which is a projection of the skin's surface in the brain that arranges the processing of tactile sensation. This type of somatotopic map is the most common, possibly because it allows for physically neighboring areas of the brain to react to physically similar stimuli in the periphery or because it allows for greater motor control.

Sensory stimulation therapy (SST) is an experimental therapy that aims to use neural plasticity mechanisms to aid in the recovery of somatosensory function after stroke or cognitive ageing. Stroke and cognitive ageing are well known sources of cognitive loss, the former by neuronal death, the latter by weakening of neural connections. As SS implies a patient will have a desired sense stimulated in a predetermined fashion at a known frequency. It has been found that this technique can be used to reduce as much as 30 years of cognitive ageing, and can both improve two point discrimination thresholds and also impair them.

Restorative neurology is a branch of neurology dedicated to improving functions of the impaired nervous system through selective structural or functional modification of abnormal neurocontrol according to underlying mechanisms and clinically unrecognized residual functions. When impaired, the body naturally reconstructs new neurological pathways and redirects activity. The field of restorative neurology works to accentuate these new pathways and primarily focuses on the theory of the plasticity of an impaired nervous system. Its main goal is to take a broken down and disordered nervous system and return it to a state of normal function. Certain treatment strategies are used to augment instead of fully replace any performance of surviving and also improving the potential of motor neuron functions. This rehabilitation of motor neurons allows patients a therapeutic approach to recovery opposed to physical structural reconstruction. It is applied in a wide range of disorders of the nervous system, including upper motor neuron dysfunctions like spinal cord injury, cerebral palsy, multiple sclerosis and acquired brain injury including stroke, and neuromuscular diseases as well as for control of pain and spasticity. Instead of applying a reconstructive neurobiological approach, i.e. structural modifications, restorative neurology relies on improving residual function. While subspecialties like neurosurgery and pharmacology exist and are useful in diagnosing and treating conditions of the nervous system, restorative neurology takes a pathophysiological approach. Instead of heavily relying on neurochemistry or perhaps an anatomical discipline, restorative neurology encompasses many fields and blends them together.

Tactile hallucination is the false perception of tactile sensory input that creates a hallucinatory sensation of physical contact with an imaginary object. It is caused by the faulty integration of the tactile sensory neural signals generated in the spinal cord and the thalamus and sent to the primary somatosensory cortex (SI) and secondary somatosensory cortex (SII). Tactile hallucinations are recurrent symptoms of neurological diseases such as schizophrenia, Parkinson's disease, Ekbom's syndrome and delerium tremens. Patients who experience phantom limb pains also experience a type of tactile hallucination. Tactile hallucinations are also caused by drugs such as cocaine and alcohol.

Limb telescoping is the progressive shortening of a phantom limb as the cortical regions are reorganized following an amputation. During this reorganization, proximal portions of the residual limb are perceived as more distal parts of the phantom limb. Such effect is responsible for increased phantom pain due to the discrepancy between the patient’s body perception and their actual body. This effect may last from weeks up to years after post-amputation.

References

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