|Nigel Daw (2009), Scholarpedia, 4(1):6572.||doi:10.4249/scholarpedia.6572||revision #56504 [link to/cite this article]|
Critical Period is a period during the early life of an animal when some property develops rapidly, and is most susceptible to alteration by the environment. Everybody knows that children learn languages most rapidly when young, and that it is more difficult when they become adult. Another famous example is imprinting in birds, where a newly born chick will follow the first animal seen after birth, even if it is not its mother, and belongs to a different species (Spalding, 1873). Human infants are also born with the ability to distinguish sounds in different languages, and lose some of this ability between six and twelve months when they start mouthing their own language (Werker et al., 1981). Critical periods have been most extensively studied in the visual system, with experiments in humans and several different mammalian species, looking at both the phenomena and the mechanisms, so that will be the subject of this article.
Critical period in vision
In the visual system, properties develop over the first few years of life, and may be disrupted during this time by alterations of the optical input, or motor control of the eyes. This is due to changes in the connections of neurons in the visual cortex. If the optical or motor problem is alleviated early enough, the deficit can be reversed. However, the period of development, the period during which disruption is effective, and the period during which recovery can be obtained are overlapping, but not always identical (Daw, 2003). The term critical period is most often used to refer to the period during which disruption is effective.
Critical periods in the visual system depend on the property being studied, the strength or duration of the deprivation, the technique used for measurement, the level of the visual system being investigated, and the visual history of the animal. Thus one cannot talk about a single critical period. One has to talk about the critical period for (for example) ocular dominance after monocular deprivation of 10 days duration assayed by single unit recordings in the visual cortex of the cat. What follows is a discussion of these issues.
Critical period for monocular deprivation
The critical period most studied is the critical period for ocular dominance after monocular deprivation (Hubel & Wiesel, 1970). This is usually done by suturing the eyelids of one eye shut (Wiesel & Hubel, 1963). The critical period, measured in primary visual cortex with single unit recordings, lasts from about 3 weeks to several months of age in the cat (Fig. 1; Daw, 1994). At the height of susceptibility, about 4-5 weeks of age, a day or two of deprivation will have an effect. At several months of age, a month or more is required. No change in the physiology of cells is seen in the retina, and little in the lateral geniculate nucleus. The main effect occurs in primary visual cortex, which is the first stage at which cells with binocular input are found, and there is a profound effect on the ocular dominance of the cells. In the most extreme cases, there are no cells at all driven by the deprived eye.
Cats reared in the dark have a critical period that starts later, and ends later (Fig. 2; Mower, 1981). Thus, a dark-reared cat at 6 weeks of age is less susceptible to monocular deprivation than a normal cat, and a dark-reared cat at 12-16 weeks of age is more susceptible. This has been useful in evaluating factors that are related to susceptibility, alias plasticity, and distinguishing them from factors that simply increase or decrease with age, and are affected by dark-rearing in the same way at all ages.
Monocular deprivation has been carried out in a number of species (cat, rat, mouse, ferret, macaque and humans with stimulus deprivation). In all these species, the critical period starts close to eye opening, peaks fairly soon after that, and declines from then until some time around puberty. However, some effect can be seen in the adult rat using visually evoked potentials as an assay, and a light anesthetic such as urethane. Reorganization in the adult visual cortex is also seen after a more drastic manipulation – a large lesion in the retina, which abolishes all input from that area.
The effect of monocular deprivation is larger at higher levels of the system. As already mentioned, there is no effect in the retina, and little in the lateral geniculate nucleus. Within the primary visual cortex, the effect is smaller in layer IV, where the input from lateral geniculate comes in, and larger in layers II, III, V, and VI, to which layer IV projects.
Critical periods for different properties
There are two pathways in the visual system. One is known as the P pathway, and goes through the parvocellular layers of the lateral geniculate nucleus to layer IVCbeta in striate cortex, leading to layers II/III, V2, V4 and ventral areas in the temporal cortex. It deals with fine acuity, color, and analysis of form. The other is known as the M pathway, and goes through the magnocellular layers of the lateral geniculate nucleus to layer IVCalpha in striate cortex, leading to layer IVB, V2, MT, and dorsal areas in the parietal cortex. It deals with movement and analysis of position in space.
There are different critical periods for these two pathways. This is shown by using monocular deprivation in the macaque, and changing the eye closed from right to left (reverse suture) at 3 weeks of age. A tracer is then injected into the right eye, and the width of the ocular dominance columns measured in layer IV of striate cortex. The right eye columns are wider in layer IVCbeta because this layer is still plastic at 3 weeks of age, and the left eye columns are wider in layer IVCalpha, because the critical period for this layer is over at this age (Fig. 3; LeVay et al., 1980). Presumably the movement pathway gets set in place earlier than the form and color pathway.
A difference has also been found in the cat. In one set of experiments, reverse suture was performed at different ages, and ocular dominance assayed. The percentage of cells dominated by the eye open second dropped to the percentage seen in normal animals at about 7 weeks of age (Fig. 4; Blakemore & Van Sluyters, 1974). In another set of experiments, animals were reared in a drum continually rotating around them, and the direction of rotation was reversed at different ages in different animals. The percentage of cells preferring the direction seen second dropped to the normal percentage at about 4 weeks of age (Daw & Wyatt, 1976). The conclusion is that direction selectivity gets set in place earlier than ocular dominance – a point that may be important for the development of stereopsis, where the direction and orientation selectivity needs to be coordinated between the two eyes before disparity sensitivity is fully developed. Moreover, although the periods for development and disruption are different, as pointed out above, the periods for the development of ocular dominance, orientation selectivity, and direction selectivity in the ferret follow different time courses (Katz & Crowley, 2002; White & Fitzpatrick, 2007).
Critical periods in humans
Critical periods in humans are of particular interest, because of the large number of people (2-4% of the population) who suffer from optical deficits in the eye or motor deficits of the eye movement system. The most common deficits are strabismus and anisometropia. Strabismus is a problem in the eye movement system where the two eyes look in different directions. As a result, the image falls on non-corresponding points of the two retinae. This leads to deficits in stereoscopic depth perception, and to amblyopia (dull sight, or poor vision) in the eye that is not looking straight ahead. Anisometropia is where one eye is focused at different distance from the other, also leading to mismatched images on the two retinas. Less of a problem is astigmatism, where a cylindrical component in the cornea results in acuity along one axis being better than along the perpendicular axis. Rare, but much more of a problem, is stimulus deprivation where the image in one or both eyes is degraded or absent due to a cataract, or patching after surgery.
The study that visualizes the critical period most comprehensively is a compilation of cases of stimulus deprivation from the literature (Fig. 5; Vaegan & Taylor, 1979). Children who have unilateral cataract between 6 months and two years of age have acuity less than 1% of normal, and a cataract any time before 5 years of age leads to legal blindness (less than 10% of normal). The deficit in a patient treated at a few months of age was less than those in patients suffering between a few months and 2-3 years. Little effect was seen after 9 years of age. The critical period for strabismus and anismetropia has been defined less quantitatively, but there is general agreement that it ends around 8 years of age. Thus the critical period adheres to the general rule that it lasts from soon after eye opening to some time around puberty, although no causal relationship has been established.
Recovery from these deficits depends on the treatment, and the nature of the deficit. Treatments include patching the good eye for much but not all of the time, straightening the eyes or removing the cataract, providing any optical correction needed, and encouraging exercises and visual stimulation. Substantial recovery is seen if all of these are pursued and the child cooperates. It is most difficult in stimulus deprivation and strabismus, less difficult in anisometropia, and not too difficult in astigmatism. Indeed, if the treatment includes refractive correction, alignment, and visual therapy in cases of anisometropia, almost total recovery is seen (Fig. 6; Wick et al., 1992). Moreover, recovery can be obtained long after the critical period for causation of the deficit is over, emphasizing the point that there are different critical periods for different aspects of visual properties. A review of the literature shows a number of good results in teenagers, and some in adults. The patients shown in figure 6 ranged in age from 16 to 46 years of age.
An interesting and unresolved problem concerns the critical period for stereopsis after one of these optical or motor deficits. Stereo develops very rapidly between 4 and 6 months of age, and more slowly after that up to 5-6 years of age. Stereo is, of course, severely disrupted by any manipulation that prevents the two eyes from looking at the same object, particularly strabismus. Recovery of fine stereopsis is difficult after 6 months of age, and almost impossible after 2 years of age, although there are dramatic exceptions such as the case of Stereo Sue, who recovered stereopsis at the age of 48 (Sacks, 2006).
Some of the mechanisms for plasticity in ocular dominance changes are discussed in Ocular Dominance. The whole process, as might be expected, is driven by electrical activity coming from the retinas. There are a number of factors that are more abundant or more active during the critical period. These include NMDA receptors and components of the cyclic AMP/protein kinase A/CREB system (Daw, 2004). The greater activity of these factors is probably what makes the visual cortex most capable of plasticity at this time. Abolition of any one of them with pharmacological antagonists or genetic knockouts, as well as of glutamic acid decarboxylase 65, brain-derived neurotrophic factor, in some cases alpha-calcium/calmodulin kinase II, and extracellular signal-related kinase abolishes plasticity during the critical period.
There are also factors that increase towards the end of the critical period, perhaps helping to bring it to an end. These include myelination (McGee et al., 2005), and condensation of chondroitin sulfate proteoglycans around the soma and dendrites of the cell (Berardi et al., 2004). Degradation of these proteoglycans and mutants of the myelin protein NoGo both allow the critical period to be extended. Moreover, environmental enrichment (Sale et al., 2007) and adminstration of the antidepressant fluoxetine (Maya Vetencourt et al., 2008) also allow increased plasticity, probably by decreasing intracortical inhibition, and so does rearing in the dark (He et al., 2007). Some of these results may eventually be useful for treating the amblyopia that results from strabismus and anisometropia.
How all these factors fit into a complete picture of what causes the visual cortex to be plastic during the critical period remains to be seen. It is clear that electrical activity impinging on the cortical cells has an eventual effect of the retraction of the axons and dendrites in the deprived pathways, and an expansion of those in the non-deprived pathway. The process occurs through receptors, second messengers, genes and protein synthesis. Any interruption of the activating pathway can abolish plasticity. Then some anatomical changes, lack of one or more factors in the activating pathway, and possibly lack of physiological mechanisms, occur to prevent further plasticity. It is the discovery of factors in the latter process that are most exciting in terms of their potential to extend the critical period and possibly provide a future therapy for the amelioration of amblyopia.
- Berardi, N., T. Pizzorusso, et al. (2004). "Extracellular matrix and visual cortical plasticity: freeing the synapse." Neuron. 44: 905-908.
- Blakemore, C. and R. C. Van Sluyters (1974). "Reversal of the physiological effects of monocular deprivation in kittens: further evidence for a sensitive period." Journal of Physiology 237: 195-216.
- Daw, N. W. (1994). "Mechanisms of plasticity in the visual cortex." Investigative Ophthalmology 35: 4168-4179.
- Daw, N. W. (2003). Critical Periods in the Visual System, chapter 3 in Neurobiology of Infant Vision, ed. Hopkins, B. and Johnson, S. P.. Westport, Praeger.
- Daw, N. W. (2004). Mechanisms of plasticity in the visual cortex, chapter 10 in The Visual Neurosciences, ed. Chalupa, L. M. and Werner, J. S.. Cambridge, MIT Press.
- Daw, N. W. and H. J. Wyatt (1976). "Kittens reared in a unidirectional environment: evidence for a critical period." Journal of Physiology 257: 155-170.
- He, H. Y., B. Ray, et al. (2007). "Experience-dependent recovery of vision following chronic deprivation amblyopia." Nat Neurosci 10(9): 1134-6.
- Hubel, D. H. and T. N. Wiesel (1970). "The period of susceptibility to the physiological effects of unilateral eye closure in kittens." Journal of Physiology 206: 419-436.
- Katz, L. C. and J. C. Crowley (2002). "Development of cortical circuits: lessons from ocular dominance columns." NNSR 3: 34-42.
- LeVay, S., T. N. Wiesel, et al. (1980). "The development of ocular dominance columns in normal and visually deprived monkeys." Journal of Comparative Neurology 191: 1-51.
- Maya Vetencourt, J. F., A. Sale, et al. (2008). "The antidepressant fluoxetine restores plasticity in the adult visual cortex." Science 320(5874): 385-8.
- McGee, A. W., Y. Yang, et al. (2005). "Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor." Science. 309: 2222-2226.
- Mower, G. D. (1991). "The effect of dark rearing on the time course of the critical period in cat visual cortex." Developmental Brain Research 58: 151-158.
- Sacks, O. (2006). "Stereo Sue." New Yorker 82(18): 64.
- Sale, A., J. F. Maya Vetencourt, et al. (2007). "Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition." Nat Neurosci 10(6): 679-81.
- Spalding, D. (1873). "Instinct, with original observations on young animals." MacMillan's magazine 27: 282-293.
- Vaegan and D. Taylor (1979). "Critical period for deprivation amblyopia in children." Transactions of the Ophthalmological Society (UK) 99: 432-439.
- Wick, B., M. Wingard, et al. (1992). "Anisometropic amblyopia: is the patient ever too old to treat?" Optometry and Vision Science 69: 866-878.
- Werker, J. F., J. H. Gilbert, et al. (1981). "Developmental aspects of cross-language speech perception." Child Dev 52(1): 349-55.
- White, L. E. and D. Fitzpatrick (2007). "Vision and cortical map development." Neuron 56(2): 327-38.
- Wiesel, T. N. and D. H. Hubel (1963). "Single cell responses in striate cortex of kittens deprived of vision in one eye." Journal of Neurophysiology 26: 1003-1017.
- Daw, N. W. (2006). Visual Development. New York, Springer.
- Wiesel, T. N. (1982). "Postnatal development of the visual cortex and the influence of environment." Nature. 299: 583-591.