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Critical Period In Brain Development and Childhood Learning

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Key Takeaways

• Critical period is an ethological term that refers to a fixed and crucial time during the early development of an organism when it can learn things that are essential to survival. These influences impact the development of processes such as hearing and vision, social bonding, and language learning.
• The term is most often experienced in the study of imprinting, where it is thought that young birds could only develop an attachment to the mother during a fixed time soon after hatching.
• Neurologically, critical periods are marked by high levels of plasticity in the brain before neural connections become more solidified and stable. In particular, critical periods tend to end when synapses that inhibit the neurotransmitter GABA mature.
• In contrast to critical periods, sensitive periods, otherwise known as “weak critical periods,” happen when an organism is more sensitive than usual to outside factors influencing behavior, but this influence is not necessarily restricted to the sensitive period.
• Scholars have debated the extent to which older organisms can develop certain skills, such as natively-accented foreign languages, after the critical period.

The critical period is a biologically determined stage of development where an organism is optimally ready to acquire some pattern of behavior that is part of typical development. This period, by definition, will not recur at a later stage.

If an organism does not receive exposure to the appropriate stimulus needed to learn a skill during a critical period, it may be difficult or even impossible for that organism to develop certain functions associated with that skill later in life.

This happens because a range of functional and structural elements prevent passive experiences from eliciting significant changes in the brain (Cisneros-Franco et al., 2020).

The first strong proponent of the theory of critical periods was Charles Stockhard (1921), a biologist who attempted to experiment with the effects of various chemicals on the development of fish embryos, though he gave credit to Dareste for originating the idea 30 years earlier (Scott, 1962).

Stockhard’s experiments showed that applying almost any chemical to fish embryos at a certain stage of development would result in one-eyed fish.

These experiments established that the most rapidly growing tissues in an embryo are the most sensitive to any change in conditions, leading to effects later in development (Scott, 1962).

Meanwhile, psychologist Sigmund Freud attempted to explain the origins of neurosis in human patients as the result of early experiences, implying that infants are particularly sensitive to influences at certain points in their lives.

Lorenz (1935) later emphasized the importance of critical periods in the formation of primary social bonds (otherwise known as imprinting) in birds, remarking that this psychological imprinting was similar to critical periods in the development of the embryo.

Soon thereafter, McGraw (1946) pointed out the existence of critical periods for the optimal learning of motor skills in human infants (Scott, 1962).

Example: Infant-Parent Attachment

The concept of critical or sensitive periods can also be found in the domain of social development, for example, in the formation of the infant-parent attachment relationship (Salkind, 2005).

Attachment describes the strong emotional ties between the infant and caregiver, a reciprocal relationship developing over the first year of the child’s life and particularly during the second six months of the first year.

During this attachment period , the infant’s social behavior becomes increasingly focused on the principal caregivers (Salkind, 2005).

The 20th-century English psychiatrist John Bowlby formulated and presented a comprehensive theory of attachment influenced by evolutionary theory.

Bowlby argued that the infant-parent attachment relationship develops because it is important to the survival of the infant and that the period from six to twenty-four months of age is a critical period of attachment.

This coincides with an infant’s increasing tendency to approach familiar caregivers and to be wary of unfamiliar adults. After this critical period, it is still possible for a first attachment relationship to develop, albeit with greater difficulty (Salkind, 2005).

This has brought into question, in a similar vein to language development, whether there is actually a critical development period for infant-caregiver attachment.

Sources debating this issue typically include cases of infants who did not experience consistent caregiving due to being raised in institutions prior to adoption (Salkind, 2005).

Early research into the critical period of attachment, published in the 1940s, reports consistently that children raised in orphanages subsequently showed unusual and maladaptive patterns of social behavior, difficulty in forming close relationships, and being indiscriminately friendly toward unfamiliar adults (Salkind, 2005).

Later, research from the 1990s indicated that adoptees were actually still able to form attachment relationships after the first year of life and also made developmental progress following adoption.

Nonetheless, these children had an overall increased risk of insecure or maladaptive attachment relationships with their adoptive parents. This evidence supports the notion of a sensitive period, but not a critical period, in the development of first attachment relationships (Salkind, 2005).

Mechanisms for Critical Periods

Both genetics and sensory experiences from outside the body shape the brain as it develops (Knudsen, 2004). However, the developmental stage that an organism is in significantly impacts how much the brain can change based on these experiences.

In scientific terms, the brain’s plasticity changes over the course of a lifespan. The brain is very plastic in the early stages of life before many key connections take root, but less so later.

This is why researchers have shown that early experience is crucial for the development of, say, language and musical abilities, and these skills are more challenging to take up in adulthood (Skoe and Kraus, 2013; White et al., 2013; Hartshorne et al., 2018).

As brains mature, the connections in them become more fixed. The brain’s transitions from a more plastic to a more fixed state advantageously allow it to retain new and complex processes, such as perceptual, motor, and cognitive functions (Piaget, 1962).

Children’s gestures, for example, pride and predict how they will acquire oral language skills (Colonnesi et al., 2010), which in turn are important for developing executive functions (Marcovitch and Zelazo, 2009).

However, this formation of stable connections in the brain can limit how the brain’s neural circuitry can be revised in the future. For example, if a young organism has abnormal sensory experiences during the critical period – such as auditory or visual deprivation – the brain may not wire itself in a way that processes future sensory inputs properly (Gallagher et al., 2020).

One illustration of this is the timing of cochlear implants – a prosthesis that restores hearing in some deaf people. Children who receive cochlear implants before two years of age are more likely to benefit from them than those who are implanted later in life (Kral and Eggermont, 2007; Gallagher et al., 2020).

Similarly, the visual deprivation caused by cataracts in infants can cause similar consequences. When cataracts are removed during early infancy, individuals can develop relatively normal vision; however, when the cataracts are not removed until adulthood, this results in substantially poorer vision (Martins Rosa et al., 2013).

After the critical period closes, abnormal sensory experiences have a less drastic effect on the brain and lead to – barring direct damage to the central nervous system – reversible changes (Gallagher et al., 2020). Much of what scientists know about critical periods derives from animal studies , as these allow researchers greater control over the variables that they are testing.

This research has found that different sensory systems, such as vision, auditory processing, and spatial hearing, have different critical periods (Gallagher et al., 2020).

The brain regulates when critical periods open and close by regulating how much the brain’s synapses take up neurotransmitters , which are chemical substances that affect the transmission of electrical signals between neurons.

In particular, over time, synapses decrease their uptake of gamma-aminobutyric acid, better known as GABA. At the beginning of the critical period, outside sources become more effective at influencing changes and growth in the brain.

Meanwhile, as the inhibitory circuits of the brain mature, the mature brain becomes less sensitive to sensory experiences (Gallagher et al., 2020).

Critical Periods vs Sensitive Periods

Critical periods are similar to sensitive periods, and scholars have, at times, used them interchangeably. However, they describe distinct but overlapping developmental processes.

A sensitive period is a developmental stage where sensory experiences have a greater impact on behavioral and brain development than usual; however, this influence is not exclusive to this time period (Knudsen, 2004; Gallagher, 2020). These sensitive periods are important for skills such as learning a language or instrument.

In contrast, A critical period is a special type of sensitive period – a window where sensory experience is necessary to shape the neural circuits involved in basic sensory processing, and when this window opens and closes is well-defined (Gallagher, 2020).

Researchers also refer to sensitive periods as weak critical periods. Some examples of strong critical periods include the development of vision and hearing, while weak critical periods include phenome tuning – how children learn how to organize sounds in a language, grammar processing, vocabulary acquisition, musical training, and sports training (Gallagher et al., 2020).

Critical Period Hypothesis

One of the most notable applications of the concept of a critical period is in linguistics. Scholars usually trace the origins of the debate around age in language acquisition to Penfield and Robert’s (2014) book Speech and Brain Mechanisms.

In the 1950s and 1960s, Penfield was a staunch advocate of early immersion education (Kroll and De Groot, 2009). Nonetheless, it was Lenneberg, in his book Biological Foundations of Language, who coined the term critical period (1967) in describing the language period.

Lennenberg (1967) described a critical period as a period of automatic acquisition from mere exposure” that “seems to disappear after this age.” Scovel (1969) later summarized and narrowed Penfield’s and Lenneberg’s view on the critical period hypothesis into three main claims:

• Adult native speakers can identify non-natives by their accents immediately and accurately.
• The loss of brain plasticity at about the age of puberty accounts for the emergence of foreign accents./li>
• The critical period hypothesis only holds for speech (whether or not someone has a native accent) and does not affect other areas of linguistic competence.

Linguists have since attempted to find evidence for whether or not scientific evidence actually supports the critical period hypothesis, if there is a critical period for acquiring accentless speech, for “morphosyntactic” competence, and if these are true, how age-related differences can be explained on the neurological level (Scovel, 2000).

The critical period hypothesis applies to both first and second-language learning. Until recently, research around the critical period’s role in first language acquisition revolved around findings about so-called “feral” children who had failed to acquire language at an older age after having been deprived of normal input during the critical period.

However, these case studies did not account for the extent to which social deprivation, and possibly food deprivation or sensory deprivation, may have confounded with language input deprivation (Kroll and De Groot, 2009).

More recently, researchers have focused more systematically on deaf children born to hearing parents who are therefore deprived of language input until at least elementary school.

These studies have found the effects of lack of language input without extreme social deprivation: the older the age of exposure to sign language is, the worse its ultimate attainment (Emmorey, Bellugi, Friederici, and Horn, 1995; Kroll and De Groot, 2009).

However, Kroll and De Groot argue that the critical period hypothesis does not apply to the rate of acquisition of language. Adults and adolescents can learn languages at the same rate or even faster than children in their initial stage of acquisition (Slavoff and Johnson, 1995).

However, adults tend to have a more limited ultimate attainment of language ability (Kroll and De Groot, 2009).

There has been a long lineage of empirical findings around the age of acquisition. The most fundamental of this research comes from a series of studies since the late 1970s documenting a negative correlation between age of acquisition and ultimate language mastery (Kroll and De Grott, 2009).

Nonetheless, different periods correspond to sensitivity to different aspects of language. For example, shortly after birth, infants can perceive and discriminate speech sounds from any language, including ones they have not been exposed to (Eimas et al., 1971; Gallagher et al., 2020).

Around six months of age, exposure to the primary language in the infant’s environment guides phonetic representations of language and, subsequently, the neural representations of speech sounds of the native language while weakening those of unused sounds (McClelland et al., 1999; Gallagher et al., 2020).

Vocabulary learning experiences rapid growth at about 18 months of age (Kuhl, 2010).

Critical Evaluation

More than any other area of applied linguistics, the critical period hypothesis has impacted how teachers teach languages. Consequently, researchers have critiqued how important the critical period is to language learning.

For example, several studies in early language acquisition research showed that children were not necessarily superior to older learners in acquiring a second language, even in the area of pronunciation (Olson and Samuels, 1973; Snow and Hoefnagel-Hohle, 1978; Scovel, 2000).

In fact, the majority of researchers at the time appeared to be skeptical about the existence of a critical period, with some explicitly denying its existence.

Counter to one of the primary tenets of Scovel’s (1969) critical period hypothesis, there have been several cases of people who have acquired a second language in adulthood speaking with native accents.

For example, Moyer’s study of highly proficient English-speaking learners of German suggested that at least one of the participants was judged to have native-like pronunciation in his second language (1999), and several participants in Bongaerts (1999) study of highly proficient Dutch speakers of French spoke with accents judged to be native (Scovel, 2000).

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What Is the Critical Period Hypothesis?

The critical period hypothesis is a theory in the study of language acquisition which posits that there is a critical period of time in which the human mind can most easily acquire language. This idea is often considered with regard to primary language acquisition, and those who agree with this hypothesis argue that language must be learned in the first few years of life or else the ability to acquire language is greatly hindered. The critical period hypothesis is also used in secondary language acquisition, regarding the idea of a time period in which a secondary language can be most easily acquired.

With regard to primary language acquisition, which refers to the process by which a person learns his or her first language , the critical period hypothesis is quite dramatic. This idea indicates that a person has only a set period of time in which he or she can learn a first language, usually the first three to ten years of development. During this time, language can be learned and acquired through exposure to language; simply hearing others talking on an ongoing and regular basis is sufficient. Once this time period is over, however, those who agree with the critical period hypothesis argue that primary language acquisition may be impossible or greatly impaired.

There is a great deal of research into human brain development that supports this hypothesis, but it is still difficult to prove. One of the only conclusive ways to prove this hypothesis would be to have a person isolated from infancy until about the age of ten, without exposure to human speech. Such upbringing would be unthinkable, however, so this type of experiment cannot be conducted and the hypothesis remains largely unproven.

Unfortunate situations in which a child has been abused and isolated by his or her caregivers have provided opportunities to support the critical period hypothesis. In at least one instance, medical care and study of the child did demonstrate that full language acquisition was nearly impossible. Though this occurrence did support the hypothesis, secondary factors such as possible brain damage make the evidence flawed.

The critical period hypothesis is also frequently applied to secondary language acquisition, though in a somewhat less dramatic way. With regard to secondary language, many linguists and speech therapists agree that a second language can be acquired more easily when someone is young. Studies of the brain indicate that in youth the brain is still developing more quickly and new linguistic information can be processed and incorporated into the brain more easily. Once this period is over, however, secondary language acquisition is still certainly possible, though it can be more difficult.

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Critical Period

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• Yan Wang 3 &
• Jing Guo 3  

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Crucial time ; Sensitive period

A maturational stage during the lifespan of an organism in which the organism’s nervous system is especially sensitive to certain environmental stimuli. The organism is more sensitive to environmental stimulation during a critical period than at other times during its life.

Introduction

The phenomenon of critical period was first described by William James ( 1899 ) as “the transitoriness of instincts.” The term “critical period” was proposed by the Austrian ecologist based on his observations that newly hatched poultries, such as chicks and geese, would follow the object, usually their mother, if exposed to within a certain short time after birth.

According to Lorenz, if the young animal was not exposed to the particular stimulus during the “critical period” to learn a given skill or trait, it would become extremely struggling to develop particular behavioral pattern in the later life.

A vast of existing literature has identified the...

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Cognitive scientists define critical period for learning language

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A great deal of evidence suggests that it is more difficult to learn a new language as an adult than as a child, which has led scientists to propose that there is a “critical period” for language learning. However, the length of this period and its underlying causes remain unknown.

A new study performed at MIT suggests that children remain very skilled at learning the grammar of a new language much longer than expected — up to the age of 17 or 18. However, the study also found that it is nearly impossible for people to achieve proficiency similar to that of a native speaker unless they start learning a language by the age of 10.

“If you want to have native-like knowledge of English grammar you should start by about 10 years old. We don’t see very much difference between people who start at birth and people who start at 10, but we start seeing a decline after that,” says Joshua Hartshorne, an assistant professor of psychology at Boston College, who conducted this study as a postdoc at MIT.

People who start learning a language between 10 and 18 will still learn quickly, but since they have a shorter window before their learning ability declines, they do not achieve the proficiency of native speakers, the researchers found. The findings are based on an analysis of a grammar quiz taken by nearly 670,000 people, which is by far the largest dataset that anyone has assembled for a study of language-learning ability.

“It’s been very difficult until now to get all the data you would need to answer this question of how long the critical period lasts,” says Josh Tenenbaum, an MIT professor of brain and cognitive sciences and an author of the paper. “This is one of those rare opportunities in science where we could work on a question that is very old, that many smart people have thought about and written about, and take a new perspective and see something that maybe other people haven’t.”

Steven Pinker, a professor of psychology at Harvard University, is also an author of the paper, which appears in the journal Cognition on May 1.

Quick learners

While it’s typical for children to pick up languages more easily than adults — a phenomenon often seen in families that immigrate to a new country — this trend has been difficult to study in a laboratory setting. Researchers who brought adults and children into a lab, taught them some new elements of language, and then tested them, found that adults were actually better at learning under those conditions. Such studies likely do not accurately replicate the process of long-term learning, Hartshorne says.

“Whatever it is that results in what we see in day-to-day life with adults having difficulty in fully acquiring the language, it happens over a really long timescale,” he says.

Following people as they learn a language over many years is difficult and time-consuming, so the researchers came up with a different approach. They decided to take snapshots of hundreds of thousands of people who were in different stages of learning English. By measuring the grammatical ability of many people of different ages, who started learning English at different points in their life, they could get enough data to come to some meaningful conclusions.

Hartshorne’s original estimate was that they needed at least half a million participants — unprecedented for this type of study. Faced with the challenge of attracting so many test subjects, he set out to create a grammar quiz that would be entertaining enough to go viral.

With the help of some MIT undergraduates, Hartshorne scoured scientific papers on language learning to discover the grammatical rules most likely to trip up a non-native speaker. He wrote questions that would reveal these errors, such as determining whether a sentence such as “Yesterday John wanted to won the race” is grammatically correct. 

To entice more people to take the test, he also included questions that were not necessary for measuring language learning, but were designed to reveal which dialect of English the test-taker speaks. For example, an English speaker from Canada might find the sentence “I’m done dinner” correct, while most others would not.

Within hours after being posted on Facebook, the 10-minute quiz “ Which English? ” had gone viral.

“The next few weeks were spent keeping the website running, because the amount of traffic we were getting was just overwhelming,” Hartshorne says. “That’s how I knew the experiment was sufficiently fun.”

A long critical period

After taking the quiz, users were asked to reveal their current age and the age at which they began learning English, as well as other information about their language background. The researchers ended up with complete data for 669,498 people, and once they had this huge amount of data, they had to figure out how to analyze it.

“We had to tease apart how many years has someone been studying this language, when they started speaking it, and what kind of exposure have they been getting: Were they learning in a class or were they immigrants to an English-speaking country?” Hartshorne says.

The researchers developed and tested a variety of computational models to see which was most consistent with their results, and found that the best explanation for their data is that grammar-learning ability remains strong until age 17 or 18, at which point it drops. The findings suggest that the critical period for learning language is much longer than cognitive scientists had previously thought.

“It was surprising to us,” Hartshorne says. “The debate had been over whether it declines from birth, starts declining at 5 years old, or starts declining starting at puberty.”

The authors note that adults are still good at learning foreign languages, but they will not be able to reach the level of a native speaker if they begin learning as a teenager or as an adult.

"Although it has long been observed that learning a second language is easier early in life, this study provides the most compelling evidence to date that there is a specific time in life after which the ability to learn the grammar of a new language declines," says Mahesh Srinivasan, an assistant professor of psychology at the University of California at Berkeley, who was not involved in the study. “This is a major step forward for the field. The study also opens surprising, new questions, because it suggests that the critical period closes much later than previously thought."

Still unknown is what causes the critical period to end around age 18. The researchers suggest that cultural factors may play a role, but there may also be changes in brain plasticity that occur around that age.

“It’s possible that there’s a biological change. It’s also possible that it’s something social or cultural,” Tenenbaum says. “There’s roughly a period of being a minor that goes up to about age 17 or 18 in many societies. After that, you leave your home, maybe you work full time, or you become a specialized university student. All of those might impact your learning rate for any language.”

Hartshorne now plans to run some related studies in his lab at Boston College, including one that will compare native and non-native speakers of Spanish. He also plans to study whether individual aspects of grammar have different critical periods, and whether other elements of language skill such as accent have a shorter critical period.

The researchers also hope that other scientists will make use of their data, which they have posted online , for additional studies.

“There are lots of other things going on in this data that somebody could analyze,” Hartshorne says. “We do want to draw other scientists’ attention to the fact that the data is out there and they can use it.”

The research was funded by the National Institutes of Health and MIT’s Center for Minds, Brains, and Machines.

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Press mentions, scientific american.

Bucking conventional wisdom, research co-authored by Prof. Josh Tenenbaum shows that “picking up the subtleties of grammar in a a second language does not fade until well into the teens,” writes Dana G. Smith for Scientific American . “To become completely fluent, however, learning should start before the age of 10.”

New research suggests “children are highly skilled at learning the grammar of a new language up until the age of 17 or 18, much longer than previously thought,” reports Kashmira Gander in Newsweek. “We may need to go back to the drawing board in trying to explain why adults have trouble learning language,” Joshua Hartshorne, who co-wrote the study as a postdoc at MIT, tells Gander.

A study co-authored by Prof. Josh Tenenbaum finds that learning a new language should start before age 10 to achieve a native-like grasp of the grammar, reports BBC News . People remain highly skilled language learners until about 17 or 18, but then fall off, which Tenenbaum says could be due to “a biological change” or “something social or cultural.”

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Age and the critical period hypothesis

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Christian Abello-Contesse, Age and the critical period hypothesis, ELT Journal , Volume 63, Issue 2, April 2009, Pages 170–172, https://doi.org/10.1093/elt/ccn072

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In the field of second language acquisition (SLA), how specific aspects of learning a non-native language (L2) may be affected by when the process begins is referred to as the ‘age factor’. Because of the way age intersects with a range of social, affective, educational, and experiential variables, clarifying its relationship with learning rate and/or success is a major challenge.

There is a popular belief that children as L2 learners are ‘superior’ to adults ( Scovel 2000 ), that is, the younger the learner, the quicker the learning process and the better the outcomes. Nevertheless, a closer examination of the ways in which age combines with other variables reveals a more complex picture, with both favourable and unfavourable age-related differences being associated with early- and late-starting L2 learners ( Johnstone 2002 ).

The ‘critical period hypothesis’ (CPH) is a particularly relevant case in point. This is the claim that there is, indeed, an optimal period for language acquisition, ending at puberty. However, in its original formulation ( Lenneberg 1967 ), evidence for its existence was based on the relearning of impaired L1 skills, rather than the learning of a second language under normal circumstances.

Furthermore, although the age factor is an uncontroversial research variable extending from birth to death ( Cook 1995 ), and the CPH is a narrowly focused proposal subject to recurrent debate, ironically, it is the latter that tends to dominate SLA discussions ( García Lecumberri and Gallardo 2003 ), resulting in a number of competing conceptualizations. Thus, in the current literature on the subject ( Bialystok 1997 ; Richards and Schmidt 2002 ; Abello-Contesse et al. 2006), references can be found to (i) multiple critical periods (each based on a specific language component, such as age six for L2 phonology), (ii) the non-existence of one or more critical periods for L2 versus L1 acquisition, (iii) a ‘sensitive’ yet not ‘critical’ period, and (iv) a gradual and continual decline from childhood to adulthood.

It therefore needs to be recognized that there is a marked contrast between the CPH as an issue of continuing dispute in SLA, on the one hand, and, on the other, the popular view that it is an invariable ‘law’, equally applicable to any L2 acquisition context or situation. In fact, research indicates that age effects of all kinds depend largely on the actual opportunities for learning which are available within overall contexts of L2 acquisition and particular learning situations, notably the extent to which initial exposure is substantial and sustained ( Lightbown 2000 ).

Thus, most classroom-based studies have shown not only a lack of direct correlation between an earlier start and more successful/rapid L2 development but also a strong tendency for older children and teenagers to be more efficient learners. For example, in research conducted in the context of conventional school programmes, Cenoz (2003) and Muñoz (2006) have shown that learners whose exposure to the L2 began at age 11 consistently displayed higher levels of proficiency than those for whom it began at 4 or 8. Furthermore, comparable limitations have been reported for young learners in school settings involving innovative, immersion-type programmes, where exposure to the target language is significantly increased through subject-matter teaching in the L2 ( Genesee 1992 ; Abello-Contesse 2006 ). In sum, as Harley and Wang (1997) have argued, more mature learners are usually capable of making faster initial progress in acquiring the grammatical and lexical components of an L2 due to their higher level of cognitive development and greater analytical abilities.

In terms of language pedagogy, it can therefore be concluded that (i) there is no single ‘magic’ age for L2 learning, (ii) both older and younger learners are able to achieve advanced levels of proficiency in an L2, and (iii) the general and specific characteristics of the learning environment are also likely to be variables of equal or greater importance.

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What are the main arguments for and against the critical period hypothesis, and what are alternative explanations?

Why is the critical period hypothesis so heavily disputed, yet widely accepted; what are its major strengths and weaknesses; what other explanations exist for the perceived "critical period", if it does not exist?

• critical-period

Let us start with a simple, relatively informal statement: “in most cases, those who start learning a language as children become ultimately become more proficient in a language than those who start learning it later”. This is uncontroversial, and something I think the vast majority of second-language acquisition researchers would agree on. However, this is not how the Critical Period Hypothesis (CPH) is understood within the field of Second Language Acquisition (SLA). CPH is a large subject, and your question is hard to answer in a few paragraphs. Therefore, I am reusing large fragments of an assignment I wrote on this very topic for an SLA course a few years ago. Let me know if something is unclear or the style is too terse at some points.

Summary (TL;DR)

There is no universally accepted definition of a critical period within linguistics and some of the controversies are caused by the fact that different researchers use different definitions.

There are a few key findings that are not controversial:

• early learners perform consistently well in all aspects of language use,
• as we move the starting age, they perform statistically worse and worse until puberty,
• however, the decrease in performance is not uniform.

An explanation, provided by Bialystok (1997) as an alternative to CPH, is the different learning style of children, compared to late learners.

Paradoxically, the differences (or lack thereof) between those who learn a foreign language as adults is the key factor in deciding whether CPH is true or not, and a controversial one:

• Some studies found correlations between the age adult learners started learning a language and their ultimate attainment. In other words, these studies suggest that if we compare people who have been learning a language for a very long time, the ultimate attainment of those who started at the age of 20 is statistically higher than the ultimate attainment of those who started at the age of 40. These studies argue that there is no CPH in the childhood, but rather that our abilities in learning a new language consistently decrease throughout our whole lives.
• Other studies found no clear correlations between the starting age and the ultimate attainment among adult language learners. They point out that the correlation between the starting age and ultimate attainment is clear for those who started before puberty. Based on that, they argue that there is something qualitatively different about starting to learn in an early age, and therefore conclude that it is an argument for CPH.

Definitions of the critical period used by those who argue against CPH

Controversies with the Critical Period Hypothesis (CPH) are related to the issue of ultimate attainment of early and late language learners, that is, the highest language proficiency level they can attain. The patterns in ultimate attainment may be explained by CPH, but they may also have different explanations. Some researchers support some form of the Critical Period Hypothesis (Johnson and Newport 1989, DeKeyser and Larson-Hall 2005, Patkowsky 1994, Scovel 1988), while others argue against it (Bialystok 1997).

A major problem with the Critical Period Hypothesis is that there appears to be no universally accepted definition of a critical period within linguistics . Bialystok (1997) bases her discussion of the critical/sensitive period (which she takes to be synonymous 1 ) on a specific technical definition used in ethology, which includes 14 essential structural characteristics that describe such a period (Bornstein 1989). She argues that one of these characteristics is especially problematic – the system: “structure or function altered in the sensitive period” (Bornstein 1989:184). In other words, she argues that there is no period where a structure in the brain is modified in a way that makes subsequent language learning harder or impossible. Bialystok does, however, agree that there is an optimal period for language learning – something that can be characterised by the statement “ On average, children are more successful than adults when faced with the task of learning a second language ” (Bialystok 1997:117). Despite the controversy around other issues, this fact is uncontested and has been verified by numerous studies .

Bialystok (1997) rejects the existence of a critical period, because of lack of postulated structure that is modified when the period is over. She postulates that an important factor that causes differences in ultimate attainment between early and late starters is learning style: children prefer accommodation (creating new concepts) over assimilation (extending existing concepts). The question remains: why do they prefer accommodation? She suggests that “[t]his may be because children are in the process of creating new categories all the time as they are learning new information” (Bialystok 1997:132).

Definitions of the critical period used by supporters of CPH

The researchers who support some form of the Critical Period Hypothesis (Johnson and Newport 1989, DeKeyser and Larson-Hall 2005), formulate it in a form that is much weaker than Bialystok's (1997) formulation. What they postulate often resembles what Bialystok calls the optimal age.

Johnson and Newport (1989) reformulated CPH into two alternative hypotheses, in order to fit second language acquisition into the picture:

The exercise hypothesis : “Early in life, humans have a superior capacity for acquiring languages. If the capacity is not exercised during this time, it will disappear or decline with maturation. If the capacity is exercised, however, further language learning abilities will remain intact throughout life.” (Johnson and Newport 1989:64)

The maturational state hypothesis : “Early in life, humans have a superior capacity for acquiring languages. This capacity disappears or declines with maturation.” (Johnson and Newport 1989:64)

We can see that if a critical period was found for second language acquisition, we could be almost sure that it exists for L1 acquisition as well (the maturational state hypothesis). However, we cannot deduce in this way in case of the exercise hypothesis – non-existence of a critical period for L2 acquisition does not exclude in any way a possibility of such period for the first language (Bialystok 1997).

DeKeyser and Larson-Hall (2005) formulate the hypothesis as: “language acquisition from mere exposure (i.e. implicit learning) […] is severely limited in older adolescents and adults”. Their formulation is quite vague, as is the constatation that there is a “qualitative change in language learning capacities somewhere between 4 and 18 years”.

There are also definitions that restrict the Critical Period Hypothesis to specific subareas of the language faculty. The most commonly mentioned area is phonology, see e.g. Patkowsky (1994, cited in Bialystok 1997), Scovel (1988, cited in Bialystok 1997).

Age effects before and after puberty

The current consensus is that early learners perform consistently well in all aspects of language use. As we move the starting age, they perform statistically worse and worse until puberty. The decrease in performance is not uniform, and in some areas (such as phonology) it is particularly visible. Performance on the same level as early bilinguals is possible, but rare.

Probably the most controversial aspect is the performance of adult learners. After puberty there is much bigger variance in the performance, so data are more prone to different interpretations. The results obtained by Derwing and Munro (2013) suggest that comprehensibility and good accent are negatively correlated with the age of arrival, that is, the age when English language immersion started. Johnson and Newport (1989) found no correlation of starting age after puberty with ultimate language proficiency, while Bialystok (1997) re-analysed these data and found some negative correlation. A meta-analysis by DeKeyser and Larson-Hall (2005) downplays the role of post-adolescent correlations. As we can see, the jury is still out on this debate.

1 In neuroscience critical period and sensitive period are two separate concepts, see Knudsen (2004).

Bibliography

• Bialystok, E. 1997. The structure of age: in search of barriers to second language acquisition. Second Language Research 13(2): 116-137.
• Bornstein, M.H. 1989. Sensitive periods in development: structural characteristics and causal interpretations. Psychological Bulletin 105,179–97.
• DeKeyser, R. and J. Larson-Hall. 2005. What does the critical period really mean? In J. F. Kroll and A. M. B. de Groot. 2005. Handbook of bilingualism: Psycholinguistic approaches . Cary, NC: Oxford University Press. Pp. 109–27.
• Derwing, T. M., & Munro, M. J. 2013. The development of L2 oral language skills in two L1 groups: A 7-year study. Language Learning 63, 163-185.
• Johnson, J.S., & Newport, E.L. 1989. Critical period effects in second language learning: The influence of maturational state on the acquisition of English as a second language. Cognitive Psychology , 21, 60-99.
• Knudsen, E. I. 2004. Sensitive periods in the development of the brain and behavior. Journal of Cognitive Neuroscience , 16, 1412-25
• Newport, E. L., & Supalla, T. 1987. A critical period effect in the acquisition of a primary language .
• Patkowsky, M. 1980. The sensitive period for the acquisition of syntax in a second language. Language Learning 30, 449–72
• Scovel, T. 1988. A time to speak: a psycholinguistic inquiry into the critical period for human speech . New York: Newbury House

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Critical Period in Psychology

Table of Contents

What are Critical Periods

A critical period is a phase during which the brain cell connections are more plastic and receptive to the influence of a certain kind of life experience. These connections, called synapses, can form or strengthen more easily during this period of time. Synaptic connections usually mature and stabilize after this time period, making the wirings harder to change at a later age. Lacking certain experiences in the early years of life can have a profound effect on developing neural connections.

Critical Period Hypothesis

According to the Critical Period Hypothesis, during the critical period, new skills or traits can be formed given the proper life experience. If the necessary experience is not available during this time, it becomes much harder, less successful, or even impossible to acquire the skill or trait after the window of opportunity closes.

This is proven true in sensory systems in humans and animals, such as the development of the visual system.

In animal studies, if one eye (but not both) is covered right after birth, the deprived eye will lose visual acuity permanently, even if the covered period is brief postnatal. This is because sensory deprivation and the lack of visual input during that time can cause structural changes in the brain.

Critical vs Sensitive Period

The main difference between a critical period and a sensitive period is that the critical period is a limited time frame during which certain development can occur, while the sensitive period is a window of time where development is more easily achieved.

A sensitive period is similar to a critical period in which neural circuits are relatively more plastic and more sensitive to the influence of experience. However, new synapses can still form for an extended period of time outside of the sensitive period despite being harder.

Some scientists refer to these as weak critical periods.

Why Is Critical Period Important

Critical periods are important because many crucial functions of our body are established during a specific time, and some only during those periods.

Research findings have found that the following functions are best developed during their critical periods.

Emotional regulation

Self regulation in children is the ability to monitor and modulate emotions. Learning to self-regulate is a key milestone in a child’s early development. It can significantly impact a child’s relationships, academic performance, mental health, and well-being in the long term.

In human studies conducted in a Romanian orphanage, only orphans who were adopted by foster families before the age of 2 were able to develop emotional regulation skills comparable to those of the never institutionalized children. Those who remained in the orphanage suffered from deprivation of social contact or maternal care. Social impairments and the lack of emotional regulation skills were evident.

The sensitive period of emotional self-regulation is therefore believed to be from birth to age 2.

Vision System

There are different critical periods for different visual functions. They usually fall between birth and puberty.

Early research shows that visual acuity develops from birth to around age 5 and the period between ages 3 and 5 shows the most growth.

Stereopsis, the perception of depth, has a critical period that ends at 2 years of age.

Susceptibility to damage in visual development also has its own critical period. For instance, amblyopia, the condition where one of the eyes has reduced vision because the eye and brain are not working together properly, can result between several months of age and 7 to 8 years.

Absolute Pitch in Music Listening

Absolute pitch is the ability to identify and produce the perfect pitch of a musical sound without external sounds as reference points.

Children who started musical training between ages 4 and 6 are most likely to reach the absolute pitch.

But training that occurs after the age of 9 rarely leads to that level of proficiency.

Auditory Processing

For children who are born with congenital deafness, the absence of auditory input from birth can severely affect their ability to learn to speak.

Scientists have found that when cochlear implants are installed to bypass the non-functional inner ears in deaf children before age 3.5, they can most likely learn to speak successfully, especially if they are also exposed to language-rich environments.

Critical Period For Language Acquisition

When applied to language learning, the Critical Period Hypothesis states that there is a critical time during which individuals are more capable of acquiring new languages with native-like proficiency.

The critical period of language development begins in early childhood and concludes shortly before the onset of puberty.

After that period of development, it becomes much more difficult to acquire new language competency and full mastery, even in a linguistically rich environment.

The original hypothesis was first popularized by Eric Lenneberg, a linguist and neurologist, in a landmark book Biological Foundations of Language in 1967.

According to this theory, the process of learning a new language is constrained by a critical period. There is a distinct discontinuity in outcomes between learning within the critical period and learning outside it. The time of that discontinuity reflects the end of the critical period.

However, it is still possible for adults to learn to use a new language beyond puberty. It is just harder and may take longer compared to young children.

Thus, learning perfect phonology and grammar in a second language has a critical period, but learning a foreign language (as general speakers) seems to have more of a sensitive period rather than a critical period (although this alternative definition is still controversial and individual results do vary).

What Parents Should Know

It may feel overwhelming that there are so many different critical periods at different ages in brain development.

Parents who have “missed” some of the critical periods are worried that their children are now destined to fail. Those who have “met” the critical periods successfully are glad that their children are now set for life and their jobs are done.

The truth is that neither of these is true.

The critical period is a controversial science concept because it implies there is a hard cutoff. If the skill is not developed during that time, the opportunity to develop this function will be gone forever.

But some of those skills are actually experience-expectant rather than experience-dependent . Experience-expectant means the stimuli from life experiences are expected in normal development. For instance, language, vision, and hearing are expected experiences practically guaranteed to be available to human infants. Parents rarely have to make an effort to introduce such sensory experiences.

Abilities that depend on the presence of specific experiences are experience-dependent . Parents need to provide the appropriate early life experiences for these skills to develop. Emotional regulation, speech & language , and absolute pitch are experience-dependent examples.

But the good news is many experience-dependent traits have sensitive periods rather than critical periods. Even when early exposure is missing during the optimal time, the skills can still develop. It might just be harder or take longer.

Among the experience-dependent abilities, emotional regulation plays an important role in a child’s growth and future well-being. So the most important thing for parents to do is to provide a nurturing environment for their children and help them build resilience .

Final Thoughts On Critical Period

As parents, it’s better if we make sure our children are not deprived of critical experiences, especially during critical periods. However, it doesn’t mean we should buy the latest “Mozart for babies” DVD or sign our toddlers up for dozes of enrichment classes. What our children need is a nurturing environment and exposure to common life experiences, such as talking, playing, and reading to them.

There is also no need to sweat over missing the optimal times because it’s never too late to start providing good life experiences to our kids.

References for Critical Periods

• 1. Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci . Published online November 2005:877-888. doi:https://doi.org/10.1038/nrn1787
• 2. McLaughlin KA, Sheridan MA, Tibu F, Fox NA, Zeanah CH, Nelson CA III. Causal effects of the early caregiving environment on development of stress response systems in children. Proc Natl Acad Sci USA . Published online April 20, 2015:5637-5642. doi:https://doi.org/10.1073/pnas.1423363112
• 3. Levitin DJ, Rogers SE. Absolute pitch: perception, coding, and controversies. Trends in Cognitive Sciences . Published online January 2005:26-33. doi:https://doi.org/10.1016/j.tics.2004.11.007
• 4. Gervain J, Vines BW, Chen LM, et al. Valproate reopens critical-period learning of absolute pitch. Front Syst Neurosci . Published online 2013. doi:https://doi.org/10.3389/fnsys.2013.00102
• 5. Kral A, Sharma A. Developmental neuroplasticity after cochlear implantation. Trends in Neurosciences . Published online February 2012:111-122. doi:https://doi.org/10.1016/j.tins.2011.09.004
• 6. Hakuta K, Bialystok E, Wiley E. Critical Evidence. Psychol Sci . Published online January 2003:31-38. doi:https://doi.org/10.1111/1467-9280.01415
• 7. Friederici AD, Steinhauer K, Pfeifer E. Brain signatures of artificial language processing: Evidence challenging the critical period hypothesis. Proceedings of the National Academy of Sciences . Published online January 2, 2002:529-534. doi:https://doi.org/10.1073/pnas.012611199
• 8. Birdsong D. Second Language Acquisition and the Critical Period Hypothesis . Routledge; 1999.
• 9. Birdsong D, Molis M. On the Evidence for Maturational Constraints in Second-Language Acquisition. Journal of Memory and Language . Published online February 2001:235-249. doi:https://doi.org/10.1006/jmla.2000.2750

Disclaimer: The content of this article is intended for informational purposes only and should not be considered medical advice. Always consult your healthcare provider for medical concerns.

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The Story of Genie Wiley

What her tragic story revealed about language and development

Who Was Genie Wiley?

Why was the genie wiley case so famous, did genie learn to speak, ethical concerns.

While there have been a number of cases of feral children raised in social isolation with little or no human contact, few have captured public and scientific attention, like that of Genie Wiley.

Genie spent almost her entire childhood locked in a bedroom, isolated, and abused for over a decade. Her case was one of the first to put the critical period theory to the test. Could a child reared in utter deprivation and isolation develop language? Could a nurturing environment make up for a horrifying past?

In order to understand Genie's story, it is important to look at what is known about her early life, the discovery of the abuse she had endured, and the subsequent efforts to treat and study her.

Early Life (1957-1970)

Genie's life prior to her discovery was one of utter deprivation. She spent most of her days tied naked to a potty chair, only able to move her hands and feet. When she made noise, her father would beat her. The rare times her father did interact with her, it was to bark or growl. Genie Wiley's brother, who was five years older than Genie, also suffered abuse under their father.

Discovery and Study (1970-1975)

Genie's story came to light on November 4, 1970, in Los Angeles, California. A social worker discovered the 13-year old girl after her mother sought out services for her own health. The social worker soon discovered that the girl had been confined to a small room, and an investigation by authorities quickly revealed that the child had spent most of her life in this room, often tied to a potty chair.

A Genie Wiley documentary was made in 1997 called "Secrets of the Wild Child." In it, Susan Curtiss, PhD, a linguist and researcher who worked with Genie, explained that the name Genie was used in case files to protect the girl's identity and privacy.

The case name is Genie. This is not the person's real name, but when we think about what a genie is, a genie is a creature that comes out of a bottle or whatever but emerges into human society past childhood. We assume that it really isn't a creature that had a human childhood.

Both parents were charged with abuse , but Genie's father died by suicide the day before he was due to appear in court, leaving behind a note stating that "the world will never understand."

The story of Genie's case soon spread, drawing attention from both the public and the scientific community. The case was important, said psycholinguist and author Harlan Lane, PhD, because "our morality doesn’t allow us to conduct deprivation experiments with human beings; these unfortunate people are all we have to go on."

With so much interest in her case, the question became what should be done to help her. A team of psychologists and language experts began the process of rehabilitating Genie.

The National Institute of Mental Health (NIMH) provided funding for scientific research on Genie’s case. Psychologist David Rigler, PhD, was part of the "Genie team" and he explained the process.

I think everybody who came in contact with her was attracted to her. She had a quality of somehow connecting with people, which developed more and more but was present, really, from the start. She had a way of reaching out without saying anything, but just somehow by the kind of look in her eyes, and people wanted to do things for her.

Genie's rehabilitation team also included graduate student Susan Curtiss and psychologist James Kent. Upon her initial arrival at UCLA, Genie weighed just 59 pounds and moved with a strange "bunny walk." She often spat and was unable to straighten her arms and legs. Silent, incontinent, and unable to chew, she initially seemed only able to recognize her own name and the word "sorry."

After assessing Genie's emotional and cognitive abilities, Kent described her as "the most profoundly damaged child I've ever seen … Genie's life is a wasteland." Her silence and inability to use language made it difficult to assess her mental abilities, but on tests, she scored at about the level of a 1-year-old.

Genie Wiley's Rehabilitation and the Forbidden Experiment

She soon began to rapidly progress in specific areas, quickly learning how to use the toilet and dress herself. Over the next few months, she began to experience more developmental progress but remained poor in areas such as language. She enjoyed going out on day trips outside of the hospital and explored her new environment with an intensity that amazed her caregivers and strangers alike.

Curtiss suggested that Genie had a strong ability to communicate nonverbally , often receiving gifts from total strangers who seemed to understand the young girl's powerful need to explore the world around her.

Psychiatrist Jay Shurley, MD, helped assess Genie after she was first discovered, and he noted that since situations like hers were so rare, she quickly became the center of a battle between the researchers involved in her case. Arguments over the research and the course of her treatment soon erupted. Genie occasionally spent the night at the home of Jean Butler, one of her teachers.

After an outbreak of measles, Genie was quarantined at her teacher's home. Butler soon became protective and began restricting access to Genie. Other members of the team felt that Butler's goal was to become famous from the case, at one point claiming that Butler had called herself the next Anne Sullivan, the teacher famous for helping Helen Keller learn to communicate.  

Genie was partially treated like an asset and an opportunity for recognition, significantly interfering with their roles, and the researchers fought with each other for access to their perceived power source.

Eventually, Genie was removed from Butler's care and went to live in the home of psychologist David Rigler, where she remained for the next four years. Despite some difficulties, she appeared to do well in the Rigler household. She enjoyed listening to classical music on the piano and loved to draw, often finding it easier to communicate through drawing than through other methods.

After Genie was discovered, a group of researchers began the process of rehabilitation. However, this work also coincided with research to study her ability to acquire and use language. These two interests led to conflicts in her treatment and between the researchers and therapists working on her case.

State Custody (1975-Present)

NIMH withdrew funding in 1974, due to the lack of scientific findings. Linguist Susan Curtiss had found that while Genie could use words, she could not produce grammar. She could not arrange these words in a meaningful way, supporting the idea of a critical period in language development.

Rigler's research was disorganized and largely anecdotal. Without funds to continue the research and care for Genie, she was moved from the Riglers' care.

In 1975, Genie returned to live with her birth mother. When her mother found the task too difficult, Genie was moved through a series of foster homes, where she was often subjected to further abuse and neglect .

Genie’s situation continued to worsen. After spending a significant amount of time in foster homes, she returned to Children’s Hospital. Unfortunately, the progress that had occurred during her first stay had been severely compromised by the subsequent treatment she received in foster care. Genie was afraid to open her mouth and had regressed back into silence.

Genie’s birth mother then sued the Children’s Hospital of Los Angeles and the research team, charging them with excessive testing. While the lawsuit was eventually settled, it raised important questions about the treatment and care of Genie. Did the research interfere with the girl's therapeutic treatment?

Psychiatrist Jay Shurley visited her on her 27th and 29th birthdays and characterized her as largely silent, depressed , and chronically institutionalized. Little is known about Genie's present condition, although an anonymous individual hired a private investigator to track her down in 2000 and described her as happy. But this contrasts with other reports.

Genie Wiley Today

Today, Genie Wiley's whereabouts are unknown; though, if she is still living, she is presumed to be a ward of the state of California, living in an adult care home. As of 2024, Genie would be 66-67 years old.

Part of the reason why Genie's case fascinated psychologists and linguists so deeply was that it presented a unique opportunity to study a hotly contested debate about language development.

Essentially, it boils down to the age-old nature versus nurture debate. Does genetics or environment play a greater role in the development of language?

Nativists believe that the capacity for language is innate, while empiricists suggest that environmental variables play a key role. Nativist Noam Chomsky suggested that acquiring language could not be fully explained by learning alone.

Instead, Chomsky proposed that children are born with a language acquisition device (LAD), an innate ability to understand the principles of language. Once exposed to language, the LAD allows children to learn the language at a remarkable pace.

Critical Periods

Linguist Eric Lenneberg suggests that like many other human behaviors, the ability to acquire language is subject to critical periods. A critical period is a limited span of time during which an organism is sensitive to external stimuli and capable of acquiring certain skills.

According to Lenneberg, the critical period for language acquisition lasts until around age 12. After the onset of puberty, he argued, the organization of the brain becomes set and no longer able to learn and use language in a fully functional manner.

Genie's case presented researchers with a unique opportunity. If given an enriched learning environment, could she overcome her deprived childhood and learn language even though she had missed the critical period?

If Genie could learn language, it would suggest that the critical period hypothesis of language development was wrong. If she could not, it would indicate that Lenneberg's theory was correct.

Despite scoring at the level of a 1-year-old upon her initial assessment, Genie quickly began adding new words to her vocabulary. She started by learning single words and eventually began putting two words together much the way young children do. Curtiss began to feel that Genie would be fully capable of acquiring language.

After a year of treatment, Genie started putting three words together occasionally. In children going through normal language development, this stage is followed by what is known as a language explosion. Children rapidly acquire new words and begin putting them together in novel ways.

Unfortunately, this never happened for Genie. Her language abilities remained stuck at this stage and she appeared unable to apply grammatical rules and use language in a meaningful way. At this point, her progress leveled off and her acquisition of new language halted.

While Genie was able to learn some language after puberty, her inability to use grammar (which Chomsky suggests is what separates human language from animal communication) offers evidence for the critical period hypothesis.

Of course, Genie's case is not so simple. Not only did she miss the critical period for learning language, but she was also horrifically abused. She was malnourished and deprived of cognitive stimulation for most of her childhood.

Researchers were also never able to fully determine if Genie had any pre-existing cognitive deficits. As an infant, a pediatrician had identified her as having some type of mental delay. So researchers were left to wonder whether Genie had experienced cognitive deficits caused by her years of abuse or if she had been born with some degree of intellectual disability.

There are many ethical concerns surrounding Genie's story. Arguments among those in charge of Genie's care and rehabilitation reflect some of these concerns.

"If you want to do rigorous science, then Genie's interests are going to come second some of the time. If you only care about helping Genie, then you wouldn't do a lot of the scientific research," suggested psycholinguist Harlan Lane in the NOVA documentary focused on her life.

In Genie's case, some of the researchers held multiple roles of caretaker-teacher-researcher-housemate. which, by modern standards, we would deem unethical. For example, the Riglers benefitted financially by taking Genie in (David received a large grant and was released from certain duties at the children's hospital without loss of pay). Butler also played a role in removing Genie from the Riglers' home, filing multiple complaints against him.

While Genie's story may be studied for its implications in our understanding of language acquisition and development, it is also a case that will continue to be studied over its serious ethical issues.

"I think future generations are going to study Genie's case not only for what it can teach us about human development but also for what it can teach us about the rewards and the risks of conducting 'the forbidden experiment,'" Lane explained.

Bottom Line

Genie Wiley's story perhaps leaves us with more questions than answers. Though it was difficult for Genie to learn language, she was able to communicate through body language, music, and art once she was in a safe home environment. Unfortunately, we don't know what her progress could have been had adequate care not been taken away from her.

Ultimately, her case is so important for the psychology and research field because we must learn from this experience not to revictimize and exploit the very people we set out to help. This is an important lesson because Genie's original abuse by her parents was perpetuated by the neglect and abandonment she faced later in her life. We must always strive to maintain objectivity and consider the best interest of the subject before our own.

Frequently Asked Questions

Genie, now in her 60s, is believed to be living in an adult care facility in California. Efforts by journalists to learn more about her location and current condition have been rejected by authorities due to confidentiality rules. Curtiss has also reported attempting to contact Genie without success.

Along with her husband, Irene Wiley was charged with abuse, but these charges were eventually dropped. Irene was blind and reportedly mentally ill, so it is believed that Genie's father was the child's primary caretaker. Genie's father, Clark Wiley, also abused his wife and other children. Two of the couple's children died in infancy under suspicious circumstances.

Genie's story suggests that the acquisition of language has a critical period of development. Her case is complex, however, since it is unclear if her language deficits were due to deprivation or if there was an underlying mental disability that played a role. The severe abuse she experienced may have also affected her mental development and language acquisition.

Collection of research materials related to linguistic-psychological studies of Genie (pseudonym) (collection 800) . UCLA Library Special Collections, Charles E. Young Research Library, University of California, Los Angeles.

Schoneberger T. Three myths from the language acquisition literature . Anal Verbal Behav. 2010;26(1):107–131. doi:10.1007/bf03393086

APA Dictionary of Psychology. Language acquisition device . American Psychological Association.

Vanhove J. The critical period hypothesis in second language acquisition: A statistical critique and a reanalysis .  PLoS One . 2013;8(7):e69172. doi:10.1371/journal.pone.0069172

Carroll R. Starved, tortured, forgotten: Genie, the feral child who left a mark on researchers . The Guardian .

James SD. Raised by a tyrant, suffering a sibling's abuse . ABC News .

  NOVA . The secret of the wild child [transcript]. PBS,

Pines M. The civilizing of Genie. In: Kasper LF, ed., Teaching English Through the Disciplines: Psychology . Whittier.

Rolls G.  Classic Case Studies in Psychology (2nd ed.). Hodder Arnold.

Rymer R. Genie: A Scientific Tragedy.  Harper-Collins.

By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

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• Front Cell Neurosci

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Nathalie dehorter.

1 Eccles Institute of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia

Isabel Del Pino

2 Principe Felipe Research Center (Centro de Investigación Principe Felipe, CIPF), Valencia, Spain

Critical periods of brain development are epochs of heightened plasticity driven by environmental influence necessary for normal brain function. Recent studies are beginning to shed light on the possibility that timely interventions during critical periods hold potential to reorient abnormal developmental trajectories in animal models of neurological and neuropsychiatric disorders. In this review, we re-examine the criteria defining critical periods, highlighting the recently discovered mechanisms of developmental plasticity in health and disease. In addition, we touch upon technological improvements for modeling critical periods in human-derived neural networks in vitro . These scientific advances associated with the use of developmental manipulations in the immature brain of animal models are the basic preclinical systems that will allow the future translatability of timely interventions into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD) and schizophrenia.

Introduction

Normal brain function results from a conserved sequence of developmental processes of cell division, migration, network formation and maturation, directed by intrinsic genetic programs as well as by environmental and systemic cues, extrinsic to the nervous system. Within this sequence, appropriate stimuli induce events of heightened plasticity that are required to develop a given function. This capacity of the brain to reorganize during unique developmental time windows in adaptation to the environment has been termed “critical period.”

In the form of electrical activity, experience during development drives the structural and functional organization of neural connectivity (for review Khazipov and Luhmann, 2006 ). The best studied examples have been the critical periods for sensory functions such as ocular dominance (OD) in the visual system. During this period, monocular deprivation induces an OD shift in the visual system (for review Hensch, 2004 ; Levelt and Hübener, 2012 ; Hensch and Quinlan, 2018 ; Hooks and Chen, 2020 ). Electrical activity also controls crucial time windows taking place long before the arrival of sensory-driven stimuli. Since early studies of Galli and Maffei ( 1988 ), it has been shown that patterns of spontaneous activity originating from the developing retina (for review Ford and Feller, 1995 ; Feller, 2012 ) and within local intracortical circuits (for review Siegel et al., 2012 ) participate to the development of visual circuits (for review Arroyo and Feller, 2016 ). Spontaneous patterns of activity intrinsic to the cerebral cortex or arriving from subcortical sources have also been characterized in other sensory systems such as the somatosensory and auditory cortex (Allene et al., 2008 ; Babola et al., 2018 ; Antón-Bolaños et al., 2019 ). These early patterns of activity are thought to operate as checkpoints for the correct implementation of the neuronal circuits and consist of intrinsic voltage-gated calcium currents that are followed by non-synaptic and synapse-driven calcium activities (for review Allene and Cossart, 2010 ). Importantly, they are only observed during specific developmental stages and in a specific sequence (i.e., in the cortex, large plateau assemblies at birth are followed by early network oscillations and giant depolarization potentials) and across regions of the central nervous system such as the spinal cord, the cortex and some subcortical structures (Kirkby et al., 2013 ; for review Ben-Ari, 2008 ; Blankenship and Feller, 2010 ). Previous studies have shown that early spontaneous activity patterns are altered in the neocortex of animal models of neurodevelopmental disorders such as the Fmr1 knock out model of Fragile X syndrome (FXS; Cheyne et al., 2019 ) and the Nr2f1 -deficient model of Bosch-Boonstra-Schaaf optic atrophy syndrome (Del Pino et al., 2020 ) suggesting a link between the early generation of spontaneous activity and abnormal brain development. Although the specific impact of each pattern of early network activity on adult sensory function remains to be thoroughly investigated, this review summarizes recent findings that bring us closer to answer one major question in developmental neurobiology: how does a timely interaction between molecular programs and electrical activity sculpt neural network formation? Acute manipulations in the developing embryo and in in vitro model systems together with transcriptomic data, start to disclose the mechanisms underlying normal and pathological timing of critical periods not only in the sensory and motor systems, but also in associative areas such as the prefrontal cortex (PFC).

Experiences that influence critical periods of plasticity can occur in form of systemic and/or environmental factors of chemical nature such as hormones. Hormones guide behavioral adaptation, adjust the onset of vulnerable time windows and are associated with the transitions in maturational state, including pregnancy, sexual differentiation and puberty (Yamaguchi et al., 2012 ; for review de Kloet et al., 2005 ; Piekarski et al., 2017 ). An important step has been the identification of the tropism of different hormones during developmental transitions. For instance, adequate levels of oxytocin regulate the transient switch of GABA action at birth from excitatory to inhibitory (Tyzio et al., 2006 ), a transient process necessary for correct brain development. Alterations of this critical period of GABA polarity at birth—transiently excitatory GABA instead of inhibitory—have been associated to the pathophysiology of autism spectrum disorders (ASD) such as Fragile X and Rett syndrome (Tyzio et al., 2014 ; Fernandez et al., 2019 ; Lozovaya et al., 2019 ). Thyroid hormones (THs) are also necessary to maintain normal brain maturation and function (for review see Batista and Hensch, 2019 ). However, more studies are needed to thoroughly address the specific influence of hormones on critical periods.

Research on experience-dependent developmental plasticity is leading to a better characterization of “critical periods” and “sensitive periods.” Both terms refer to transient time windows during which specific neural circuits undergo a change in response to environmental factors, affecting brain function. However, a careful consideration for what defines and distinguishes these two types of periods of brain development still requires scientific consensus. Therefore, we would like to briefly elaborate on conceptual frameworks and assumptions underlying the assignment of a transient plasticity event as a “critical” or “sensitive period.” Indeed, it was proposed that “critical periods” differ from “sensitive periods” based on dynamics (Knudsen, 2004 ) i.e., events of gradual plasticity would be classified as “sensitive periods,” while “critical periods” would represent acute shifts during exclusive developmental timepoints in the adaptation of neural systems (White et al., 2013 ). However, a clear explanation of each type of event based on their common and unique features is still lacking. We revised several definitions proposed in the past (for review Rice and Barone, 2000 ; Hensch, 2004 , 2005 ; Knudsen, 2004 ) and reexamined them within the context of the current knowledge.

We propose that a principle that differentiates a “critical” from a “sensitive” period is the ultimate impact on brain structure and function (for review Knudsen, 2004 ). During critical periods, experience instructs neural networks to develop into a configuration that cannot be replaced by alternative connectivity patterns ( Figure 1 , upper panel on the right), leading to irreversible consequences. In other words, a principal feature of a critical period is that it leads to a permanent change necessary for the presence or absence a specific brain function. An example is the input-dependent period for OD, which is necessary for stereopsis and could result in amblyopia (Daw, 1998 ; for review Hensch and Quinlan, 2018 ). During sensitive periods, experience leads to many possible network configurations or connectivity patterns that can compensate for each other and are subjected to remodeling during a protracted period of brain development and adulthood (for review Knudsen, 2004 ; Figure 1 ). Thus, sensitive periods are characterized by experience-dependent plasticity that is not entirely irreversible and that modulates compensatory connectivity patterns. It tunes the degree of performance of a specific function—within a dynamic and functional range—(e.g., orientation and direction preference (Bachatene et al., 2015 ), reopen and shift network function to another state as long as enviromental cues are present.

Principles of critical periods compared to sensitive periods of plasticity. (A) Critical periods in brain development represent narrow time windows of heightened plasticity driven by environmental input. Closure of critical periods is achieved through molecular brakes that constrain plasticity and allow for permanent structural consolidation of one of a few possible connectivity patterns. (B) Sensitive periods in brain development represent broad time windows of gradual change in plasticity driven by environmental input. Sensitive periods are not closed by molecular constrains and can be further reopen by changing environmental cues. The consolidation of one of a broad range of possible patterns of connectivity is reversible and remains functionally dynamic.

In this review, we focus on distinct types of critical periods of brain development. Critical periods that determine axonal growth and neural circuit organization are named here as “ classical critical periods,” because their mechanisms and implications for brain function have been investigated for many years. We also feature recent evidence supporting the idea that critical periods occur long before connectivity rearrangements, acting during embryogenesis and early postnatal stages in mice through fate plasticity during neurogenesis and programmed cell death in post-mitotic neurons, respectively. Here, we explain why the latter are emerging as critical periods. Since fate plasticity and programmed apoptosis may endow the cerebral cortex with transient epochs of flexibility to adjust the absolute numbers and type of neurons of cortical networks in response to environmental cues, we propose to term as “ critical periods for network composition .”

Critical period research has implications beyond a basic understanding of brain formation. It is relevant to continue shedding light on the etiology of neurodevelopmental disorders (Marín, 2016 ). Here, we brought together recent efforts strengthening the link between transient alterations in brain function and the emergence of symptoms of neurodevelopmental disorders, i.e., intellectual disability, ASD and/or schizophrenia. In addition, we feature preclinical studies that support the notion that critical periods could be successfully employed as windows of opportunity for early therapeutic interventions and shift the pathological time-course of a disease model into a normal or asymptomatic neurodevelopmental trajectory. Finally, we provide with a perspective about recent technological advances that model vulnerable time windows reminiscent of human brain maturation in health and disease, and which represent a promising experimental setting to test most suitable therapeutics in major genetic predispositions to neurodevelopmental disorders.

Classical Critical Periods and Critical Periods for Network Composition

Classical critical periods of plasticity have been thoroughly characterized in the visual, somatosensory and auditory systems (Barkat et al., 2011 ; Yang et al., 2012 ; for review Rice and Barone, 2000 ; Hensch, 2004 , 2005 ). Studies in animal models have been key to advance in the discovery of molecular mechanisms and plasticity rules that influence the development of sensory systems, as well as their cross-modal regulation (i.e., effect of the function of one brain modality on the function of another).

The maturation of the visual system results from a highly-regulated sequence of events that occurs long before eye-opening and continues to be sculpted at the onset of eye-opening, upon the arrival of visual inputs (for review Daw, 1998 ; Hooks and Chen, 2007 ). The shift in OD of binocular neurons induced by monocular deprivation, also known as OD plasticity, has been the classical—probably the most studied—model of critical period plasticity, confined to a vulnerable time window [e.g., from P19 to P32 in mice (Gordon and Stryker, 1996 ) and P20-P35 in the rat (Fagiolini et al., 1994 )]. During this critical time frame, the balance in Excitation/Inhibition (E/I) is adjusted to a final configuration in the adult brain (for review Levelt and Hübener, 2012 ; Hensch and Quinlan, 2018 ; Hooks and Chen, 2020 ). The closure of this period is regulated by molecular brakes halting neural plasticity in the primary visual cortex (Gribizis et al., 2019 ). Many of these molecular factors initiating and closing critical period plasticity—such as neuromodulatory signals (e.g., acetylcholine), synaptic proteins [e.g., immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM1)] and components of the extracellular matrix (e.g., perineuronal nets or PNNs)—are influenced by visual experience and act on main neuronal regulators of critical period in the cerebral cortex i.e., GABAergic interneurons expressing parvalbumin and somatostatin (Fagiolini et al., 2004 ; Lyckman et al., 2008 ; Ribic et al., 2019 ; Yaeger et al., 2019 ; Yang, 2020 ; for review Wen et al., 2018 ).

Some of these molecules are known to play a similar role in critical period plasticity of other sensory areas (McRae et al., 2007 ; Nakamura et al., 2009 ; Nowicka et al., 2009 ). Within the somatosensory system, the whisker system represents a well characterized model of defined sequence of critical periods during postnatal development (Rice and Van der Loos, 1977 ; for review Erzurumlu and Gaspar, 2012 ). Parvalbumin interneurons are contributing to activity-dependent changes in the maturation of the somatosensory cortex, during a period spanning from P0 to P14. During this time window, sensory responsiveness and response selectivity to whisker deflections develop in a layer-specific manner within the barrel cortex (van der Bourg et al., 2017 ). Moreover, sensory deprivation remarkably affects the spatial organization of inhibitory circuits (Lo et al., 2017 ). In addition to somatosensory input-dependent plasticity—involving NMDA and GABA receptor function and being largely altered by whisker deprivation in the barrel cortex and other relay stations during postnatal stages (Pan et al., 2017 )—a recent study reports that spontaneous network activity from thalamic inputs at embryonic stages is also fundamental for somatotopic map development (Antón-Bolaños et al., 2019 ).

In the primary auditory cortex, a vulnerable period for spectral tuning extends from about P11 to P13 in rat (de Villers-Sidani et al., 2007 ), followed by another sensitive window, during which the auditory system remains maximally plastic—e.g., P31-P38 in mice (Bhumika et al., 2020 ), 3.5 years in humans (Sharma et al., 2002 ). These plastic periods are dependent on the stimulus complexity sculpting the tonotopic organization of the auditory cortex. The environmental influence (or lack of it) in the auditory system has a different impact on the acquisition of hearing depending on the developmental stage. Specifically, hearing loss induced at postnatal day 10 in mice, has greater impact than after sexual maturation (Buran et al., 2014 ). In the cortex, tonotopic maps are modelled during early life to adapt to the surrounding environment (de Villers-Sidani et al., 2008 ). The primary auditory cortex is a key hub where neuromodulatory and topographically-organized thalamic inputs meet to tune the cortical layers below. The control of the duration and closure of the vulnerable periods is dependent on the local state of cortical maturation. In particular, inhibitory interneurons in layer 1 (L1) send narrowly descending projections to differentially modulate thalamic drive onto pyramidal and parvalbumin-expressing (PV) cells in L4, creating brief windows of intracolumnar activation. Silencing specific subtypes of L1 interneurons, abolishes map plasticity during the tonotopic critical period (Takesian et al., 2018 ).

The role of non-neuronal brain cells in critical period plasticity has been less addressed. Oligodendrocyte-neurons interaction through Nogo-66 receptor drive the maturation of intracortical myelination necessary for the closure of OD and auditory plasticity (McGee et al., 2005 ; Kalish et al., 2020 ) and might be also a hallmark of critical period conclusion outside sensory modalities. Regions such as the PFC undergo a change in oligodendrocyte maturation and myelination following deprivation of social behavior in mice after weaning (Makinodan et al., 2012 , 2016 ). Of special relevance are single cell RNA sequencing approaches that are accelerating our understanding of the molecular programs implemented by all brain cell types during critical periods. A pioneer effort employed single-cell RNAseq analysis during critical period for tonotopic topography in the primary auditory cortex and provides with a detailed transcriptomic profile of each neuronal and non-neuronal cell type during this critical period for auditory plasticity (Kalish et al., 2020 ). Following on previous studies describing the role of astrocyte maturation and microglia function in OD plasticity (Müller, 1990 ; Singh et al., 2016 ; Sipe et al., 2016 ), the study of Kalish et al. ( 2020 ) substantiates evidences that activation of astrocytes and microglia contribute to critical period plasticity in the neocortex.

The sequence of critical periods of a specific sensory function unfold in coordination with other sensory modalities. The influence of the maturation of one sensory system on another is known as cross-modal or cross-sensory plasticity (for review Morrone, 2010 ). Initial studies showed that the homeostatic scaling of synaptic plasticity underlies this form of plasticity in sensory areas such as the auditory cortex as well as somatosensory cortices following visual deprivation (Goel et al., 2006 ; He et al., 2012 ). Importantly, cross-modal plasticity may also arise outside of the early developmental phase. Plasticity induced by visual deprivation in adult mice results in a potentiation of thalamo-cortical synapses reaching the auditory cortex and leads to an improved processing of the auditory information (Petrus et al., 2014 ). This indicates that cross-modal plasticity drives the onset of a critical period of synaptic scaling in a brain-region specific manner (i.e., in thalamocortical axons of the auditory cortex, but not of the visual cortex). Further efforts in the study of cross-modal plasticity are fundamental to better understand how critical periods of different brain regions sculpt sensory and high-order brain functions, early in the immature brain (Nardou et al., 2019 ).

Before experience-driven critical periods sculpt neural wiring in the postnatal brain, exposure to cytotoxic agents has been used to identify timepoints during which cell proliferation, migration, differentiation and apoptosis are susceptible to change (for review Rice and Barone, 2000 ; Figure 2 ). Recent studies have unveiled new molecular mechanisms acting in immature cell types during neurogenesis and programmed cell death. New evidences suggest that neurogenic fate and programmed cell death might be influenced by their surrounding milieu as well as by electrical activity (Blanquie et al., 2017 ; Vitali et al., 2018 ; Wong et al., 2018 ; Oberst et al., 2019 ). In the following section, we highlight recently discovered features that characterize developmental plasticity events in neurogenesis and apoptosis and that extend beyond previous criteria that define a classical critical period (for review Hensch, 2004 ).

Critical events during embryonic and postnatal periods of brain development that impact adult brain function. Scheme shows a timeline of the key stages in the development of neuronal networks in the mouse brain (embryonic critical period: E12 to E18; Perinatal critical period: P0-P10; late postnatal critical period: P10-P40). It summarizes the events that occur during brain maturation and leads to long-term alterations. OD, ocular dominance; ENOs, early network oscillations; GDP, giant depolarizing potentials; GABA, switch from excitatory to inhibitory.

During corticogenesis in the embryonic brain, apical progenitors give rise to pyramidal neurons in an “inside-out” fashion—first deep, later superficial (Cadwell et al., 2019 ). Intrinsically-regulated genetic programs in apical progenitors guide their temporal progression in neurogenic fate from early states—in which they generate early-born deep layer pyramidal neurons—to a late state—in which they give rise to late-born upper layer pyramidal cells ( Figure 3 ; Telley et al., 2016 ). Multiple findings from loss-of-function approaches of specific transcription factors suggest that apical progenitors are competent to re-enter a previous neurogenic state, in other words, to rewind their temporal neurogenic state, i.e., to convert into a different progenitor type, a process known as “ fate plasticity ” ( Figure 3 ). For example, the transcription factor Foxg1 has been shown to regulate at the embryonic stage (E)13.5, the ability of apical progenitors to revert to an earlier neurogenic competence and to generate early-born Cajal-Retzius cells, instead of deep-layer pyramidal neurons (Hanashima et al., 2004 ; Shen et al., 2006 ). Interestingly, recent studies support the idea that fate plasticity might be regulated not only by intrinsic genetic programs (for review Greig et al., 2013 ), but by the bioelectric membrane properties as well as in response to cell-extrinsic factors, in a non-cell autonomous manner (Vitali et al., 2018 ; Figure 3 ). Fate plasticity is also specific for different progenitor types and specific of a time point in corticogenesis. In contrast to intermediate progenitors—displaying an immutable temporal progression of neurogenic fate—apical progenitors at embryonic stage (E)15.5 can re-enter a past molecular state—from E15.5 neurogenic state to E12.5—giving rise to additional deep-layer neurons within their progeny (Oberst et al., 2019 ). Thus, fate plasticity of apical progenitors could meet several principles that define a critical period (for review Hensch, 2004 ). The first principle is the influence by the environment. It has been shown that fate plasticity is dependent on the resting membrane potential of radial glia (Vitali et al., 2018 ), their metabolic states (Khacho et al., 2016 ; Knobloch et al., 2017 ; for review Knobloch and Jessberger, 2017 ) and the feedback signaling from neighboring postmitotic neurons (Seuntjens et al., 2009 ; Toma et al., 2014 ). This suggests that fate plasticity could be influenced by surrounding factors regulating apical progenitor’s microenvironment, such as the availability and distribution of ions and metabolites that constitute the electrochemical gradient and determine the energetic states of these cells. A second principle met by fate plasticity of apical progenitors is its occurrence during a unique time window in embryonic development: apical progenitors are a transient cell type that displays fate plasticity at embryonic stage (E) 15.5. A third principle of a critical period is the irreversible effects on brain function. Although fate plasticity is a process that will generate higher numbers of deep-layer cortical neurons (i.e layers 5–6), instead of upper-layer ones (i.e., layers 1–4) irreversibly, the precise consequences of fate plasticity for adult brain function remain to be elucidated. In addition, since the generation of astrocytes and oligodendrocytes follows neurogenesis and continues during the first postnatal month in the mouse brain (Bayraktar et al., 2014 ; for review Bergles and Richardson, 2015 ), an unanswered question is whether fate plasticity of radial progenitors could also impact the production of non-neuronal cells in the cerebral cortex. It is easy to speculate that if the generation of high numbers of deep-layer pyramidal neurons occurs at the expense of upper-layers neurons and glia, fate plasticity could have a significant impact on cortical computation and on the regulation of subsequent critical periods.

Fate plasticity during corticogenesis. (A) Schematic of corticogenesis (left panel) showing three populations of progenitor cells: neuroepithelial cells (in black), apical progenitors (light blue) and intermediate progenitors (dark blue). Apical progenitors (radial glia) within the ventricular zone (VZ) initially expand their population and generate neurons and intermediate progenitors. As corticogenesis proceeds, intermediate progenitors (within the SVZ) as well as apical progenitors generate neurons. (B) Temporal progression of neurogenic stage (right panel) shows apical progenitors around embryonic stage (E) 12.5 that give rise to early born deep-layer pyramidal neurons. In the standard temporal progression of corticogenesis apical progenitors at E15.5 give rise to late-born upper-layer pyramidal neurons. Apical progenitors at E15.5 can change their neurogenic state, a process named “fate plasticity” and give rise to late-born deep-layer pyramidal neurons under specific conditions such as cell hyperpolarization or reactivation of Wnt-signaling. VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate; MZ, marginal zone; V rest , resting membrane potential.

Programmed cell death in the postnatal brain is also a critical period for network composition. The immature brain generates a surplus of cells necessary to guide specific processes during development. Intrinsic molecular programs initiated by the pro-apoptotic factors of Bcl2-associated X protein (Bax) and Bcl2 antagonist/killer (Bak) render specific cell populations susceptible to undergo cell death during brain development (Southwell et al., 2012 ). Brain cells undergo massive elimination during two waves of apoptosis that take place from the embryonic stage E14 and between P6 and P10 in mice ( Figure 2 ; for review Wong and Marin, 2019 ). In contrast to previously reported cell-autonomous regulation of cell death (Southwell et al., 2012 ), new evidence suggests that specific patterns of postnatal network activity establish the onset, duration and extent of neuronal apoptosis (Blanquie et al., 2017 ; Denaxa et al., 2018 ; Priya et al., 2018 ; Wong et al., 2018 ; Duan et al., 2020 ). Recent work identified two molecular pathways guiding the selection process that determines neuron survival and sets the final composition of a neural network in the cerebral cortex: the calcium-dependent phosphatase Calcineurin, that translates the arrival of electrical activity into molecular cascades of cell survival (Priya et al., 2018 ), and the phosphatase tensin homolog protein (PTEN), that sets the clock for the death of the GABAergic interneurons in the absence of incoming activity from pyramidal neurons (Wong et al., 2018 ). Neuronal numbers significantly decrease during the first two postnatal weeks, reaching a plateau in adulthood in the neocortex (Blanquie et al., 2017 ; Denaxa et al., 2018 ; Priya et al., 2018 ; Wong et al., 2018 ). As apoptotic neurons cannot be replaced, programmed cell death in the postnatal brain is an irreversible process. The main feature that differentiates programmed cell death from classical critical periods is the functional consequence of postnatal apoptosis for cortical network response. In classical critical periods, the functional competence of inputs determines the selection of a specific pattern of connectivity. Yet, during programmed cell death, the functional competence of inputs determines the final number of neurons and the relative contribution of GABAergic and glutamatergic neuronal types to the neural network. Therefore, it is conceivable to believe that changes in neuronal number (through “ critical periods for network composition ”) could have a different impact on the dimensionality of neural responses than changes in connectivity patterns (through “ classical critical periods ”). Currently, it is unclear how programmed cell death of postnatal neurons precisely influences information processing in the cerebral cortex. However, initial studies performed in mice demonstrate that manipulating the number of excitatory pyramidal neurons in the cerebral cortex results in permanent consequences for brain function and behavior. Glutamatergic neuron overproduction as well as increased glutamatergic neuron apoptosis result in altered motor learning, hyperactivity or phenotypes reminiscent of autism-like traits (e.g., altered social behavior and repetitive behavior; (Fang et al., 2014 ; Nakamura et al., 2016 ). Moreover, programmed cell death significantly changes the size of the visual cortex leading to smaller, but functional, retinotopic map (Nakamura et al., 2016 ). These findings suggest that programmed cell death during postnatal stages is a critical period for high-order complex behavior such as social behavior, and motor learning. Further studies should unveil whether programmed cell death in postmitotic glutamatergic neurons is a critical period for sensory (e.g., visual) function.

Manipulating Critical Periods to Shift Developmental Trajectories

In the context of disease, knowledge of critical period plasticity shows promise to restore specific aspects of brain function in animal models of neurological disorders. Control of critical period plasticity can be implemented in two different ways: by reopening critical periods in the adult brain—which is the most common strategy—and by prematurely closing the periods of abnormal plasticity through timely intervention in the early developing brain, requiring more sophisticated experimental designs. In the following section, we highlight recent pre-clinical studies that illustrate the therapeutic potential of these two timely strategies targeting developmental plasticity specific to critical periods.

The reactivation of restricted periods of plasticity in adulthood represents both an episode of vulnerability and opportunity for therapeutic intervention (for review Hensch and Bilimoria, 2012 ; Marín, 2016 ). The main advantage of thoroughly understanding critical periods is to be able to manipulate their onset, duration, and closure to ultimately control heightened levels of brain plasticity. The identification of molecular mechanisms regulating critical periods in the developing brain has been a key stepping-stone towards unveiling approaches that control the reopening of heightened plasticity after closure of the developmental plasticity period. Numerous approaches through which critical windows—and thus brain malleability—might be re-opened in adults have been attempted in animal models. Molecular factors, such as the endogenous inhibitor for nicotinic acetylcholine receptor—Lynx1—and other components of the extracellular matrix, i.e., perineuronal nets (PNNs), set the closure of OD plasticity and limit plasticity in the adult visual cortex (Pizzorusso et al., 2002 ; Morishita et al., 2010 ; for review Hensch, 2005 ; Fawcett et al., 2019 ; Yang, 2020 ). These factors are key for the maintenance of network activity (Favuzzi et al., 2017 ; Faini et al., 2018 ) and brain plasticity (Bradshaw et al., 2018 ). Moreover, these molecules not only regulate critical periods in sensory function, they also participate in the regulation of critical periods related to complex cognitive demands such as the storage of emotional memories (for review Nabel and Morishita, 2013 ). In particular, PNNs mediate the closure of critical period of permanent fear memory extinction (Xue et al., 2014 ; Slaker et al., 2015 ). Removal of PNNs resets the mature neural network to an immature, juvenile state, by decreasing network inhibition and increased gamma activity (Lensjø et al., 2017 ). Control of critical period plasticity through PNN regulation in other brain regions influences brain function beyond sensory-motor and complex behaviors. In animal models of obesity and diabetes, critical period for leptin-dependent development of the hypothalamic acuate nucleus—involved in metabolic homeostasis—is accompanied by a reorganization of PNNs around leptin-receptor positive GABAergic neurons (Mirzadeh et al., 2019 ). Thus, PNNs remain central molecular hallmarks in the study of critical periods associated to the pathophysiology and the treatment of a range of neuropsychiatric disorders and related metabolic comorbidities (Bradshaw et al., 2018 ; for review Wen et al., 2018 ).

Other approaches took advantage of molecules with a synaptic function that participate to critical periods of synaptic plasticity during a specific time window for social reward learning. In particular, oxytocin-mediated long-term depression in the nucleus accumbens is reopened by a single dose of 3,4-Methyl enedioxy methamphetamine in young adult mice (MDMA, commonly known as ecstasy; (Nardou et al., 2019 ). Consequently, activation of the oxytocin receptors by MDMA showed potential to restore impaired social behavior and social-related disorders in animal models of neurodevelopmental disease. Other studies reported that drug-induced reopening of critical period plasticity specifically improves the function of sensory systems. For example, valproic acid—an histone deacetylase inhibitor affecting synaptic neurotransmission and primarily used to treat epilepsy—has been shown to restore visual acuity in animals that underwent monocular deprivation (Silingardi et al., 2010 ). Valproic acid has also been shown to participate to the reopening of the critical-period learning of absolute pitch in humans (Gervain et al., 2013 ).

Additional experimental strategies involve the direct manipulation of inhibitory GABAergic circuits. Inhibitory interneurons are central arbiters of critical period plasticity and direct the competition between electrical activity and patterns of connectivity setting plasticity onset and duration (Toyoizumi et al., 2013 ; Tang et al., 2014 ; Isstas et al., 2017 ). Specific subpopulations of inhibitory interneurons define the tempo of experience-dependent critical period in the cerebral cortex (for review Hensch, 2005 ). Fast-spiking PV-cells have the potential to remain plastic even beyond the peak of natural critical periods (Morishita et al., 2015 ). The transient increase of parvalbumin interneuron activity with pharmacological approaches (diazepam) or with approaches that employ synaptogenic molecules to increase synaptic excitatory input onto PV cells—through exogenous application of Neuregulin1, a ligand of the interneuron-specific transmembrane receptor ErbB4—prevent OD plasticity after visual monocular deprivation (Kuhlman et al., 2013 ; Sun et al., 2016 ). Pharmacological or chemogenetic approaches that increase PV interneuron activity have also been shown to restore control-like neural activity (CA1 network dynamics) and behavior (cognitive function) in different mouse lines modeling mutations associated to schizophrenia (Marissal et al., 2018 ; Mukherjee et al., 2019 ).

Failure to stabilize neural circuits and reducing plasticity as the brain develops underlies the physiopathology of a range of neurodevelopmental disorders. One example is delayed critical period for GABA polarity in the FXS mouse model (also known as Fmr1 deficient mice; He et al., 2014 ) and in mouse models of Rett syndrome ( Mecp2 deficient mice) displaying abnormal GABA polarity in the hippocampus (excitatory GABA instead of inhibitory), until very late in brain development (i.e., P15 in mice (Lozovaya et al., 2019 ). In addition, Fmr1 deficient mouse models of FXS are also characterized by a delayed progression of critical periods in the somatosensory system (Bureau et al., 2008 ; Harlow et al., 2010 ; Till et al., 2012 ). Interestingly, precocious onset and closure of critical period in the visual cortex has been reported in Mecp2 deficient mice (Durand et al., 2012 ; Krishnan et al., 2015 ). In order to prematurely advance, constrain or delay critical periods of plasticity, acute experimental strategies have been employed to reorient abnormal immature brain states towards a normal developmental trajectory. One of these strategies took advantage of timely manipulations of GABA action during early postnatal development or around birth, through the inhibition of the Na + /K + Cl − cotransporter 1 (with NKCC1 inhibitors, i.e., bumetanide). These efforts normalized somatosensory whisker-evoked responses and GABA polarity in the mouse hippocampus of the FXS mouse model (He et al., 2019 ). Altogether these recent findings illustrate how a better knowledge on critical period regulation could be employed (e.g., by re-opening or tuning the degree of plasticity) to develop timely applied strategies that lessen disease-relevant symptoms.

Modeling Critical Periods of Plasticity with New Technologies

Mouse genetics are a fundamental asset to study the influence of gene-environment relationship on critical periods (Xu et al., 2019 ). They still remain a key tool to probe the genetic, cellular and neural circuits basis of pathophysiological states of human neurodevelopmental disorders (for review Marín, 2016 ; Del Pino et al., 2018 ). The advent of CRISPR-Cas9 mediated gene editing technology has significantly increased the spectrum of animal models available for the study of neurodevelopmental disease, using either rodents but, also recently, non-human primates. A recent study revealed that CRISPR-designed macaque monkeys, mutant for the Shank3 gene, exhibited sleep disturbances, motor deficits and increased repetitive behavior, as well as social and learning impairments (Zhou et al., 2019 ). Similarly, lentivirus-mediated transgenic monkeys expressing human MeCP2 in the brain exhibit autistic-like behavior and show germline transmission of the transgene (Liu et al., 2016 ). Whilst the use of non-human primates as animal models provides some scientific benefits to further unveil critical period plasticity mechanisms underpinning human disorder-like pathophysiology, we focus here on cutting-edge technological advances that will importantly contribute to model critical periods of the human brain.

Reconstructing the developmental trajectories of human cortical circuits in vitro has the potential to revolutionize our understanding of vulnerable periods in human brain development (Chukwurah et al., 2019 ; Marshall and Mason, 2019 ; for review Quadrato et al., 2016 ). In order to fill the gap between human disease and model organisms, the development of stem cell technologies—both embryonic and induced pluripotent stem cells (iPSCs)—have given access to functional readouts typical of early stages of human brain development (Dolmetsch and Geschwind, 2011 ). iPSCs have provided insights into the cellular alterations underlying neuropsychiatric disorders such as autism and schizophrenia (Marchetto et al., 2017 ; Adhya et al., 2020 ; reviewed in Ben-Reuven and Reiner, 2016 ; Vitrac and Cloëz-Tayarani, 2018 ). Although concerns have been raised regarding the clinical applications of iPSCs as a valuable source for cell transplantation therapy and the significant reprogramming variability of human-derived iPSCs, the simplicity of two-dimensional cultures is suitable for mechanistic studies, large-scale screening, or high-throughput drug testing. However, modeling critical period in vitro requires a better system that recapitulates the processes of proliferation, patterning, cell fate progression, migration and connectivity rearrangement of neural networks composed of distinct cell types and organized into different layers and different systems. It also demands an approach that will ultimately include environmental cues influencing different levels of plasticity during protracted periods of time.

The generation of three-dimensional (3-D) brain organoids, derived from human induced pluripotent stem cells (iPSCs), resolved the long-standing limitations of a 2D approach and provide unprecedented opportunity to understand neurobiological mechanisms of human brain development in health and disease. Currently, 3D brain organoids have a demonstrated validity to model basic features of the human embryonic neural tissue and critical steps of early brain development such as neurogenesis, neuronal migration and neuroanatomical features—upper and deep layer neurons—specific of brain tissue (reviewed in Paşca, 2018 ; Seto and Eiraku, 2019 ; Benito-Kwiecinski and Lancaster, 2020 ; Tambalo and Lodato, 2020 ; Velasco et al., 2020 ). Important advances in the engineering of brain organoids have also resolved long-standing limitations in size reproducibility and in the production of neuronal diversity which closely resembles the one found in in vivo embryogenesis (Velasco et al., 2019 ). Nevertheless, 3D brain organoids present some limitations, namely the inability to reproduce the exact cell type diversity and radial glia maturation (Bhaduri et al., 2020 ). It also remains unclear whether fate plasticity in cortical radial glia can be probed in brain organoids. Despite these constraints, brain organoids are suitable to replicate some developmental processes of the human brain such as the transcriptional regulation of neural progenitor cell fate, altered in pathology such as ASD (Mariani et al., 2015 ). Moreover, brain organoids composed of iPSC derived from pallial (cortical) and sub-pallial (subcortical) domains, also named 3-D cerebral assembloids, have been utilized to model tangential migration of interneurons (Bagley et al., 2017 ; Birey et al., 2017 ; Xiang et al., 2017 ) and reciprocal cortico-thalamic connectivity (Xiang et al., 2019 ; Figure 4 ). Interestingly, cerebral assembloids derived from cells of patients with Timothy syndrome—a severe neurodevelopmental disease characterized by ASD and epilepsy—were used to demonstrate that GABAergic interneurons exhibit prominent migratory defects (Birey et al., 2017 ).

3D brain organoids for modeling human brain development and neurodevelopmental disorders in vitro . Cerebral organoids are 3D brain models derived from human induced-pluripotent stem cells (iPSCs). 3-D brain organoids generated by Velasco et al. ( 2019 ; top panel) are consistent in size and reproducibly present a spectrum of cell types. 3-D cerebral assembloids (middle panel) are formed of a pallium-like organoid (dorsal) and a subpallium-like organoid (ventral) and can recapitulate GABAergic interneuron migration. Air-liquid interface cerebral organoids (ALI-Cos; bottom panel) show an improved neural survival and can therefore be suitable to assay critical periods of programmed cell death. Neurons within ALI-COs form axon bundles over long-distances mimicking long-range projections.

In order to bypass limitations of brain organoids in neuronal survival and axonal growth, further efforts implemented new culturing methods, such as the air-liquid interface cerebral organoids (ALI-COs). ALI-COs have been useful in the generation of brain organoids with specific features more reminiscent of in vivo neural networks, such as the formation of functional axonal bundles spanning long-range—longer than in other brain organoids—projections (Giandomenico et al., 2019 ). It remains to be determined to which extent 3D brain organoids, ALI-Cos or 3-D cerebral assembloids can recapitulate the key periods of fate plasticity, embryonic and postnatal programmed cell death, intrinsic network activity, as well as input-dependent network plasticity. Neuron-glia interactions and presence or absence of mesoderm-derived progenitors giving rise to microglia represent sources of variability in these preparations (Ormel et al., 2018 ). Therefore, touching upon the role of glia when modeling vulnerable windows of plasticity in brain organoids is very complex and should be the subject of discussion of experts in the field.

Current challenges of the in vitro brain organoid systems to model critical periods require further systematic efforts to reliable model the emergence of network activity patterns and new approaches that mimic environmental influences together with techniques tailored to measure their long-term consequences in organoid culture conditions. So far, brain organoid preparations display spontaneous neural activity (Eiraku et al., 2008 ; Quadrato et al., 2017 ; Giandomenico et al., 2019 ). Mouse-derived brain organoids display robust network activity synchronization resembling an immature form of functional organization (Eiraku et al., 2008 ), but neither it has been shown whether human-derived brain organoids consistently display synchronized network activity within the same type of preparations (Quadrato et al., 2017 ) nor it is known whether they recapitulate the sequence of coordinate network activity observed in vivo (Giandomenico et al., 2019 ). It was suggested that brain organoid activity could be tailored to a specific activity pattern using optogenetics (Velasco et al., 2020 ). Imposing a specific activity pattern to brain organoids could be indeed useful to better understand the logic behind the interplay between electrical activity and molecular programs specific to human brain development. Nevertheless, an in-depth characterization of network activity patterns intrinsically displayed by brain organoids across time needs to be performed. For example, recent studies showed robust synchronized network activity in human-derived brain organoid cells, when cells were dissociated and plated anew (Sakaguchi et al., 2019 ) and giant-depolarization potential-like events are displayed by a newly developed type of neuronal organoid preparation known as Bioengineered Neuronal Organoid (BENO; Zafeiriou et al., 2020 ). Yet, comparative molecular profiling and connectivity rules of highly synchronized brain organoids vs. non-synchronized ones will further elucidate neurobiological aspects supporting early patterns of intrinsic network activity in the human brain. The field will profit from a standardization of the cellular components and environmental cues (culturing conditions) necessary for brain organoids to display the synchronized network activity patterns found in vivo .

In addition, some aspects of the environmental cues influencing early critical periods could be easily probed in human embryonic stem cell-derived brain organoids. Human-derived neurons within BENOs display the developmental switch in GABA polarity found in the developing mouse brain (Zafeiriou et al., 2020 ). Regulation of critical period for GABA polarity by experience in form of hormonal stimuli could be easily modeled and should be tested through the addition of different concentrations of oxytocin to BENOs during the time period in which GABA is excitatory.

Modeling critical periods of sensory systems typically occurring during early childhood (or early adult mice) in a dish faces many technical challenges and will probably require of brain assembloid technology. Brain organoid preparations containing photoreceptor-like cells and forebrain-like structures, display neural activity in response to light stimuli (Quadrato et al., 2017 ). The advent of sophisticated experimental designs that combine multiple region-specific organoids together with optogenetic stimulation is necessary to make progress on this front. Exciting times in which basic aspects of cortico-thalamic plasticity can be deconstructed into assembloids containing multiples organoids—e.g., future retina-thalamic-cortical assembloids or bi-thalamic-cortical assembloids—aided by a focal optogenetic stimulation (or controlled environmental conditions) is one of many speculative examples that could help to better assess gene/environment interactions during precise developmental periods. This will unveil if 3D brain organoid/assembloids can recapitulate cellular and molecular hallmarks of classical critical periods, which will ultimately determine the degree of validity of this in vitro system as model of human brain development.

Critical periods hold potential to reinstate brain function. We provide a perspective on how the different aspects of critical period research paves the way for potential disease-modifying therapeutic strategies in neurodevelopmental disorders. Timely interventions during specific developmental windows restore network activity or behavior in animal models, thus reinforcing the notion that critical episodes of developmental plasticity can be used as unique windows of therapeutic opportunity to reorient pathophysiological states towards a “normal” developmental path (Marín, 2016 ). Critical period research raises important considerations for the well-timed administration of therapeutic strategies during precise developmental windows. The goal of timely applied interventions is to reduce undesired trade-off effects of therapeutic strategies utilized during a protracted period within brain development or after brain maturation. Only a sound understanding of the order, time-line and cross-regulations of critical periods in normal and pathological trajectories will help us find the most precise, effective and age-specific therapeutic intervention to follow. With the hope that interventions during specific time windows could significantly help to reduce symptoms in adulthood, further efforts to unveil molecules that reopen or close critical period plasticity will definitely expand the potential clinical relevance of timely interventions during development.

A key challenge to further understand the time-course of vulnerable periods during brain formation is the study of sex-specific differences. A wealth of data demonstrates that the critical period of sexual differentiation in the brain starts in the embryonic brain (from E16 to P4 in mice and second trimester in human; McCarthy et al., 2018 ). However, there is still very limited information regarding how it influences the time course of subsequent critical periods in males compared to females. Therefore, differentiating sex-specific developmental trajectories represents a major milestone that must be addressed. It is not expected that the timeline of critical periods would be shifted in very basic sensory modalities. However, one could expect that the temporal unfolding of vulnerable periods that determine a different degree of performance of high-order functions to be singular for each sex. Descriptions of sexual differences in brain function show that the temporal extent of sensitive periods for social learning is delayed in males, compared to females (Nardou et al., 2019 ). The underlying neurobiological basis remains largely underexplored, e.g., the influence of the thyroid gland, expressing both estrogen and androgen receptors on vulnerable periods (Batista and Hensch, 2019 ). Understanding how hormones impact vulnerable periods in a sex-specific manner is the first step towards the development of personalized medicine. More basic research on gender-specific neurodevelopment is also expected to precisely unveil predisposition and susceptibility of each sex to brain disease, within a framework that encompasses the life-experience of the individual.

Finally, careful classification of vulnerable periods as “critical” or “sensitive” has implications beyond basic research. Policymakers, psychosocial therapies and educational aid programs for early childhood adversity should be guided by the scientific advances in critical period research (see recent review Nelson and Gabard-Durnam, 2020 ). Specially now, in light of the current challenges posed by the COVID19 pandemic, measures of confinement and social distancing on millions of healthy children and children with neurodevelopmental disorders are lacking a consensus feedback from the scientific community (Arango, 2020 ). This is mirrored by a worrisome scenario in which governments apply very different measures that raised skepticism and questions such as: How long could we implement confinement measures while maintaining neuropsychiatric well-being in each age-group of children? Are the potential long-term consequences of confinement in children with neurodevelopmental disorders—such as ASD—exceeding the risk of COVID19 infection? (Aledo-Serrano et al., 2020 ). A better understanding of critical periods as opposed to sensitive periods is fundamental to instruct these policies, considering the implications for mental health of the next generations.

Author Contributions

ND and ID contributed equally.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We would like to thank Rhys Knowles, Dr. Luke Noon, Dr. Ángel Aledo-Serrano and Dr. Khalil Kass-Youssef for their comments.

Funding. The work was supported by the Australian National University to ND and by the Spanish Ministry of Science, Innovation and Universities (Ministerio de Ciencia, Innovación y Universidades, RTI2018-100872-J-I00) as well as the CIDEGENT excellence research program of the Valencian regional government (CIDENGENT/2019/044) to ID.

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