Sensory Systems/Change of Sensory Processing Through Disuse
The idea that the functional and structural organization of the brain can change also in the adult brain existed for many decades. Already Ramon y Cajal stated in 1928 that neurons can regenerate after lesions (Stanisch & Nitsch, 2002). But only in the last two or three decades it has been possible to demonstrate what changes occur and how they occur.
These changes of the brain are referred as brain plasticity or neuroplasticity. Neuroplasticity can be divided in either functional or structural plasticity. Although the structure and function of the brain are of course connected, it is important to distinguish between these two concepts as they are differently measured and can occur independently (Buonomano & Merzenich, 1998).
Structural Neuroplasticity refers to changes in the brain tissue. These can be changes in the grey matter or in the white matter of the brain. Grey matter changes are mostly changes of density or volume. More precisely the thickness is often observed to be changed by experience, while the area of a region remains unchanged. The area seems to be mostly genetically determined. Although not all areas of the brain show the same heritability of grey matter density. In humans mostly frontal and perisylvian parts of the brain show a lower heritability in grey matter density than the rest of the brain (Thompson et al., 2001).
Density, volume, area and thickness of grey matter are measured in the living human brain most often by magnetic resonance imaging (MRI).
White matter changes can be also changes of volume, but are much more often changes of white matter integrity, like changes in fiber organization, the grade of myelinization or changes in axonal width (Zatorre et al., 2012). The integrity of white matter is thought to be determined by the diffusion tensor, which is measured in the living tissue by a method called diffusion tensor magnetic resonance imaging or for short diffusion tensor imaging (DTI). It’s one of the measurement protocols that can be used by MRI machines (Jones, 2008).
Functional Neuroplasticity refers to changes in function of brain areas or changes of activation patterns following experience or training. A brain area can change its function without changing its size. Equally an activation pattern can change without measurable changes in the structure of the brain tissue. A changed activation pattern means that some areas could be more active and other areas less active after training. Less activation doesn’t have to mean less performance. Less activation of an area can be caused because another maybe more specialized area is taking over, or that the less active area is just more effective after training. But just as well more activation often is thought to be due to higher proficiency after training (Jäncke, 2013).
The most common method to measure activation in the human brain is the blood-oxygen-level dependent (BOLD) contrast imaging, which is a method used in functional MRI (fMRI) and measures the relation of oxygenated and deoxygenated hemoglobin from which brain activity can be deduced (Arthurs & Boniface, 2002). In animals there are used invasive but much more precise methods like single-cell recordings with microelectrodes on the open skull.
Changes in the Visual Cortex
During maturation some brain functions go through a critical period. In the “critical period” the brain is especially sensitive to certain predetermined stimuli. If the nervous system doesn’t receive appropriate stimuli in this critical time window the function to process these stimuli will not develop normally. Later in life it will be difficult or even impossible to develop this function (Purves, 2008).
Acquisition of speech is maybe the best know phenomenon in humans which goes through a critical period. Another example is the imprinting of gooses on their mother shortly after birth.
Also the visual system goes through a critical period. For cats this time was found to be only a couple of days at the age of approximately four weeks. The same is the case for monkeys, but their critical phase lasts up to 6 months.
Deprivation of vision
The deprivation of visual inputs during the critical phase leads to a modification of the neuronal connectivity in the visual cortex. (Purves, 2008). These changes can be illustrated with the unbalanced development of the ocular dominance columns after vision deprivation of one eye. Ocular dominance columns respond preferentially to the input from one eye or the other. They lay in a stripped pattern on V1 and are most prominent in cortical layer 4 but also present in other layers. The stripes have a width of about 0.5mm. The columns can be visualized by injecting a radioactive amino acid tracer into one eye, which is subsequently transported to layer 4. In experiments with kittens one of their eyes was closed during the critical period (first three months after birth). If vision of one eye was deprived during the critical phases, the columns of the eye receiving visual stimulation take over the region of the deprived eye. Thus, the stripes of the stimulated eye become wider, at the expense of the deprived eye (Hubel and Wiesel, 1962). This implies that competitive interaction between both eyes can be found, based on the amount of received visual stimulation.
When both eyes were closed during the critical phase, the representation of both eyes in the ocular dominance columns remained balanced and vision was kept in both eyes. One fourth of the neurons in the visual cortex are predominantly stimulated by only one eye. When sight of one eye is deprived during the critical period, the normally functioning eye takes over. Nevertheless, tests have revealed that more peripheral cells in the retina or the geniculate layer of the closed eye still worked normally.
The principle of competitive interaction of both eyes during the critical period has important consequences for young children: a balanced stimulation of both eyes is required for a healthy development. The inputs of both eyes can be imbalanced due to birth defects or ocular injuries. If this imbalance does not heal during the critical phase this can lead to “amblyopia”, a permanently impaired vision, with poor binocular fusion, diminished depth perception and degraded acuity. (Purves, 2008).
Strabismus, sometimes also referred to as "lazy eye", is the improper function of one of the eyes and it can cause amblyopia. The dysfunction of one extraocular muscle can make it impossible to align both eyes and focus on one object. Strabismus can appear as "esotropia", where the gaze of the eyes cross, or "exotropia”, with a divergent gaze,. The resulting double vision leads to suppression of information from one eye. This can be compared to the deprivation of one eye as described above. In such a cases an early operation on the extraocular muscles is required, in order to assure a balanced development of the visual cortex.
Another disease which can lead to visual deprivation on one or both eyes is “cataracts”, a blurring of the lens of the eye and/or the cornea. This blurring can be caused by bacterial or parasitic infections (onchocerciasis), which often occur in tropical regions and affect millions of people. Especially in developing countries, this disease often remains untreated during the critical period, and subsequent restoration of vision can no longer establish binocular vision.
Regeneration possibilities of the visual system
The brain of young children is much more plastic than a mature brain. This is particularly valid for the motor- and somatosensory areas, and to a certain degree also for the visual system. This plasticity includes not only the modifications mentioned above, but also the possibility to restore function after brain damage. The capability of plasticity, however, depends on the location and the type of lesion as discussed below. For the recovery of vision, we can discriminate between conscious and unconscious vision. The recovery of full conscious vision requires a functioning pathway between retina and the primary visual cortex (Felleman and Van Essen, 1991). To some degree vision can be revived in form of unconscious vision when the primary visual cortex is damaged. Unconscious vision includes the sensitivity to motion, shape, and color. There is evidence that unconscious vision can be better developed if the damage happens in early childhood (Mercuri et al., 2003).
Nevertheless when vision is deprived since birth then regaining vision even for young children is difficult but not impossible. Pawan Sinha an indian scientist and professor for vision and computational neuroscience at the MIT in Cambridge founded the Prakash project. This initiative has the goal to find and treat children in India with cataracts and corneal opacities. Since the year of its foundation in 2003 already 40'000 children have been screened and over 400 were provided with surgical treatment (Sinha et al., 2013). From this project emerged new insights to the development of the human visual system. Immediately after surgery and onset of sight formerly congenital blind children could not visually recognize an object they have felt with their hands just before. Thus the authors conclude that there is no innate connection between touch and sight, that correlating what we see with what we touch must be learned first. Just a week after the surgery the children could already relate the seen with the touched objects. Not only relating seen objects with touched objects, also object recognition is very poor right after onset of sight, especially when objects are not moving and overlapping. Motion seems to be instrumental in segregating different objects. Apparently the ability to regain vision after congenital blindness is also maintained in adults. Ostrovsky et al. (2009) are reporting a case of a 29 year old male patient who was given a refractory correction and regained vision partially. After one month he could already distinguish different non-moving, overlapping objects.
Although this are impressive results, it remains unclear to which degree these children can be really considered as congenital blind as many of them are not completely blind and most of them haven't been born blind, but lost sight in early childhood.
Also healthy, seeing adults got the capacity for adaptation and plasticity in the visual system. One study was conducted with 24 volunteers. They were split in to two groups. One group was assigned to a juggling training, the other group was used as a control and didn't get any training. All subjects were inexperienced in juggling at the time they were recruited for the study. The subjects in the juggler group were given 3 months to learn to juggle with 3 balls. They were considered to have reached the level of a skilled performer, when they could sustain juggling for at least 60 seconds. MRI brain scans were performed before the training started, when subjects became skilled performers, and 3 months after the last training session. Before training the two groups showed no differences. The juggler group showed a significant expansion in grey matter in V5/MT bilaterally and in the left posterior intraparietal sulcus (IPS). Three months after training the grey matter was significantly reduced again in V5 and in IPS but still over the level of the pretraining scan (Draganski et al., 2004).
Cross-modal plasticity is the modification of neuronal responsiveness to a sensory input after the deprivation of its primary sensory input. An illustrative example is the rodent's use of the whiskers. The whiskers help these animals to orientate in space, especially in the dark. If vision is deprived in early age, it can be observed that the whiskers grow longer, which should enhance the orientation of the blind rodent (Rauschecker et al., 1992). The same enhancement of complementary sensory systems, e.g. the auditory and tactile system, can be found after visual deprivation in humans.
Experiments on the ability of sound localization have been performed on healthy and blind cats. These tests revealed that the blind animals were more accurate at localizing sound. Blind cats make a typical vertical head movement in order to localize the source of the sound. This compensatory process is assumed to help improve the general sound perception and localization (Rauschecker, 1995).
During an investigation with humans, auditory stimuli were given to sighted and blind people. While the occipital cortex in sighted subjects didn't show any response to the auditory stimuli, in the blind subjects the occipital cortex was active. This phenomena was confirmed by another investigation, which used transcranial magnetic stimulation (TMS) to inhibit brain activity in the occipital cortex. Such the performance of sound localization of the blind decreased, whereas the ability in pitch or intensity recognition was unchanged. The localization accuracy correlated in blind subjects positively with the degree of occipital activation. However, this intervention revealed no effects for normally sighted subjects in their auditory perception (Collignon et al., 2007).
Another fascinating example is echolocation. There are some blind people which can actively echolocate. They learned to produce clicks with their tongues and mouths and interpret the reflected sound, such that they can orientate and define distances from different objects in the environment. Such echolocating clicks are typically short (10 ms) and spectrally broad. Early and late blind can achieve the ability of echolocation. But it seems that only congenital and early blind have a widespread activation in the occipital cortex around the calcarine sulcus and not late blind subjects (Thaler et al., 2011).
We can conclude that plasticity is possible until adulthood, though there is a critical period also for the visual system. When the occipital cortex isn't visually stimulated in this critical period, then at least some functions of the visual system will never develop. And possibly the visual cortex will be even assigned to a completely different function like echolocating. But to which degree exactly the visual cortex remains plastic after the critical period, is still under debate.
Changes in the Somatosensory Cortex
One of the first experiments on functional plasticity in the somatosensory cortex was done by Merzenich et al. (1984) on primates. First they defined with microelectrodes the cortical representations of the fingers in the hand area of adult owl monkeys. Then they amputated the monkey's middle fingers and mapped the hand area again 2-8 months after the amputation. They found that only after two months the representations of adjacent digits expanded into the area formerly representing the middle finger. Thus the surrounding skin got a magnified representation on the cortex, while at the same time the receptive field sizes of the surrounding skin shrunk. It seems that recruiting more neurons for the same part of skin gave way to smaller sizes of the receptive fields.
Similarly when two fingers of owl monkey where surgically connected, and such the input to this two digits were highly correlated, the border between the areas representing the two fingers vanished (Clark et al., 1988). On the other hand when the monkey's fingers where exposed to a finer and more complex stimulation, using a corrugated rotating disc, after 80 days the area representing the stimulated finger widened. Possibly because a finer grained stimulation needed smaller receptive fields, thus more neurons needed to be recruited and the finger area grew (Jenkins, Merzenich & Recanzone, 1990).
On humans a first and impacting insight to functional plasticity was brought by Ramachandran (1993). He found that some patients who got an upper limb amputated felt like somebody was touching their inexistent arm when he stimulated their ipsilateral face with a cotton bud. He was even able to draw a map of the former limb on the patient's cheek and jaw. This representation of the amputated extremity on the face had well defined borders and stayed stable over several weeks. As the face area on the somatosensory cortex is just next to the hand area it's most likely that the face area is recruiting the neurons formerly receiving input from the amputated limp, just as in the experiment with the owl monkeys. In the process of reorganization some neurons will start to respond to the incoming sensory stimulation from the face while still being inbound to the former hand network, causing a representation of the amputated limb on the ipsilateral face. This representation mostly disappears again after some time when the recruiting process is completed (Jäncke, 2013). Possibly also the phantom limb sensation has to do with this process. Some patients experience a sensation as if their amputated limb still would be there, called “phantom limb”. Sometimes this sensation can be quite painful. Some experience painful involuntarily clenching spasms in their phantom limb (Ramachandran & Rogers-Ramachandran, 1996). Often when the transitional period is over and the former limb neurons are completely integrated into other areas like the face are, the sensation of the phantom limb disappears. But some patients suffer from persistent phantom limb sensations. A often applied therapy in these cases is mirror therapy, where a mirror is placed vertically in front of the patients such that in the mirror the intact limb is superimposed on where the amputated limb would be. Although mirror therapy is not helping all patients (Rothgangel et al., 2011), some profit, for example by opening their healthy hand helps them open mentally their phantom hand in the mirror, giving relieve from the clenching spams. Without the mirror they were not able to relax the phantom hand (Ramachandran & Rogers-Ramachandran, 1996).
But not only functional also structural changes can be observed after the amputation of a limb. Draganski et al. (2006) found that patients with an amputated limb had significantly less gray matter in the thalamic ventral posterolateral nucleus than age-matched healthy controls. Moreover the time since the amputation correlated significantly with the loss of grey matter in the thalamus (r=.39).
Gaining through Training
Plenty of studies also were conducted on musicians. Musicians train very intensive and often a life-long, hence they are the ideal subjects for cross-sectional studies. String players for example have a bigger area for their fingers of the left hand on the somatosensory cortex than non-musicians have. And the earlier a musician started in his life the training the bigger is the area of his non-dominant hand (Elbert et al., 1995).
Pianists performing a tapping task showed considerably lesser activation of primary and secondary motor areas than in non-musicians. A possibility to explain this result is that the intensive and long lasting hand skill training of the pianists enhanced the efficiency of the motor areas. Thus the same task activates in highly trained subjects less neurons than in untrained ones (Jäncke et al., 2000). Musicians also undergo various alterations of the auditory cortex (more about this in the next section).
An often expressed critic of cross-sectional studies is that it isn't possible to decide, if the differences in certain brain areas encountered in trained people are caused by the training or if they just decided to train a certain task (e.g. become a musician) because they were specially able for this task and the respective brain area was already before the training more effective or larger. Only longitudinal studies could bring light into that.
One longitudinal study was conducted with 10 right-handed patients with an injury of the upper right limb which required an immobilization of the limb for at least two weeks. Within 2 days after the injury a brain scan was performed and the cortical thickness measured. After 16 days of immobilization a second scan was done and found that there was a significant grey matter decrease in the left primary motor areas and in the left somatosensory areas. Further also the integrity of the corticospinal tract was significantly decreased (Langer et al., 2012).
In another study the dominant hands of 14 right-handed patients with writer's cramp have been immobilized for 4 weeks. After immobilization the patients had to train their dominant hand again for 8 weeks. Also here an MRI-scan revealed a significant lower grey matter density in the contralateral primary motor hand area after the immobilization phase. The re-training reversed the effects and grey matter density increased again (Granert et al.,2011).
Bezzola et al. (2011) looked at golf novices between the age of 40 and 60 years. And found after 40 hours of individual training an significant increase in grey matter in various parts of the brain like in the motor and premotor cortex or the intraparietal sulcus. Training intensity correlated with the percentage of grey matter increase. And also a change of the activation pattern while mentally rehearsing a golf swing could be observed. The dorsal premotor cortex was after training significantly less activated ([Bezzola et al., 2012).
Rehabilitation after Brain Lesions
Finally, special consideration deserve rehabilitation processes after brain lesions. Before described plasticity abilities apply also for rehabilitation but there are mainly two big challenges. First, are lesions too big so that entire functions are completely eradicated, there is till now no possibility to bring the function back. Second, partially preserved functions are often suppressed by the contralateral healthy area with the same or similar function. For example, is the left side of the body partially paralyzed, then the healthy left hemisphere will try to take control as there is no inhibition from the damaged right hemisphere to the left one. Thus the healthy hemisphere will inhibit the damaged hemisphere and rehabilitation is hindered, rewiring of the still healthy neurons on the damaged side is impeded. A possibility to overcome this is by inhibiting the healthy hemisphere with TMS or transcranial direct-current stimulation (tDCS) during or just before rehabilitative training (Jäncke, 2003).
In summary, it can be said that using an extremity more or training a certain task will have a positive effect on corresponding brain areas, leading eventually to more efficiency more grey matter and better integrity of white matter. Not using a limb, not training an ability will have the contrary effect. At the most extreme point of amputated limbs brain regions will be overtaken by other functions.
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