COGS 200 Group 16

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Look Who's Talking: The effects of GABAergic deficits on children's overall language development


INTRODUCTION
We postulate that as depression is associated with reduced GABA levels in the patient, there will therefore be a decreased placental expression of GABA. We claim this decline in placental GABA expression will lead to insufficient excitatory signaling during prenatal development, and decreased inhibitory signalling during the postnatal development in the infant, which will further result in a delayed onset and offset of critical periods (CPs). We will measure placental GABA levels and test its effects on CP timing in infants. Dependant on our results, inspecting any further developmental abnormalities related to language acquisition and depression can be done as further analysis.

We believe that this study will fill an important gap in the psycholinguistic field. Multiple aspects of depression and its effect on language development have been studied, however, these aspects have primarily been examined in isolation, rather than looking at their collective impacts on infant language development. As a result, our study aims to investigate ‘the bigger picture’.

There are a multitude of reasons why it is crucial to conduct the study in the way we propose, and why it is important in and of itself. Essentially, since perceptual development in a native language is sequential (Werker & Hensch, 2015), it has been proposed that each stage in this development builds off of the previous stages. Thus, if there are any complications in any of the stages, the subsequent stage(s) may be affected, which ultimately will affect the child’s overall language development (this will be discussed later on in the body of this proposal). The shifting of critical periods - essential points in language development, especially that of speech perception (Johnson & Newport, 1989; Lenneberg, 1967) - due to a decrease in GABA levels suggests how one stage may be affected. Furthermore, while there is numerous existing literature on language development and mothers with postpartum depression (Bernard-Bonnin, 2004; Mombereau et al., 2005), there is a limited amount of literature that examines the effects of maternal depression (before and during childbirth) on the child after birth. What remains to be seen, and therefore what we aim to investigate, are the long-term effects this may have on a child’s overall development from infancy to pre-kindergarten, if any. In addition to this, there is not a considerable amount of literature tracking the long-term language development of children, particularly in relation to the coupling of maternal depression and the decrease in GABA levels, and the resulting shift in CPs.

As well, if our hypothesis is correct in that GABA levels can impede language development, our longitudinal research can shed some light on the early stages and or symptoms of speech disorders. One of the main aspects of our proposed research is phonological awareness, which is the keystone of literacy, as it is greatly predicative of a child’s ability to read and spell (Nation & Hulme, 1997). In fact, deficits in phonological awareness is a characteristic of disorders such as dyslexia (Swan, 1997; Lyon, 2003). Some abnormalities that may be identified in children within our research, such as regularly omitting, substituting, and distorting phonemes, despite the fact that they may be able to say these phonemes in isolation, are typical of speech sound disorder (Haiyou-Thomas et al., 2016). In identifying atypical language errors, we hope that our research will be able to preempt further development of such disorder and or other disorders of the like, and lead to further investigation of the relation between maternal depression and specific speech disorders.

In short, our proposed study is valuable to the scientific community as it combines the features of multiple past studies to form a more comprehensive overview of the effect of GABA levels on CPs of language development.

GABA and Depression
1.1 Background
Depression is a prevalent disorder in today's society and it exhibits a high comorbidity rate with stress and anxiety disorders. Despite the fact that its causes and its exact mechanism remains unclear in the scientific literature, there have been different theories to explain the effects and causes of the depression in the human brain. For example, the cause of depression is widely attributed and correlated with the deficit in monoaminergic systems: networks of neurons that use monoamine neurotransmitters such as serotonin or norepinephrine. In particular, decrease in serotonin levels has been shown to have a prominent role in the depression and many commonly known antidepressants (ADs) function to compensate for this serotonergic deficit by increasing the extracellular concentration and function of monoamine neurotransmitters (Albert & Benkelfat, 2012; Albert & Benkelfat, 2013).

1.2 Biology
Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the mammalian central nervous system. The GABAergic deficit hypothesis of major depressive disorders (MDD), is a recent theory which treats MDD as a stress disorder. Its claim is based on the evidence that stress is shown to be a vulnerability factor in mood disorders such as MDD. Patients diagnosed with MDD often have an altered hypothalamic–pituitary–adrenal axis (commonly referred to as the HPA-axis, which is usually associated with stress response) function (Holsboer, 2001) and polymorphisms in CRH1 (corticotropin releasing hormone) receptor gene. Additionally, these are associated with increased cortisol, a stress hormone, levels (Binder & Nemeroff, 2010) . At this point, it is important to note that the neurotransmitter GABA plays an essential role in the modulation of the HPA-axis (Cullinan et al., 2008). There is also additional evidence from animal models, which illustrates how administration of stress-related hormones in rodents can produce pathological changes similar to MDD, which then can be treated by antidepressant administration (Warner-Schmidt & Duman, 2006; Dranovsky & Hen, 2006). Based on this evidence, the GABAergic deficit hypothesis proposes that MDD is caused by stress-induced deficits in GABAergic transmission and current monoaminergic antidepressants help the treatment of MDD by reversing the alterations caused in GABAergic transmission.

1.3 The GABAergic Deficit Theory of Major Depressive Disorder
Based on past research and GABAergic deficit theory of major depressive disorder (MDD), we believe it is important to examine GABA levels in depressed mothers and its effect on language acquisition. One of the most outstanding features of the human brain is its neuroplasticity. This feature refers to brain's ability to change throughout one's lifespan and adapt to new environments. Plasticity is also important for our cognitive functions such as learning, and language acquisition is no exception (Werker & Hensch, 2015). Although it has been shown that the human brain retains its plasticity over its lifespan, there are periods associated with increased plasticity named critical periods (CPs). After the onset of a CP, brain enters a higher-plastic state and stay in that state until the CP is closed (Hensch, 2016). There have been studies monitoring the onset and the offset of CPs in the brain and we have evidence that these timing can be modulated by neurotransmitter levels. For example, one study (Werker & Hensch, 2015) demonstrates how modulating the 5-HT levels via the administration of selective serotonin reuptake inhibitors (SSRI's) can increase cortical plasticity and shift the CP timing for infants' phoneme perception. Another study (Hensch, 2016) illustrates how GABA play a role in rodent visual system critical period timing.

  During CPs, increased plasticity is associated with increased firing rates of neurons and the pattern of neural firing can be considered as "random" or more chaotic, which allows new synaptic connections to be established between neurons. Although being in this state enhances our learning processes-any kind of learning can essentially be described as synaptic changes in the brain (Martinez & Matzel, 1996), the state itself is inherently unstable. The inhibitory effects exerted by GABA allow the pruning of weak synaptic connections, stabilization and preservation of the strongly potentiated connections, which establishes the neurobiological basis of learning as we know it. 

Figure 1: "A Young Brain's Window on the World" : a model of the critical period (CP). From "The Power of the Infant Brain" by Takao K. Hensch, 2016. doi:10.1038/scientificamerican0216-64. Copyright 2016 by Takao K. Hensch.



At this point, we think it is important to explain why we focus on GABA in particular. GABA is known to be a primary inhibitory neurotransmitter in the adult brain (Petroff, 2002), however, it acts as a primary excitatory neurotransmitter in the neonatal brain, including the embryonic period and first week of postnatal life, due to an inverted Cl- gradient in immature neurons. GABA-A(a type of  GABA receptor) is essentially a ligand-gated chloride channel and the function of GABA (i.e. whether it demonstrates excitatory or inhibitory properties) depends on the Cl- gradient. As neurons develop to maturity, the function of GABA shifts from being an excitatory neurotransmitter to inhibitory neurotransmitter and this shift coincides with the upregulation of expression of the KCC2(a K-Cl cotransporter), which eventually sets up the Cl- gradient as we know it (Ganguly et al., 2001; Leonzino et al., 2016). 

Considering both excitatory and inhibitory function of the GABA and its correlation with MDD, we propose that infants whose mothers were depressed during pregnancy would have a delayed shift both in onset and offset of CP timings for language acquisition.


METHODS
2.1 Neurobiological Experimental Design
Our subject sample will consist of 200 monolingual mothers residing in Canada, who will give birth via caesarean section. 100 of these mothers will be diagnosed with MDD and will not be getting any treatment or medication, while the other half will be non-depressed (control group).

To measure the GABA levels, we will take blood samples from umbilical cord right after the birth and examine the given sample via high performance liquid chromatography (HPLC). HPLC is a technique used in analytical chemistry that allows for the identification and distinguishability of different components within a solution.

Based on the GABAergic deficit theory of depression, we expect to record lower levels of GABA concentration in the samples we took from depressed mothers with the p< 0.05.

2.2 Family Assessments
For our proposed study, families who wish to be involved must provide consent to allow us to access their health information so that we may become aware of their medical background (e.g. physical health problems, history of mental disorders other than MDD, etc.). These families will be examined by psychiatrists in their homes through video/audio recordings for 7 days. Moreover, there will be joint interviews between family members and parental couples/single guardians, as well as personal, semi-structured interviews with family members. Observations made from the video/audio recordings and interviews will be used in conjunction with the Beavers-Timberlawn Family Evaluation Scale (BTFES) to establish an overall family functioning rating, which has 6 headings and 13 subscales that are rated according to a 5-point scale. For example, one heading is Family Affect, which includes the following subscales, directly taken from Grotevant & Carlson (1989): Range of Feelings (open, direct to no expression of feelings); Mood and Tone (warm, optimistic, humourous to cynical, hopeless, pessimistic); Unresolvable Conflict (severe to none); Empathy (consistent, empathic responsiveness to grossly inappropriate responses to feelings). Family functioning rating will be used to filter out families whose dynamics may introduce variability in identifying possible correlation between GABAergic deficits and language development.

There will be another phase to the family assessment for families who have passed the initial assessment, which will take place when the child is around four or five years old - three months prior to the third phase of linguistic assessments (the next section). The purpose of this secondary test is simply to follow-up on the participating families approximately three years after the initial family assessment, and to take note of any significant changes in family dynamics (e.g. loss of a loved one that may affect the family’s disposition, etc.) which may introduce variability in parental-child interactions or interactions between the child and other family members, which may ultimately affect language development.

2.3 Linguistic Assessments
According to the critical period (CP) model of perceptual development (Werker & Hensch, 2015), there are specific periods of plasticity that allow for the development of various aspects of language. Figure 1 suggests that the stages in language development affect subsequent stages, that is, such stages are key components of one or more successive stages. For example, at around eight months old, infants start to familiarize themselves with auditory (phonological) forms of words to which they are frequently exposed, and begin to store such words into their long-term memory (Juszyck and Hohne, 1997). Although the words do not have semantic value at this point, such word forms aid in future word learning, serving as a “foundation” upon which true words are built, after phonological categories have been established (as shown in Figure 2). It is through the eventual addition of grammatical and semantic information that word forms become true words, and are then added to the child’s vocabulary (Swingley, 2008).

Figure 2: Critical periods (solid lines) of the different stages (coloured boxes) in language development. Behaviour of critical periods - their opening, closing, and duration - are determined by sensory deprivation, pharmacological exposure, and experience in language (dashed lines). From “Critical Periods in Speech Perception: New Directions”, by Janet F. Werker and Takao K. Hensch, 2015, DOI:10.1146/annurev-psych-010814-015104. Copyright 2015 by Janet F. Werker and Takao K. Hensch.



Additionally, since there are specific durations (albeit subject to individual variability) for CPs at each stage, it is also suggested that a delay in one stage will delay the development in subsequent stages. With these in mind, we propose to assess the children’s progress in different stages of language development, specifically in the development of native phonetic categories, word forms, and language outcomes pertaining to phonological and grammatical awareness. Our testing periods will closely follow the duration of the critical periods as outlined in Figure 2, namely, the first two of three stages that were mentioned: native phonetic categories and word forms. Moreover, the testing period for the language outcomes stage will occur much after the above preliminary developmental stages, particularly, when the children reach the age of five.

2.3.1 Assessing native phonetic category development
When the infants are 13 months old, we will be assessing their ability to discriminate between native and non-native sounds using a “head turn” (HT) paradigm. The infants, after being conditioned to do so, will learn through positive reinforcement to turn away from a research assistant (RA 1) and to their left towards an animated toy (a dancing stuffed monkey) contained in a plexiglass box within a particular duration of time (4 s). The dancing toy will be illuminated only when a different sound is played among a sequence of repeating sounds. Another research assistant (RA 2) will be recording the responses on a smartphone.

2.3.1.1 Stimuli
We plan to use two sets of sounds. During the initial training period, we will be using /da/-/ta/, whereas for the testing phase, we will be presenting the English alveolar approximant /ra/ versus the Tagalog alveolar flapped /ɾa/.

2.3.1.2 Procedure
The experiment will take place in a room in which external sound is minimized. The infant will be sitting on their mother’s lap, opposite of RA 1 and RA 2. RA 1 will be holding a colourful toy so as to engage the child and to keep them looking at his or her direction. Both the mother and RA 1 will be wearing headphones so as to avoid influencing the child’s responses. After the unfamiliar sound is played, the RA 1 will discretely press a button to illuminate the plexiglass box and cause the stuffed monkey to move. (At this point, the control of the plexiglass and the stuffed monkey is on manual setting.) Once the child passes the conditioning phase - that is, once they make three HTs toward the toy in response to the sound change - then the researcher will press another button which will switch the control from manual to automatic (controlled by a logic system). During the testing phase, each HT will be recorded by RA 2 on a smartphone using the Noldus Pocket Observer.

Successful discrimination during the test phase will consist of 8 correct responses to the sound changes, with a maximum of three incorrect responses - misses or false positives. The criterion for a failed discrimination requires that the child pass the conditioning phase - that is, the child will need to be able to distinguish between /da/ and /ta/ - as well as less than eight correct responses and or more than three incorrect responses during the testing phase. This twofold aspect of the failed discrimination criterion is to ensure that the child indeed cannot discriminate between the native and non-native sounds and that the effects of external factors (e.g. fatigue, etc.) are eliminated or, at the very least, minimized. We will analyze if there is any correlation between successful discrimination and “normal” CPs (that is, within the bounds of the CP model in Figure 1), and failed discrimination and “normal” CPs.

2.3.2 Assessing interpretation of spoken words
When the infants are around 16 months, we will test their abilities to interpret spoken words by recording their eye movements through an audiovisual congruency test, in which they are asked by an automated voice recording to match the presented auditory information to the pair of visuals on a computer screen. This segment of the study will begin with a learning phase for Trial 1 words (LPT1), followed by a practice phase (PPT1), another learning phase but for Trial 2 words (LPT2), a practice phase (PPT2), and a threefold testing phase (TP1, TP2, and TP3, respectively). The learning phase is split into two instances so as to not bombard the infant with too much information in one sitting. The research assistant (RA) will be recording responses on an iPad using the same software as mentioned above (Pocket Observer), as well as facilitating the experiment, although most of the recording of data will be done by the eye tracker.

2.3.2.1 Words
The list of words that will be used in this part of the study are: apple, ball, dog, cat (T1W), and cow, sun, fish, and baby (T2W). These were chosen on the basis of level of difficulty and likelihood of recognition among children around this age.

2.3.2.2 Setup
The experiment will be held in a quiet, dark, enclosed room. Similar to the phonetic categories test, the child will be sitting on the mother’s lap, 30-60 cm away from a computer screen (Mac 21.5”). Underneath the computer screen will be a Tobii X120 eye tracker (Tobii Pro, Stockholm, Sweden), while a webcam in the computer will be recording the entire procedure. There will also be hidden speakers underneath the monitor of the computer. The mother will be wearing headphones and will be instructed to refrain from looking at the screen to avoid biasing the child’s response. Additionally, the mother will also be told to sit at a 90-degree angle from their child so that the eye tracker will only record the movement of the child’s eyes. The RA will be sitting approximately 60-90 cm from the mother and the child, recording observational data (e.g. head turns, change in reaction times, behaviour that may alter result, etc.) to supplement the data that will be recorded by both the eye tracker and the webcam.

2.3.2.3 Procedure
For both LPT1 and LPT2, the children will be presented the respective lists of words (i.e. T1W and T2W, respectively), individually, with their corresponding pictures. Upon visual presentation of the images, an audio recording will recite the corresponding word to such images. Each visual is presented once, while its matching word is said twice in an 8-second period: once during the first second, and another after 5 seconds. During both PPT1 and PPT2, the children will be presented two pairs of pictures from the set of words they have just learned, and will be asked to match the auditory information to the correct picture. For example, for PPT1, a child may be presented with a picture of an apple and a picture of a ball (both words are in T1W) on the computer screen, and an automated speaker may ask “Which one is the ball?”. Once the child makes 3 correct audiovisual matches on PPT1, he or she will then be able to move onto LPT2. If he or she makes 3 correct matches on PPT2, the child will then be able to move onto the testing phase.

The first part of the testing phase is similar to the practice phases, in which the child is presented with two pictures and are asked to match the correct picture to the information given through the verbal question, with the difference being that both T1W and T2W are used. To illustrate, a child may be presented with a picture of an apple (word from T1W) and a picture of a baby (word from T2W) on the computer screen, and an automated speaker may ask “Which one is the baby?”. The second part of this phase builds on this, but uses three pictures instead of two. Lastly, the final part of the testing phase will use mispronounced variations of the learned words. For instance, referring back to the hypothetical visual presentation of the apply and the baby, the prompt may ask “Which one is the vaby?”.

The criterion for successful interpretation of spoken words is that the child must make 4 correct responses out of 6 questions on the first substage, and 3 correct responses out of 6 questions on the second and third substages. For a child to be deemed unable to interpret the spoken words, he or she must pass both practice phases, pass the first substage of the testing phase, and subsequently fail the second substage of the testing phase. This is to ensure that we are able to distinguish the inability to interpret spoken words from factors such as boredom. We will examine if there is any correlation between successful interpretation and successful phonetic discrimination, successful interpretation and “normal” CP timing, as well as failed interpretation and failed phonetic discrimination, and failed interpretation and “normal” CP timing.

2.3.3 Assessing phonological and grammatical awareness
At around age 5, we will assess the children on their phonological and grammatical awareness using the backwards phoneme test and the wug test, respectively. The wug test is an oral test which assesses a child’s ability to apply English grammatical rules unto novel, nonsensical words. The test contains adjectives, verb conjugations, possessives, and the addition of -er to words (e.g. “A man who “fishes” is a fisher). The backwards phoneme test will entail one practice phase (B-PP) and two test phases (B-TP1 and B-TP2, respectively), while the wug test will comprise of one practice phase (W-PP1) and two test phases (W-TP1 and W-TP2, respectively). The list of words that will be administered in the backwards phoneme test will be taken from the MacArthur-Bates Communicative Development Inventory. The tests will be administered one after the other with one day in between, in the same setting, and will be facilitated by two RAs (RA 1 and RA 2). RA 1 will be mostly interacting with the child during the tests while RA 2 will be recording responses and or aiding RA 1 whenever needed. Unlike the two previous tests, this procedure does not require the child’s mother in the room. However, in extreme cases, exceptions may be applied depending on the child’s circumstance (e.g. child refuses to communicate with researchers without the presence of his or her mother). During these instances, special adjustments will take place to ensure that the mother does not bias the child’s responses - such as putting on headphones.

2.3.3.1 Setup
The two tests will take place in a quiet room that is attenuated to external stimuli (e.g. trees, sound, anything that can distract the child). As mentioned previously, RA 1 will be interacting with the child while RA 2 will be monitoring 30 cm behind the subject, and will be recording the responses on an iPad via Pocket Observer. RA 1 and the child participant will sit opposite from each other, 60-90 cm away from each other. There will be a video camera setup 90 cm away from the child to record the child as he or she progresses through the tests. For B-PP, the child will be given the following list of words: dog, cat, bat, bus, car, and toy. RA 1 will say each word then ask the child to repeat each word after. If the child is able to repeat 4 out of the 6 administered words, he or she will be ready to go into the testing phases.


2.3.3.2 Procedure (Backwards Phoneme Test)
During B-TP1 and B-TP2, the child will be required to say each word from a set list backwards. B-TP1 will be using the same set of words from B-PP. For example, a child may be asked to say dog backwards (in which they would say “god”). B-TP2 uses the same procedure, but the list of words is different: doll, bug, sheep, frog, book, and meat. Throughout this part of the study, RA 2 records the data and observations (e.g. Did the child have difficulty figuring out how to say dog backwards? Did they eventually achieve success in pronouncing the word? How long did it take?). The performance is not all-or-none, as response times can vary from child to child, depending on their age and vocabulary. If the child does indeed have difficulty with both phoneme test phases, several things will be considered. First, we will examine if there is any correlation between poor results on the phoneme tests versus the native sound discrimination tests, and any correlation between such results on the phoneme tests with the interpretation of spoken words assessment. Then, we will investigate if there is any correlation between such difficulties with their recorded GABA levels during infancy.

2.3.3.3 Setup (Wug Test)
Two days after the phonetic awareness assessment, the child will be tested, in the same room in which the phonetic test was conducted, for his or her grammatical awareness via the wug test. RA 1 will present the child pictures of fictitious characters from the wug test, such as in Figure 2, and the child will be expected to fill in the missing information that require them to apply English grammatical rules on those words. RA 1 will be reading to the child and asking them to fill in the information, while RA 2 will record observational data.

Figure 3: An excerpt from Jean Berko Gleason’s The Wug and Wug Test. http://blog.onbeing.org/post/12115178026/sunday-morning-exercise-take-the-wug-test. Copyright 2006 by Jean Berko Gleason.



2.3.3.4 Procedure
There will be a practice phase, W-PP, which entails applying grammatical rules to real English words (e.g. cat, dog, baby, etc.). For example, a child may be given the following scenario, accompanied with the corresponding picture/s of the subject (in this case, cats): “This is a CAT. Now there is another one. There are two of them. There are two _____.” (The expected answer is “CATS”.) The purpose of W-PP is for the researchers to gain an idea of the child’s level of grammatical awareness with everyday English words. Additionally, we will also use the performance on the W-PP to compare to the child’s performance on both test phases, W-TP1 and W-TP2. For instance, if a child does exceptionally well on W-PP but poorly on either (or both) W-TP1 and W-TP2 , there may be a possibility that the child has not internalized English grammatical rules to the extent that they are unable to generalize such rules and apply to any type of word - real or fictional (Swingley, 2000).

W-TP1 and W-TP2 will consist of progressing through the wug test. In analyzing the results of W-TP1 and W-TP2, performance will be graded, taking into consideration factors such as the level of difficulty that the child faced and with which aspects of the assessment he or she had difficulty (e.g. pluralizing a noun, etc.). Similar to the preceding analyses of the other tests, we will analyze if there is a correlation between i) performance on the wug test versus the performance on the interpretation of spoken words, ii) performance on the wug test versus performance on the native phonetic categories test, and iii) performance on the wug test versus GABA levels during infancy.

DISCUSSION
The structures and methods that we propose to implement in our study are heavily based on past literature that have yielded valuable results, especially in the area of psycholinguistics (Werker & Hensch, 2015; Swingley, 2008; Twomey et al., 2017). Thus, we feel that, with such knowledge and work available, it may be advantageous to use the latter as bases for a more comprehensive review on neurobiological implications on language outcomes among children.

3.1 The Need for Family Assessments
The need for family assessments stems from the belief that children’s progress in language acquisition is greatly influenced by family interactions at home (Beals & DeTemple, 1993), especially the quality of these interactions. Parents who are responsive to their children’s verbal initiatives and curiosity about their environment are more likely to have children with advanced language skills, phonological awareness, and comprehension skills (Tamis-LeMonda & Rodrigues, 2007). Given this, family interactions can serve as an external factor that may affect language development in young children, and deter from our goal of examining the effect of GABAergic deficit on language development. In addition, we acknowledge the considerable amount of time between the second and third linguistics tests (almost four years, to be exact), and so we propose to conduct another family assessment several months prior to the last linguistic assessment, so as to “touch base” with the participating families. Overall, the family assessments are implemented in an effort to minimize the effects of the children’s home environment.

3.2 Critical Periods, GABAergic levels, and Language Development
3.2.1 In relation to native vs. non-native phonetic sound discrimination
Young infants (6 to 8 months) can perceive contrasts between speech sounds, they can also perceive contrasts that are not distinctive in their parents’ language, which are difficult to discriminate for adults. By 10 to 12 months, infants lose this ability to perceive contrasts that are not distinctive in their own language (Werker & Tees, 1984). According to the CP model outlined by Werker & Hensch (2015), we predict that by this age, infants born from non-depressed mothers will stop discriminating, as a result of perceptual narrowing, while infants born from depressed mothers will still continue to discriminate. Although it can be argued that experience, such as exposure to words via listening, is determinant of the ability to distinguish native from non-native sounds, previous work suggests that experience simply “maintain[s] (or sharpen[s]) sensitivity” to distinctions in a native language, and reduce the discrimination for non-native sounds (Werker & Hensch, 2015). Given this, we anticipate that decreased GABA levels may delay the shift of CP so that children born from depressed mothers may still retain the ability to discriminate even when they are 13 months old.

3.2.2 In relation to interpretation of spoken words
In regards to the assessment of how infants interpret spoken words, it is likely that children with no CP delay will correctly identify the picture by matching the auditory information to the corresponding picture and maintain fixation upon it, whereas children with a delayed shift in CP may not correctly match pictures. This is primarily due to our theory, in accordance with the CP model by Werker and Hensch, that when CPs are delayed, perceptual development (in this case, the interpretation of word forms) may not be solidified; that is, extended CPs hinder perceptual narrowing such that the child is unable to retain understanding of or gain a knowledgeable grasp of the words they encounter. It is important to note, however, that children’s familiarization with words is not some process dependent on memorization. Indeed, existing literature speaks to the various heuristics children learn through auditory exposure to words, which they use to identify new words, such as grouping frequently-occuring syllables (Jusczyk, Houston, & Newsome, 1999) and changes in pitch and intonation (Seidl, 2007).

For the second part of assessing interpretation of infants’ spoken words (eg. doll), we believe that children would less readily recognize the word when it is mispronounced (“t”) and more readily recognize the word if it is well pronounced (“d”). But if children are unsure of the details of speech sounds in words, changing one sound to a similar one should not impair recognition (Swingley, 2000). Analysis of children’s eye movements conducted by Swingley (2000) showed that the time of fixation to the target picture was substantially reduced when the word was mispronounced (average 61%) relative to when it was correctly pronounced (73%). One might argue that vocabulary size is an influential factor as to a child’s sensitivity to mispronunciations, but studies have shown that there is a lack of correlation between the two (Swingley, 2000). Therefore, we hypothesize that the ability to grasp the interpretation of a word is dependent on perceptual narrowing.

3.2.3 In relation to phonological and grammatical awareness
For the backwards phoneme test, we expect that children of this age with normal language development, that is, without any history of speech disorders and or impairments, are able to distinguish the individual morphemes of each words. Thus, it is probable that children born from non-depressed mothers will be able to say the given list of words backwards with little to no difficulty, while children born from depressed mothers may find that it is a challenge for them to say the list of words backwards fluently. There are three stages of children morphological development, during the first stage children can memorize individual forms, when transferring to the second stage, they discover the morphological rules, which is then over-applied. As a result, they will gain mastery of exceptions on morphemes. The experimental evidence for children knowing morphological rules is the wug test (Rullmann, 2017). According to a previous study (Selby,1972) that had tested children’s morphological awareness via the wug test, we predict that children born from non-depressed mothers will have the ability to apply the rules of the English language on nonsense words while children born from depressed mothers whose CPs are thought to be delayed may consequentially have difficulties of applying such rules.

	However, the results correlated with GABA level of last two test may not as efficient as the other tests we mentioned above. It must be admitted that these two tests suffer from a limitation in the control of variables.  Since the children will be five years old at the time the backwards phoneme test and wug test will be performed, we cannot make sure that the difference of GABA level in placenta which in turn delay the critical periods is the only one possible reason that influence the development of language acquisition for children. There remain inevitable variables such as factors in family interactions like verbal stimulation through interactions with school-age siblings, which has been shown to affect reading abilities (Norman-Jackson, 1982), and genetic influences (Plomin & Dale, 2000) that may affect children’s language acquisition development.



CONCLUSION
Through an extensive and innumerable amount of consulted literature from various interdisciplinary fields, we believe that this project has widened our individual understanding of cognitive systems in more than one way. This project emphasized the importance of interdisciplinary communication, self-education, and big-picture thinking.

At the start of this collaboration, each member of the team, hailing from different areas of expertise - philosophy, psychology, and computer science, to be precise - aimed to simply “mediate” topics and or concepts from their respective fields to the rest of the group. For example, we heavily relied on team members with expansive knowledge on a certain field to relay their findings, while the rest of the group had little to no understanding of such findings whatsoever. We soon realized that this would not be able to bring forth a valuable research project, especially if we, individually, cannot recognize the value of past literature upon which we are to build the project. Simply put, we realized that each of us cannot cling onto our respective fields; we needed to be engaged in the other fields encompassed by our research project. As a result, we began to immerse ourselves in parsing through, and understanding, literature from other disciplines, and it was only then that we were able to raise questions (e.g. “How can we attribute delays in critical periods to GABAergic deficiency? Does this affect language development? If so, is it just in one stage or in multiple?”). However, in order to be able to gain understanding in a certain topic, one must be somewhat educated in the latter, in one way or another, and this project certainly reinforced such idea.

Interestingly, although this research project focuses copiously on psycholinguistics, we lacked a “linguistics” member - that is, we did not have a person with an extensive background on linguistics. At this point, we had two options: abandon the (very interesting) psycholinguistics topic of research and find a topic that is more catered towards our individual expertise, or push through with the idea and educate ourselves further with the little, or no, linguistic knowledge we had. Of course, we chose the latter, which proved to be more challenging and laborious, but academically and personally rewarding in the end. It was through educating ourselves that we were able to become more appreciative of how an infant’s environment, before and after birth, greatly influences their ability to acquire language - a mechanism that is often overlooked but is crucial to the functioning of every human being. Moreover, through immersing ourselves in linguistics, we were able to seek help from those knowledgeable in the field. We acknowledge the help of such people who were able to explain seemingly daunting concepts (e.g. examples of linguistics tests, measurements of word understanding, lexicon of linguistics, etc.) which, in turn, allowed us to delve deeper into the roots of language acquisition and infer its outcomes in preschool-aged children. Overall, it was through educating ourselves that we were able to extrapolate from literature and pose a bigger question of how language is affected in the long run.

Upon being able to communicate across disciplines and educating ourselves so that we were able to figure a means of conducting the research project, we were also inclined to think of the implications of executing the project, if that will ever be the case. We recognize that such a time-consuming project will require a considerable amount of manpower, not only pertaining to the vast array of researchers and professionals, but also the reliable amount of subjects, both mothers and children, over the estimated four years of observation. To compensate for the high attrition rates typical of longitudinal studies, we, as mentioned in a previous section, aim to recruit around 400 mothers and children across Canada. However, we predict that, even if we manage to gather such amount of participants, some may not pass the family assessments and, as such, will not be eligible to partake in our proposed research. In addition, we also anticipate the financial costs that will be introduced in executing such a longitudinal study, not only in providing compensation for the subjects, but also in acquiring different tools of measurement, and supporting the researchers and other professionals who are to be involved.

With all of this said, we remain confident that our proposed research will be of value to the pursuit of psycholinguistic knowledge. Through the assessments we have proposed to use in this particular study, we may be able to detect speech difficulties, especially those that may prove to be the early stages of speech disorders (Haiyou-Thomas et al., 2016). Moreover, we hope that our proposed comprehensive review of language development will further pave the exploration of the correlation between GABA deficiency and language development through early childhood, and we anticipate that future research will extend it one step further and identify if there truly is a causal link between the two.

BIBLIOGRAPHY

Albert, P. R., & Benkelfat, C. (2013). Introduction: The neurobiology of depression—revisiting the serotonin hypothesis. II. genetic, epigenetic and clinical studies. Philosophical Transactions: Biological Sciences, 368(1615), 1-4.

Albert, P. R., Benkelfat, C., & Descarries, L. (2012). Introduction: The neurobiology of depression—revisiting the serotonin hypothesis. I. cellular and molecular mechanisms.Philosophical Transactions: Biological Sciences, 367(1601), 2378-2381.

Beals, D.E., DeTemple, J.M. (1993). Home contributions to early language and literacy development. National Reading Conference Yearbook, 42, 207-215.

Bernard-Bonnin, A.C. (2004). Maternal depression and child development. Paediatr Child Health, 9(8), 575-583.

Bianchi MT, Haas KF, Macdonald RL. Alpha1 and alpha6 subunits specify distinct desensitization, deactivation and neurosteroid modulation of GABA(A) receptors containing the delta subunit. Neuropharmacology. 2002;43:492–502.

Binder EB, Nemeroff CB. The CRF system, stress, depression and anxiety insights from human genetic studies. Mol Psychiatry. 2010;15:574–588.

Cai, S., Fischer, Q. S., He, Y., Zhang, L., Liu, H., Daw, N. W., & Yang, Y. (2017). GABAB receptor-dependent bidirectional regulation of critical period ocular dominance plasticity in cats. Plos One, 12(6). doi:10.1371/journal.pone.0180162.

Charil, A., Laplante, D. P., Vaillancourt, C., & King, S. (2010). Prenatal stress and brain development. Brain Research Reviews, 65(1), 56-79. doi:10.1016/j.brainresrev.2010.06.002

Clement, J.P., Ozkan, E.D., Aceti, M., Miller, C.A., Rumbaugh, G. (2013). SYNGAP1 Links the Maturation Rate of Excitatory Synapses to the Duration of Critical-Period Synaptic Plasticity. Journal of Neuroscience, 33 (25) 10447-10452; DOI:10.1523/JNEUROSCI.0765-13.2013.

Cullinan, W. E., Herman, J. P. and Watson, S. J. (1993), Ventral subicular interaction with the hypothalamic paraventricular nucleus: Evidence for a relay in the bed nucleus of the stria terminalis. J. Comp. Neurol., 332: 1–20. doi:10.1002/cne.903320102

Cullinan, W.E., Ziegler, D.R. & Herman, J.P. Brain Struct Funct (2008) 213: 63. https://doi.org/10.1007/s00429-008-0192-2

Dranovsky A, Hen R. Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry. 2006;59:1136–1143.

Deidda, G., Allegra, M., Cerri, C., Naskar, S., Bony, G., Zunino, G., . . . Cancedda, L. (2014). Early depolarizing GABA controls critical-period plasticity in the rat visual cortex. Nature Neuroscience, 18(1), 87-96. doi:10.1038/nn.3890.

Erdö, S. L., László, A., Kiss, B., & Zsolnai, B. (1985). Presence of gamma-aminobutyric acid and its specific receptor binding sites in the human term placenta. Gynecologic and Obstetric Investigation, 20(4), 199.

Frodl T, Schaub A, Banac S, et al. Reduced hippocampal volume correlates with executive dysfunctioning in major depression. Journal of Psychiatry and Neuroscience. 2006;31(5):316-325.

Ganguly, K., Schinder, A. F., Wong, S. T., & Poo, M. (2001). GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition. Cell, 105(4), 521-532. doi:10.1016/S0092-8674(01)00341-5

Gerner RH, Hare TA. GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa. Am J Psychiatry. 1981;138:1098–1101.

Glynn, L. M., & Sandman, C. A. (2011). Prenatal Origins of Neurological Development. Current Directions in Psychological Science, 20(6), 384-389. doi:10.1177/0963721411422056.

Grovetant, H.D., Carlson, C.I. (1989). Family Assessment: A Guide to Methods and Measures. Guildford Press, 247-250.

Haiyou-Thomas, M.E., Caroll, J.M., Leavett, R., Hulme, C., Snowling, M.J. (2016). When does speech sound disorder matter for literacy? The role of disordered speech errors, co-occurring language impairment and family risk of of dyslexia. The Journal of Child Psychology and Psychiatry, 58(2), 197-205. doi: 10.1111/jcpp.12648.

Hensch, T.K. (2016). The Power of the Infant Brain. Scientific American, 314, 64-9.

Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord. 2001;62:77–91.

Jensen, J. E., deB. Frederick, B., & Renshaw, P. F. (2005). Grey and white matter GABA level differences in the human brain using two‐dimensional, J‐resolved spectroscopic imaging.NMR in Biomedicine, 18(8), 570-576. doi:10.1002/nbm.994

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(1), 60-99. doi:10.1016/0010-0285(89)90003-0

Jusczyk, P.W., Hohne, E.A. (1997). Infants’ memory for spoken words. Science, 1984-6.

Jusczyk, P.W., Houston, D.M., & Newsome, M. (1999). The beginnings of word segmentation in English-learning infants. Cognitive Psychology, 39, 159-207.

Kalueff, A. V., & Nutt, D. J. (2007). Role of GABA in anxiety and depression. Depression and Anxiety, 24(7), 495-517. doi:10.1002/da.20262.

Lenneberg, E. H. (1967). The Biological Foundations of Language. Hospital Practice, 2(12), 59-67. doi:10.1080/21548331.1967.11707799

Leonzino, M., Busnelli, M., Antonucci, F., Verderio, C., Mazzanti, M., & Chini, B. (2016). The timing of the excitatory-to-inhibitory GABA switch is regulated by the oxytocin receptor via KCC2. Cell Reports, 15(1), 96-103. doi:10.1016/j.celrep.2016.03.013

Llamzon, T.A. (1966). Tagalog Phonology. Anthropological Linguistics, 8(1), 30-9.

Luscher, B., Shen, Q., & Sahir, N. (2010). The GABAergic deficit hypothesis of major depressive disorder. Molecular Psychiatry, 16(4), 383-406. doi:10.1038/mp.2010.120

Lyon, G.R., Shaywitz, S.E., Shaywitz, B.A. (2003). A definition of dyslexia. Teachers’ Knowledge Of Language And Reading, 53(1), 1-14.

MacQueen, G. M. (2009). Magnetic resonance imaging and prediction of outcome in patients with major depressive disorder. Journal of Psychiatry & Neuroscience : JPN, 34(5), 343.

Martinez, J., J L, & Derrick, B. E. (1996). Long-term potentiation and learning. Annual Review of Psychology, 47(1), 173-203. doi:10.1146/annurev.psych.47.1.173

Mombereau, C., Kaupmann, K., Gassmann, M., Bettler, B., Putten, H. V., & Cryan, J. F. (2005). Altered anxiety and depression-related behaviour in mice lacking GABAB(2) receptor subunits. NeuroReport, 16(3), 307-310. doi:10.1097/00001756-200502280-00021

Nation, K., Hulme, C. (1997). Phonemic Segmentation, Not Onset-Rime Segmentation, Predicts Early Reading and Spelling Skills. Reading Research Quarterly, 32(2), 154-67. doi: 10.1598/RRQ.32.2.2.

Noldus: Pocket Observer. (2017). Retrieved from http://www.noldus.com/the-observer-xt/pocket-observer.

Norman-Jackson, J. (1982). Family Interactions, Language Development, and Primary Reading Achievement of Black Children in Families of Low Income. Child Development, 53(2), 349-58.

Olivier, J. D., Åkerud, H., Skalkidou, A., Kaihola, H., Sundström-Poromaa, I. (2015). The effects of antenatal depression and antidepressant treatment on placental gene expression. Frontiers in Cellular Neuroscience, 8. doi:10.3389/fncel.2014.00465.

Petroff, O. A. C. (2002). GABA and glutamate in the human brain. The Neuroscientist : A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 8(6), 562-573. doi:10.1177/1073858402238515

Petty F, Sherman AD. Plasma GABA levels in psychiatric illness. J Affect Disord. 1984;6:131–138.

Plomin, R., Dale, P.S. (2000). Genetics and early language development: A UK study of twins. In D. V. M. Bishop & L. B. Leonard (Eds.), Speech and language impairments in children: Causes, characteristics, intervention and outcome (pp. 35-51). New York: Psychology Press.

Quevedo, L. A., Silva, R. A., Godoy, R., Jansen, K., Matos, M. B., Pinheiro, K. A., & Pinheiro, R. T. (2011). The impact of maternal postpartum depression on the language development of children at 12 months. Child: Care, Health and Development, 38(3), 420-424. doi:10.1111/j.1365-2214.2011.01251.x

Rullman, H. (2017). LING 100: Introduction to Language and Linguistics, week 12 notes: Language and Culture [PDF]. Retrieved from https://ling100.sites.olt.ubc.ca/files/2017/11/100-2017W1-wk-12a-Language-and-Culture-print.pdf.

Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004;61:705–713.

Sapolsky RM, Krey LC, McEwen BS. Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci U S A. 1984;81:6174–6177.

Seidl, A. (2007). Infants’ use and weighting of prosodic cues in clause segmentation. Journal of Memory and Language, 57, 24-48.

Shah, P., Ebmeier, K., Glabus, M., & Goodwin, G. (1998). Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. controlled magnetic resonance imaging study. The British Journal of Psychiatry, 172(6), 527-532. doi:10.1192/bjp.172.6.527

Shen, Q., Fuchs, T., Sahir, N., Luscher, B. (2012). GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice. PLoS ONE 7(10): e47441.

Swan, D., Goswami, U. (1997). Phonological Awareness Deficits in Developmental Dyslexia and the Phonological Representations Hypothesis. Journal of Experimental Child Psychology. 66(1), 18-41. doi:10.1006/jecp.1997.2375.

Swingley, D., Aslin, R.N. (2000). Spoken word recognition and lexical representation in very young children. Cognition, 76(2), 147-66.

Swingley, D. (2008). The Roots of the Early Vocabulary in Infants’ Learning From Speech. Current Directions in Psychological Science, 17(5), 308-12.

Tamis-LeMonda, C.S., Rodriguez, E.T. (2009). Parents’ Role in Fostering Young Children’s Learning and Language Development. Encyclopedia on Early Childhood Development.

Tienari, P., Wynne, L.C., Sorri, A., Lahti, I., Läksy, K., Moring, J., Naarala, M., Nieminen, P., Wahlberg, K. (2004). Genotype-environment interaction in schizophrenia-spectrum disorder. The British Journal of Psychiatry, 184(3), 216-222. doi: 10.1192/bjp.184.3.216.

Tobii Pro: X3-120. (2017). Retrieved from https://www.tobiipro.com/product-listing/tobii-pro-x3-120/

Twomey, K.E., Ma, L., Westermann, G. (2017). All the Right Noises: Background Variability Helps Early Word Learning. Cognitive Science. doi:10.1111/cogs.12539.

Warner-Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16:239–249.

Werker, J. F., & Hensch, T. K. (2015). Critical periods in speech perception: New directions.Annual Review of Psychology, 66(1), 173-196. doi:10.1146/annurev-psych-010814-015104

Werker, J.F., Tees, R.C. (2002). Cross-language speech perception: Evidence for perceptual reorganization during the first year of life. Infant Behaviour and Development, 25(1), 121-33. doi:10.1016/S0163-6383(02)00093-0.

Wolf, M., Bowers, P.G. (2000). Naming-Speed Processes and Developmental Reading Disabilities: An Introduction to the Special Issue on the Double-Deficit Hypothesis. Journal of Learning Disabilities, 33(4), 322-4.