Review

Neonatal Transitions in Social Behavior and

Their Implications for Autism
Sarah Shultz,1,2,* Ami Klin,1,2,3 and Warren Jones1,2,3,*

Within the context of early infant–caregiver interaction, we review a series of Highlights

pivotal transitions that occur within the first 6 months of typical infancy, with From the first moments of life, neo-
nates exhibit a range of socially adap-
emphasis on behavior and brain mechanisms involved in preferential orienta-
tive preferences and reflex-like
tion towards, and interaction with, other people. Our goal in reviewing these responses that serve to orient their
transitions is to better understand how they may lay a necessary and/or attention towards caregivers, as well
as behaviors that serve as important
sufficient groundwork for subsequent phases of development, and also to signals to those caregivers.
understand how the breakdown thereof, when development is atypical and
those transitions become derailed, may instead yield disability. We review Within the first 6 months of typical
infancy, a series of pivotal transitions
these developmental processes in light of recent studies documenting dis- occur within the context of early infant–
ruptions to early-emerging brain and behavior mechanisms in infants later caregiver interaction, as initially spon-
taneous reflex-like responses transi-
diagnosed with autism spectrum disorder, shedding light on the brain–behavior
tion into remarkably sensitive and
pathogenesis of autism. contingent social action.

Neonatal Development in Context Recent reports suggest that these

At birth, the behavioral repertoire of human newborns is limited [1,2]. Within just days, weeks, developmental transitions may be dis-
rupted in autism spectrum disorder,
and months, however, early reflexes and reflex-like predispositions give way to complex opening a critical theoretical insight
volitional behavior: infants acquire new vocal abilities [3]; change their feeding, sleeping, into understanding the brain–behavior
and waking patterns [4–6]; and acquire new control of their eyes, neck, hands, and feet pathogenesis of autism.
[7–12]. Brain size at birth, approximately one-third that of an adult’s [13], doubles during the first
year [14] and increases by another 35% by year 3 [15]. Synaptic density quadruples in year 1
and will be 150–200% greater than that of an adult by year 3 [16,17] (to then be pruned or
selectively strengthened in iterations that continue throughout the lifespan [17,18]).

This enormous postnatal change, however, does not happen in a vacuum [19]; in the absence
of near-constant care, the infant’s survival would be nonviable [20,21]. The infant enters the
world in a state of utter fragility, and requires a parent or primary caregiver to provide for survival
needs. In playing that role, the caregiver serves as both partner and facilitator, matching his or
her own behavior (in facial affect [22,23], vocal tone [24,25], and physical touch [26,27]) to the
needs of the infant in a manner that serves as the foundation for further acquisition of abilities 1
Marcus Autism Center, Children’s
[27–29]. The behaviors of infant and caregiver are thus mutually adapted and mutually Healthcare of Atlanta, Atlanta, GA
reinforcing [30]: the infant–caregiver dyad, iteratively changing itself through interaction, is 30329, USA
2
Division of Autism and Related
an integral and inseparable unit of early development [31]. Disabilities, Department of Pediatrics,
Emory University School of Medicine,
Within that context, we review a series of pivotal transitions in the first 6 months of typical Atlanta, GA 30022, USA
3
Center for Translational Social
infancy that depend upon the mutually reinforcing context of the infant–caregiver dyad, with Neuroscience, Emory University,
emphasis on behavior and brain mechanisms thought to be involved in preferential orientation Atlanta, GA 30022, USA
towards, and interaction with, other people. This topic is especially timely given recent reports
demonstrating disruptions to early-emerging mechanisms of brain and behavior in infants later
*Correspondence:
diagnosed with autism spectrum disorder (ASD) [32–34], highlighting early periods of infancy as [email protected] (S. Shultz) and
key targets for future research. In reviewing this literature, we endeavored to link recent work to [email protected] (W. Jones).

452 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 https://doi.org/10.1016/j.tics.2018.02.012
© 2018 Published by Elsevier Ltd.
a broader set of seminal papers in neonatal behavior and development (additional references
can be found in online supplemental materials). Only by intensively studying these periods and
more fully understanding the growth trajectories that define normative development, will we be
able to gain new mechanistic insights into the pathogenesis of autism and related disabilities.

Mechanisms of Social Adaptive Action Present Shortly After Birth

The prolonged period of caregiver dependency and biological immaturity of human neonates,
lasting years longer than that of other primate species [35], has often been noted as a critical
aspect of human adaptive success [36]. More than simply providing a longer period of postnatal
plasticity in which to refine brain and behavior [37], the initial fragility and prolonged maturation
of the human newborn provide an ineluctable ‘initial task’ (that of survival) as well as a highly
specific context in which that task will be solved. That context, the specific setting in which
changes in newborn brain and behavior will take place, is defined by nearly continuous
interaction with other people.

Preferential Orientation and Reflexive Engagement

Shortly after birth, neonates already display remarkable attunement to their caregivers, dem-
onstrating reflexive and reflex-like patterns of behavior that enable close physical contact [38],
as well as distinct patterns of preferential orientation to the sights, sounds, and smells of their
caregivers [39,40] (preferences that are present already despite extremely limited ex utero
experience, with some preferences present already in utero [41]). These reflexive behaviors
increase an infant’s probability of initiating and/or maintaining direct caregiver interaction: the
palmar grasp reflex enables holding [38]; the Moro reflex facilitates caregiver contact in the
event of falling [42]; the rooting reflex aids neonates’ efforts to find mother’s nipple [9]; and the
sucking reflex facilitates successful and continued feeding [4].

In addition to the presence of these reflexive actions, rather remarkable preferences are evident
already at 10 minutes postpartum, when neonates will track a moving face-like pattern farther
than a pattern of scrambled or inverted facial features [43]. Similar evidence of preferential
orientation has been replicated within the first hour [44] and the first 1–5 days of life [45,46], for
cues ranging from biological motion [47] to others’ eyes [48]. These preferences are highly
specific (Figure 1), encompassing sight [48,49], sound [39], and smell [50,51] (touch, too,
undoubtedly plays a critical role [52,53] but remains relatively and unfortunately less well
studied).

Signaling Behaviors
In order to effectively increase the neonate’s chances of survival, the predispositions
described above must function as more than mere preference: viewed more broadly, these
predispositions must serve not only to direct neonatal resources towards the caregiver, but
also to elicit the response of those caregivers by serving as signaling behaviors [54]. Neonatal
crying is a clear example of a reflexive behavior that functions as a highly effective signal to
promote proximity and contact [55,56]. Crying reliably evokes perceptions of distress and
discomfort on the part of most parents [55], is associated with distinct patterns of brain
activity, and is believed to evoke distinct neuroendocrine responses (here the existing
literature is sparse in humans [57,58] but more well-established in animal models [57]).
Crying’s efficacy as a signaling behavior is also found in parents’ response: holding or
cuddling the infant is a highly efficient means of reducing or ending infants’ crying [59].
Crying thus signals the infants’ state but also elicits parent response and precipitates
additional opportunities for interaction.

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 453

 More preferred Less preferred
(A) Mother’s voice [39]
Stranger’s voice [39]
Complex non-speech [132]
Pure tone, structured noise [133, 134]
Silence [39]

(B)
Mother’s scent [51, 50]
Stranger’s scent [51, 50]

(C)
Mother, engaging [40, 45, 135, 136, 150]
Stranger, eyes open [48]
Stranger, eyes averted [48, 49]
Stranger, eyes closed [48, 49]

(D)

Biological moon [47]

Inverted bio moon [47]
Scrambled bio moon [47]

(E)
Face-like [43, 44, 45, 46, 94]
Face-like configural [43, 44, 45, 46, 94]
Face-like scrambled [43, 44, 45, 46]
Face-like inverted [43, 44, 45, 46, 94]

Figure 1. Neonatal Preferential Orientation to Caregiver Sounds, Smells, and Sights. Preferential orienting is observed already in the first days after birth in the
auditory domain (A), in response to olfactory cues (B), and in visual attention to faces (C), biological motion (D), and face-like stimuli (E). At 5 days, neonates show distinct
preference for looking at faces that have eyes open rather than closed and even distinguish, despite relatively poor visual acuity so soon after birth, between faces with
eyes directed towards them rather than away. Similarly, neonates distinguish and prefer their own mother’s voice to that of an unknown woman, but prefer the sound of
even an unknown woman’s voice to that of silence. In addition, neonates recognize their mother’s smell and will selectively head-turn at 2–7 days after birth towards the
scent of their own mother’s breast. Examples of more preferred stimuli are pictured in the left column while less preferred stimuli are pictured in the right column.
Stimulus descriptions and citations are given at far right. Data are from references [39,40,43–51,94,132–136,150].

Beyond the vocal domain, the neonate’s own facial musculature also serves as a potent
signaling system. Fully formed and functional at birth, neonates’ facial muscles enable them to
produce all but one of the discrete facial actions visible in adults [60]. Although these facial
expressions are not initially contingent upon caregiver behavior (e.g., neonatal smiles are largely
reflexive, occurring during sleep [61]), the muscle actions themselves clearly resemble inter-
pretable facial expressions, including smiling, brow-knitting, and pouting [60,62], and are fully
sufficient to evoke a caregiver’s emotional response. By evoking that response (without in any
way depending upon it), these noncontingent behaviors facilitate future (actually) contingent
social interaction [20,63].

454 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

The fact that initially spontaneous, noncontingent actions can beget actual social interaction
highlights a means by which adaptive solutions emerge from reoccurring couplings of infant
and caregiver [64]. In the preceding example, the capacity of the neonate (the physical ability to
form a smiling facial expression) combines with stable, recurrent features of the caregiving
environment (the consistency with which the caregiver responds to facial actions that look like
smiling). That coupling increases the joint probability of emergent social adaptive action,
beginning moments after birth. Critically, the neonate’s capacities and the functional signifi-
cance of those capacities as signaling behaviors cannot be understood without examining
them within the caregiving context into which neonates’ behaviors are adapted. Through
repeated interactions, solutions to the neonate’s initial task of survival lead to mutually adaptive
actions on the part of both neonate and caregiver.

Mutual Adaptation
The behaviors described above (behaviors that serve to preferentially orient neonates’ attention
towards their caregivers, as well as behaviors that then serve as signals to those caregivers) are
adaptive precisely because they provide selective advantage within an environment that
includes a caregiver. But those behaviors by themselves would not be sufficient for survival,
even in a caregiver’s presence. They require the reciprocal, complementary actions of the
caregiver, actions that are themselves modified to optimally respond to the signals of the
neonate and to then elicit further signals [20].

Evidence of this iterative mutual adaptation (Table 1) is found even upon first contact with the
neonate, when mothers display orderly and predictable patterns of species-specific behaviors
that include touch and an intense interest in establishing eye-to-eye contact [65]. The mother’s
interest in the neonate’s eyes matches the neonate’s ability to attend to mother’s eyes [48,49]
and appears to play an important role in establishing affective ties [65]. In addition to seeking
eye contact, caregivers use slow and exaggerated speech patterns, facial expressions, and
body movements that are well matched to the newborn’s restricted perceptual capacities
[20,66,67]. These are also the actions that appear to optimally engage young infants [66,68].

In another instance of parity between infant and caregiver, newborn crying elicits picking-up
and soothing [20], but newborn crying also occurs most frequently when newborns lose visual,
auditory, or physical contact with their caregivers [55]. Parental response thus serves to
reinstate that which was lost. Picking up the infant not only soothes and promotes state
regulation but also increases newborn arousal and visual attentiveness [20,59]. Likewise,
touching the infant has the effect of increasing infant eye contact with the caregiver [69]. Each
of these mutually adapted actions facilitates still further forms of interaction [70].

Caregivers are, of course, highly motivated to engage their newborns socially. Reflexive actions
of the newborn, such as grasping, are often interpreted by caregivers as signals of actual social
recognition, affection, or emotional expression, well before such actions are consciously
controlled or contingently deployed [20,63]. This perception creates rich opportunities for
newborn learning: the meaning that caregivers ascribe to newborns’ actions, and the way in
which caregivers then modify their own reactions accordingly, creates the ideal framework for
newborns to learn the meaning of their own actions: that is, through the reactions of their
caregivers [71,72].

Early patterns of imitative behavior reveal this exact form of interactional meaning-making.
Mothers imitate their babies’ gestures soon after birth and continue to increase their degree of
imitation in the following first 3 days [54]. Imitation is a form of mutual adaptation and another

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 455

Table 1. Mutual Adaptation of the Infant–Caregiver Dyad
Infant capacity/action Caregiver action/capacity Refs

Neonates have strong rooting and sucking reflexes. Rooting facilitates breastfeeding; sucking triggers maternal [9]
prolactin and oxytocin release (prolactin stimulates milk
synthesis and oxytocin produces milk release). Amount and
frequency of sucking determines the amount of breast milk
produced; without suckling, milk production ceases.

Neonatal sound production is limited (by state of vocal tract Crying reliably elicits caregiver actions, including closer [55,56]
development and brain maturation) to crying and vegetative physical proximity, increased holding, and increased
noises (sucking, sneezing, breathing). cuddling; in lactating women, infant crying stimulates blood
flow to the areolar area and milk flow from the breast.

Neonates significantly reduce their crying and become more caregivers provide proprioceptive-vestibular stimulation [59]
alert when . . . (holding and cuddling).

Neonates demonstrate varying states of alertness. Caregivers respond to periods of neonate alertness with [59]
affection: looking en face, smiling, talking, humming,
singing, cuddling, and kissing.

Infants are differentially sensitive to sounds encompassing Infant-directed speech (‘motherese’, with characteristically [68,146,147]
and modulated across a broader frequency range (150– exaggerated pitch contours) covers a broader frequency
550 Hz) than to sounds in narrower, lower frequency ranges range inclusive of higher frequency sounds.
(150–275 Hz) or to nonmodulated, lower frequency tones.

Newborns demonstrate increased responsiveness to voice Newborn responsiveness to voice sounds encourages [20]
sounds. caregiver interaction.

Neonates demonstrate differential neural processing of Sounds modulated over timescales of 25–50 ms are [148,149]
sounds modulated over timescales of 25–50 ms. particularly relevant for spoken communication.

The infant visual system has greater sensitivity to visual The faces and especially eyes of caregiving conspecifics [94]
signals with high-contrast polarity. contain multiple sources of high-contrast visual information.

The infant visual system has greater sensitivity to low (rather The faces of caregiving conspecifics are replete with low [81]
than high) spatial frequency information. spatial frequency information; facial affect cues are
communicated predominantly via low spatial frequencies.

Infants attend more to top-heavy, vertically asymmetric Human faces are vertically asymmetric with features [93]
patterns. concentrated in their upper portion; mothers display intense
interest in establishing eye contact with their infants.

Neonates spontaneously produce a broad range of facial Spontaneous facial expressions evoke emotional [20,60–62]
expressions and gestures. responses in caregivers, and caregivers imitate newborn
gestures which, in turn, increases infant gaze towards the
caregiver.

Infants produce voluntary, intentional facial gesturing. Caregivers respond to voluntary infant facial gesturing with [54]
‘modified imitation’: producing contingent responses or
producing different but related expressions; caregivers then
wait for infant to respond, initiating further cycles.

strong signaling behavior for both partners. Maternal imitation increases infants’ gazing
towards the mother, and an infant’s reflexive orienting towards the eyes of a caregiver reliably
elicits increased caregiver response [54,73].

Typical Transitions in Social Adaptive Action After 2–3 Months’ Experience

Neonates’ success in the social adaptive tasks described above (i.e., their success in prefer-
entially directing biological resources towards a caregiver; the success with which their
predispositions serve as signaling behaviors; and the success with which those signaling
behaviors then become mutually adapted to those of their caregivers) creates, in turn, a set of
new conditions that will further facilitate development. The initial acts of orienting, signaling, and

456 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

adapting establish myriad opportunities for extended social interaction. These new avenues for
social interaction present the infant with new tasks to be learned and put to use, setting the
stage for a cascade of transitions in behavior (Figure 2).

Early Adaptive Action Constrains Later Learning

The iterative process of early infant learning, whereby ‘each [ability] is first of all an effect of the
preceding [ability], and itself becomes the cause of the following [ability]’ ([74], p. 112), is well
illustrated by the learning that transpires in Rovee-Collier’s classic ‘infant conjugate reinforce-
ment’ paradigm [75]. In this experiment, an infant lies on her back, with a string connecting her
foot to a mobile that hangs above. Given the direct coupling between foot and mobile,
movements of the infant’s foot induce movement in the mobile, providing the child with novel

Percentage of infants who... Age (months)

>95% 0 1 2 3 4 5 6
Stare in a seemingly vacant manner -
- Vocalize predominantly by crying or making small throaty noises
80% Stare fixedly at windows or walls when lying on their backs -
- Exhibit clear signs of forearm muscle recoil
Exhibit a clear Moro reflex -
65% - Ehen lying on back, keep their heads predominantly in a rotated posi on
Keep their arms predominantly in the asymmetric tonic neck reflex posi on -
50% - Exhibit a clear Palmar grasp reflex elicited by index finger
Exhibit a clear Babinski reflex -
- Exhibit a clear toe grasp reflex
35% When lying on their backs, move their arms and legs equally well -
- Respond clearly to the sound of a bell
Look at and regard others' faces when lying on their backs -
20% - Vocalize by making cooing and other non-cry sounds (‘uh’, ‘eh’)
Follow a moving object with their head and eyes to the midline -
- Turn their heads from side to side when lying on their backs
<5% Li their heads up 45° when lying on their stomachs -
- Follow a moving object with their head and eyes past the midline
Vocalize by making vowel sounds such as ‘ooo’ and ‘aah’ -
- Smile reciprocally with a caregiver
Follow a moving object from le to right and from top to bo om -
- Vocalize by making laughing sounds
Li their heads up 90° when lying on their stomachs -
- Can hold their heads steady when si ng
Look at and inten onally regard their own hands -
- Vocalize by making sounds in response to a caregiver's a en on
Can hold their heads steady when held standing -
- Can support some weight on their legs when held standing
Follow an object moving in a circle (in upper and lower quadrants) -
- Bring their hands together
Increase their arm movements when presented with a dangling ring -
- Can roll over from stomach to back or from back to stomach
Sober at the presence of strangers -
- Play with their hands by touching them together
Hold their heads up erect and steady, without support, when picked up -
- Express mul ple clearly differen ated emo ons in response to external events
Can pull themselves up to a si ng posi on when their hands are grasped -
- Succeed in reaching and contac ng a dangling ring
Use their arms to support upper body weight when lying on their stomachs -
- Show no signs of head lag when pulled to a si ng posi on
Clearly coordinate eye–hand ac on by seeing and reaching for objects -
- Hold their hands open (rather than clenched) when not otherwise engaged
Can successfully reach and grasp a ra le when presented -
- Vocalize by imita ng speech sounds
Can rotate their wrists from palm up to palm down when holding an object -
- Work for out-of-reach objects, stretching their arms or their bodies
Can support their whole weight on their legs when held standing by the hands -
- Explore objects placed in their hands
Make appropriate reciprocal gestures to show that other's gestures are understood -
- Can pick up a block using one or both hands
Vocalize by making single syllables such as ‘da’, ‘ba’, ‘ga’, or ‘ma’ -
- Li their arms to express a desire to be picked up
Can use a pincer grasp, with pad of thumb and any finger p, to grasp an object -
- Vocalize by babbling when they play alone
Can transfer a block from one hand to another -
- Vocalize by making non-specific ‘dada’ or ‘mama’ sounds
Can move to a si ng posi on without a caregiver's aid -
- Try to grab an object from the caregiver's hand
Vocalize by making ‘mama’ or ‘dada’ sounds, specific to mother or father -
- Play peek-a-boo
Wave good-bye in response to another person -
0 1 2 3 4 5 6
Age (months)

Figure 2. Developmental Milestones in Infants’ First 6 Months. Plotted data, showing the percentage of infants who display each listed behavior between birth
and 6 months. Behaviors are plotted sequentially, with behaviors that emerge (and, in some cases, decline) earlier in development at the top and behaviors emerging
later in development at the bottom. This sequence of developmental milestones highlights the cascading process of infant development, whereby an infant’s own
emerging abilities lead the infant towards new ways of exploring and experiencing the world, prompting further development in an iterative process. Developmental
milestone data were scanned or transcribed from published texts and manuals [8,10,12,137–142]; data were fitted with a sigmoid function to describe the cumulative
proportion of children displaying each behavior (common milestones were averaged across sources). The fitted functions are color-scaled from generally absent (black)
to present in 50% of children (red) to present in most children (yellow).

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 457

reinforcement of what were initially only spontaneous leg movements. Importantly, infants
discover this relationship themselves: as infants spontaneously kick their feet they learn the
contingency between their own movements and the movement of the mobile. Once this link is
discovered, the act of kicking, initially spontaneous and unrelated to the mobile, acquires new
meaning: kicking becomes an instrumental act for effecting control over the external world. As a
consequence of this newfound adaptive value, more precise and vigorous instrumental kicks
increase while spontaneous and undirected kicks decline [76].

These data illustrate two key points about developmental change. First, infants play an active
role in discovering their own new tasks: in this case, they discover a direct but previously
unknown link between their own actions and those of the external world, and they then learn to
control and exploit that link. Second, learned volitional behaviors can emerge from and/or
depend upon behaviors that were initially spontaneous or reflexive.

Together, these two points demonstrate highly specific constraints that specify and guide
subsequent skill acquisition: both the spontaneous initial actions (kicking rather than, for
example, hand-waving) as well as the learned solution to that task (kicking with specific
magnitude and direction) have the direct effect of limiting and specifying future instances
of, and opportunities for, learning. If no initial kicks occurred, or the relationship between kicking
and mobile never discerned, the contingency would not be learned. Likewise, by learning to
control the mobile with specific kinds of kicks, the probability of other actions (e.g., trying to use
hand-waving for the same purpose) declines, while the probability of the newly learned kicking
increases (see [77] for an additional elegant example of how early experiences precipitate
changes in infants’ subsequent activities).

In short: by selectively exploiting specific actions that successfully yielded past adaptive results,
infants transform not only their own future behaviors but also their own future possibility of
behaviors (i.e., altering the probability that other related behaviors will be more or less likely to
occur) [78].

Reflex-like Behaviors Give Way to Volitional Actions

The kicking-to-mobile-movement contingency is by no means the only case in which learned,
volitional behaviors replace, emerge from, and/or depend upon behaviors that were initially
spontaneous or reflexive. A host of such transitions occur in a variety of different developmental
domains in an infant’s first months (Figure 3).

For instance, the side-to-side head turning reflex, a variant of the rooting reflex, is thought to
play an important role in feeding by providing an opportunity for the neonate’s mouth to come
into contact with the mother’s nipple [9]. As neonates gain increasing experience with feeding,
this initially spontaneous action transitions to a directed head turning reflex at approximately 2–
3 weeks of age [4,9], and then transitions again to volitional directed head turning at approxi-
mately 3 months [11]. The hand grasping reflex, present at birth, begins to disappear at
approximately 4–5 months of age, coinciding with the emergence of voluntary reaching and
grasping [38]. Similarly, the toe grasping reflex, also present at birth, begins to fade as infants
gain voluntary control over feet and legs and begin to crawl [10].

These transitions from reflexive behaviors to volitional actions do not appear to progress
according to lockstep chronological timers; instead, they depend more heavily on individualized
experiences that are necessary to facilitate later transitions. For instance, the directed head
turning reflex persists longer in infants who are breast-fed compared with infants who are

458 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

(A) Reflexive crying
Vowel sounds (‘ooo’, ‘aah’)
>95
75 Sounds in response to aƩenƟon
% of children

50 Consonant sounds (‘m’, ‘b’) (C) Reflexive eye-looking

VoliƟonal, social-
25 ‘Mama’ or ‘dada’
50 interacƟona l eye-looking
<5
0 1 2 3 4 5 6

% fixaƟon on eyes
Chronological age (months)
Reflex-like tracking 25
Follow object leŌ–right,
>95 top–boƩom
75
% of children

Follow object in circle 0

50 0 2 4 6 8
25 Chronological age (months)
<5
0 1 2 3 4 5 6
(D) TD
Chronological age (months) Hypothesized Observed
50
Arms in ATNR posiƟon
Increase arm movements VoliƟonal

% fixaƟon on eyes
>95 when presented with ring
75
% of children

Reach and grasp raƩle 25

50
Pick up block
25 Reflexive
<5 Wave good-bye
0
0 1 2 3 4 5 6 0 2 4 6 8
Chronological age (months) Chronological age (months)

Palmar grasp reflex

>95 Holds hands open ASD
75 rather than closed Hypothesized Observed
% of children

50
50 Uses pincer grasp
% fixaƟon on eyes
25
<5 Reflexive
25
0 1 2 3 4 5 6
Chronological age (months)
(B) VoliƟonal
Reflex-like acƟons 0
>95 0 2 4 6 8
75 VoliƟonal behaviors Chronological age (months)
% of children

50
25 Hypothesized Observed TD
<5 50
0 1 2 3 4 5 6
% fixaƟon on eyes

Chronological age (months)

25 ASD
Reflex-like acƟons
AdapƟve value

VoliƟonal behaviors

0
0 2 4 6 8
Chronological age (months)

Normalized developmental Ɵme

Figure 3. Transitions from Reflex-like Actions to Volitional Behaviors. Behavioral transitions in the first 6 months of life, with implications for early social behavior
in autism. (A) Data from references [8,10,12,137–142] showing examples of declining reflex-like actions (unbroken lines) and emerging volitional behaviors (broken lines)
in the vocal, visual, and motor domains. Approximate transition times are marked by vertical lines. (B) Top, trajectories of reflex-like actions and volitional behaviors from
(A) are plotted against chronological age. Bottom, trajectories are aligned at the time of transition to illustrate the idea that learned, volitional behaviors may replace,
emerge from, and/or depend upon behaviors that were initially spontaneous or reflexive: as new volitional behaviors are acquired, the adaptive value of simpler reflex-like
actions decreases, as does the action. (C) In typical face perception, existing normative data [44,45,81,92] suggest a similar transition at approximately 2 months: reflex-
like eye-looking declines (unbroken gray line) while volitional eye-looking increases (broken gray line). Reflexive eye-looking is believed to be experience-expectant and
subcortically mediated, while volitional eye-looking is believed to be experience-dependent and largely cortically mediated. (D) A corresponding reduction in amount of
eye-looking by typically developing (TD) infants has been observed at the hypothesized time of transition, shown in the top panel (blue line, sum of percentage fixation on
eyes). Observed data from months 2–8 replotted from [32]. Trajectories from 0–2 months represent hypothesized levels of eye-looking in keeping with existing normative
data [96,97]. In observed data from [32], infants with autism spectrum disorder (ASD) exhibited relatively high levels of eye-looking at 2 months, which then declined. By
contrast, TD infants showed relatively low levels of eye-looking at 2 months, which then increased. Relatively high levels of eye-looking at 2 months in ASD (red) suggests
reflex-like eye-looking that is not supplanted by volitional eye-looking and, instead, persists atypically. Rather than an outright failure of cortically controlled voluntary
preferential attention in ASD, eye-tracking data suggest a co-opting of experience-dependent cortical mechanisms by attention to other, nonsocial features in the
environment. As a result, reflex-like eye-looking gradually declines as it is supplanted by attention to other (non-eye) features. Abbreviation: ATNR, asymmetrical tonic
neck reflex.

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 459

bottle-fed [4]; voluntary reaching and grasping emerge earlier in infants who are afforded the
experience of picking up objects [77]; and the decline of the toe grasping reflex is more closely
related to the acquisition of voluntary control of the feet than to chronological age [10]. Each of
these examples can be thought of as an individualized timescale of development: initial
behaviors provide pivotal opportunities that enable subsequent learning, in highly individualized
fashion. (For more on individualized timescales of development, and recent statistical advances
in the measurement thereof, see Figure 4.)

(A) (B)
200
Individual differences in...
180
Timing Scale Timing and scale
160

140
Height (cm)

Height

Height

Height
120

100
Individual height measurements,
80 for 54 girls, measured at 31 Ɵme
Chronological age Chronological age Chronological age
points between year 1 and year 18.
60

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Chronological age (years)

Linear modeling Func onal data analysis

(C) Power Polynomial, 5th order (D) B spline (E) (F) Registered funcƟonal data

Warping funcƟons
Height

Height

Height
17
Faster than
MaturaƟonal age (years)

14 average

Chronological age (years) Chronological age (years) Chronological age (years) MaturaƟonal age (years)
11

8
in height

in height

in height
Change

Change

Change

5 Slower than
0 0 0 average
0

Chronological age (years) Chronological age (years) Chronological age (years) 2 MaturaƟonal age (years)
Rate of change

2 5 8 11 14 17
Rate of change

Rate of change
in height

in height

in height

Chronological age (years)

0 0 0 0

2 5 8 11 14 17 2 5 8 11 14 17 2 5 8 11 14 17 2 5 8 11 14 17

Chronological age (years) Chronological age (years) Chronological age (years) MaturaƟonal age (years)

Figure 4. Developmental Methods: Quantifying Individualized Timescales of Growth. Functional data analysis is a relatively new method of analyzing time
series data that places greater emphasis on individual trajectories of data, considering the trajectory itself to be a single observation and quantifying that function’s
variability in terms of both timing and scale [143,144]. This is an important methodological as well as conceptual shift in how longitudinal data are analyzed and
understood, with exciting implications for studies of child development and for the conclusions we may draw about underlying biological processes. A good example of
this shift can be seen when analyzing a very literal example of a child’s growth: change in height. (A) Shows height measurements of girls from 1 to 18 years of age (from
the classic Berkeley Growth Study [145]). The underlying biological process of growth is of course nearly identical in all children, but exactly when the pubertal growth
spurt occurs and how large it is varies considerably by individual. (B) Individual differences can be expected in timing (when a particular change occurs), in scale (how
large or small a given change may be), and in both timing and scale. With conventional growth curve modeling, (C) fitting individual data with a power function (left panels)
yields a relatively good fit in statistical terms (R2 > 0.98 for each of the three example curves); however, it also eradicates all signs of the pubertal growth spurt, as seen
especially in the plots of change in height and in rate of change in height (the 1st and 2nd derivatives, respectively). Fitting the same data with a 5th order polynomial [right
panels of (C)] improves the picture somewhat, but parameter estimates of when the pubertal spurt occurs in individual children (colored dots) are as much as 2 years
earlier than estimates observed in a more data-driven fashion, as in (D), using B-spline basis functions. (D) In functional data analysis, variation in both timing and scale
are quantified, and curve shape is determined empirically. (E) Rather than being confounded by individual differences in maturational rate (individualized developmental
timescale), functional data analysis measures the extent of these differences as ‘warping’ or registration functions, explicitly comparing and correcting for differences in
chronological time versus individual maturational time. (F) When data are analyzed as functional trajectories, registered according to measures of individual difference in
developmental timing, the ability to estimate the shape of the actual developmental process improves substantially.

460 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

Infant–Caregiver Adaptation Guides Developmental Transitions
The developmental learning processes described above are equally applicable to transitions in
social learning. Just as infants discover a physical linkage in the foot and mobile example,
infants also discover links connecting them to their social partners [79,80]. Research on infant–
caregiver dyads reveals that infants’ facial movements, head movements, and vocalizations are
coupled, often tightly, to the facial expressions and sounds of their caregivers [54,79]. As infants
discover and exploit the links between their own actions and the actions and reactions of
others, the spontaneous and reflex-like behaviors of the neonate are transformed.

One notable example of such a transition is the case of orienting towards faces. Preferential
tracking of faces (as described above) is initially a reflex-like, spontaneous, stimulus-driven form
of orienting, observed from the first hours after birth [43]. Notably, however, this neonatal
orienting response declines after 4–6 weeks postpartum, reaching a relative low point, before
preferential attention to faces then increases at approximately 2 months [29,81]. This would
appear to be a transition from a more reflex-like response (i.e., not socially contingent) to a more
volitional, truly social, form of orienting. Evidence of this transition is also supported by other
changes at approximately 2 months. First, the physical characteristics of face-like stimuli that
most effectively elicit preferential attention also change: while neonatal preference for faces can
be elicited by simple schematic stimuli [44], real faces are preferred by 1–2-month-old and older
infants (reviewed in [82,83]).

In addition, the 2nd month also marks the first time in which clear evidence exists that infants
engage with other people in an interactive, socially meaningful manner. At approximately 2
months, infants begin smiling and cooing in response to faces [84]. Prior to this point, neonatal
smiling is endogenous, happens most often during sleep, and shows little evidence of linkage to
external stimulation [61,84]. At 2 months, however, smiles begin to be contingently linked to
changes in caregiver vocalization and affective state, indicating not only the emergence of
social smiling but also indicating that infants’ preferential visual attention (in this case, directed
towards faces) now also functions as a form of communication [84]. Newborn vocal develop-
ment also undergoes marked change shortly thereafter: prior to approximately 3 months,
crying is reflexive, undifferentiated, and marked by an absence of vowel production; after 3
months, cries become interactive, intentional [85], and increasingly reflective of the infant’s
psychophysiological state [3] (note that the timing of these changes, in contrast to smiling, is
partially constrained by anatomy: at 3 months, the larynx descends [3] and the ribs reconfigure
[86], altering the infant’s capacity for vocal production).

Finally, there are also large changes at approximately 2 months in infants’ expectations of other
people. New capacities for active social engagement are evidenced by several classic studies:
in the still-face paradigm [87], when a formerly interactive partner becomes unresponsive, 1.5-
and 3-month-old infants (but not neonates) become upset, with signs of distress including
crying, general negative affect, and shifts in visual attention away from the caregiver [88]. In
addition, infant social bids during the still-face phase increase at 2 months of age [80], offering
evidence that infants have now become active agents in dyadic interaction, developing specific
expectations of the ways in which social interactions should unfold.

As infants exploit the links between their own actions and those of their caregivers, caregivers,
in turn, modify their behavior to progressively advance cycles of learning. During the infant’s
second month, mothers spend more time talking and smiling with their infants, and less time
displaying neutral facial expressions [89]. Regularities in face-to-face play (such as turn-taking)
are established, repeated, and then extended during this period [54], with the peak in face-to-

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 461

face play occurring between 3 and 6 months [90]. Evidence suggests that mothers of 3-month-
olds display an average of approximately eight changes in emotion-related facial expressions
per minute [54]. With even 3 hours per day of direct interaction, and with as little as 25% of that
time spent directly attending to mother’s face [91], an infant would be exposed to approxi-
mately 360 changing emotional cues in a single day, or more than 32 000 between the ages of 3
and 6 months.

Co-occurring Changes in Early Infant Brain and Body Systems

Relative to our knowledge of infant behavioral transitions, detailed information about co-
occurring changes in brain are still limited. Existing knowledge does, however, suggest a
substantial transition also occurring at approximately 2 months, shifting from largely subcortical
to increasingly cortical control [92].

At birth, reflexive visual orienting appears to be supported by the subcortical visual system,
which is differentially responsive to low-spatial frequency information [81], top-heavy vertically
asymmetric patterns [93], and high contrast polarity [94]. Notably, these are all properties also
strongly represented in the faces and eyes of conspecifics, and much like other mutual
adaptations between infant and caregiver (Table 1), this match between signal and receiver
may be a means of increasing the probability that neonates orient towards conspecifics rather
than other competing stimuli [81,95].

As the neonate enters her second postnatal month, existing models suggest that reflexive
orienting responses, subserved by subcortical structures, decline due to developing inhibition
by cortical circuits (as visual preferences come under increasing cortical control) [96]. This
theory is supported by the relative immaturity of primary visual cortex at birth [97] and also by
developmental changes in orienting. Newborn orienting is most effectively elicited by face-like
stimuli presented in the peripheral visual field [45] (the area that feeds more directly into
subcortical visual pathways [98]), whereas preferential orienting in 2-month-olds is more
effectively elicited by stimuli presented in the central visual field (which feeds more directly
into cortical visual pathways [97]). Further evidence comes from the fact that retinocortical
pathways become fully functional at approximately 2 months [99], and signs of adult-like
cortical specialization for face processing are also first observed at 2- to 3-months in both
event-related potential (ERP) [100] and positron emission tomography studies [101].

Generally speaking, however, much is still to be learned about infant brain development and the
manner in which behavioral milestones are coupled with brain changes. Newly available
resources (e.g., the Allen Human Brain Atlas [102] and BrainSpan [103,104] projects) and
ongoing projects (Human Connectome [105] and Developing Human Connectome [106]
Projects) are likely to transform our understanding of infant brain development in the coming
years (Figure 5). Currently, however, data from infant behavior and brain development show-
case a system that undergoes enormous developmental change in a matter of months:
neonatal preferences and reflex-like responding give way to remarkably sensitive and contin-
gent volitional action. We now review some of the emerging literature regarding what is currently
known about the derailment of such action in children with ASD.

Disruptions in Social Adaptive Action in Autism Spectrum Disorder

A striking developmental contrast in autism is that older children, and even adults, on the autism
spectrum often exhibit deficits in social adaptive action that are otherwise present in typical
infancy. For example, while typically developing infants preferentially orient to the eyes of others
[48,49], 2-year-olds [107], 10-year-olds [108], and even adults [109] with ASD do not.

462 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

 DLPFC
(A) M1/S1 (C)
% of maximum
IPC
STG
Longitudinal expression of genes associated with... expression level

V1 Neurogenesis 0% 50% 100%

THAL -
- STR
AMG -
VLPFC - HIP
M1/S1 -
OFC - VLPFC
STG -
-CB
ITC OFC -
CB - DLPFC
IPC -
THAL - ITC
MPFC -
- V1
0 1 2 3 4 5 6 9 12 15 18 24
Age (months)
Synaptogenesis
MPFC -
- THAL
HIP -
- STR
V1 -
-CB
MPFC IPC -
STR - ITC
M1/S1 -
AMG - OF C
HIP DLPFC -
- STG
VLPFC -
- AMG
AMG Amygdala 0 1 2 3 4 5 6 9 12 15 18 24
CB Cerebellum Age (months)
DLPFC Dorsolateral prefrontal cortex Dendrite development
V1 -
HIP Hippocampus - THAL
HIP -
IPC Inferior parietal cortex - STR
VLPFC -
ITC Inferior temporal cortex - AMG
ITC -
- IP C
M1/S1 Primary motor & primary M1/S1 -
- STG
somatosensory cortex MPFC -
-CB
MPFC Medial prefrontal cortex DLPFC -
- OFC
OFC Orbital frontal cortex 0 1 2 3 4 5 6 9 12 15 18 24
STG Superior temporal gyrus Age (months)
STR Striatum Axon development
THAL -
THAL Thalamus - STR
HIP -
V1 Primary visual cortex VLPFC -
- AMG
VLPFC Ventrolateral prefrontal cortex - M1/S1
V1 -
- STG
IPC -
- MPFC
OFC -
(B) ITC -
- DLPFC
-CB
Neurogenesis
0 1 2 3 4 5 6 9 12 15 18 24
DCX Age (months)
Synaptogenesis SYP, Myelinaon
THAL -
SYPL1, SYPL2, SYN1 -CB
STR -
Dendrite development MAP1A, AMG -
- M1/S1
MAPT, CAMK2A VLPFC -
- HIP
- STG
Axon development IPC -
- V1
CNTN2 MPFC -
- ITC
OFC -
Myelinaon C11orf9, MAG, - DLPFC
MBP, MOG, PLP1 0 1 2 3 4 5 6 9 12 15 18 24
Age (months)

Figure 5. Longitudinal Expression of Genes Associated With Neurodevelopmental Processes. Recent advances in studying the spatio-temporal dynamics
of gene expression in the human brain augur a new frontier for studies of infant and child development, connecting well-studied behavioral and cognitive milestones to
multiple measures of infant brain biology. One example is the BrainSpan Atlas of the Developing Human Braini [104], offering a transcriptional architecture of the human
brain from early fetal development through adulthood. While longitudinal expression patterns for more than 17,500 genes were analyzed, the gene expression
trajectories plotted here are for genes whose differential expression is associated with key neurodevelopmental processes. (A) Fourteen brain regions in which
expression was measured are highlighted. (B) Five sets of genes are highlighted, the expression levels of which are associated with neurogenesis, synaptogenesis,
dendrite development, axon development, and myelination, respectively. (C) Longitudinal expression levels of genes associated with each process are plotted, for each
brain region, as a percentage of the minimum and maximum lifetime levels of expression. Brain regions are sorted according to peak expression levels between 0 and 24
postnatal months of age. Note the clear waves of expression during these periods of early child development: high levels of expression associated with neurogenesis
continue through the first 6 months of life, with marked decline thereafter, followed by waves of increased expression associated with synaptogenesis, dendrite
development, axon development, and finally myelination. Given the enormous developmental change occurring in these time periods, data like these, coupled with
densely sampled behavioral and neuroimaging data, are likely to transform understanding of infant development in the coming years. See online supplemental materials
for additional related references.

Unfortunately, direct observation of infant development in autism is still limited. Given the late
average age of conventional diagnosis [110], and the extent to which diagnosis currently
depends upon behaviors that emerge in toddlerhood [111], a large gap in current knowledge
remains. To fill that gap, the past 10 years have seen a substantial increase in prospective

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 463

studies of the infant siblings of children with ASD, whose risk of also having the condition is
approximately 20% [112], a substantial increase relative to infants in the general population
[113].

Social Adaptive Action and Brain Specialization in Autism Spectrum Disorder

Recent studies examining the course of early social development in high-risk infant siblings
have focused primarily on measures of social attention, interaction, and/or more general
aspects of social development, using standardized assessments as well as experimental tasks
(see online supplemental materials for references). A wide array of between-group differences
have been identified among infants subsequently diagnosed with ASD, including, among
others, differences in frequency of shared smiles, vocalizations, and gaze to faces
[114,115]; attention to social scenes and images [116]; attention to and engagement with
objects [117]; ERP amplitude differences in relation to observed eye gaze [118]; temperament
profiles [119]; responsiveness to distress in others [120]; mutuality of infant–caregiver interac-
tion [121]; and social smiling and joint attention [122,123].

Related differences are also found in brain structure [34,124,125] and function [33], with
differences in extra-axial cerebrospinal fluid volume [125], cortical surface area [34], white
matter fiber tracts [124], and functional connectivity [33] all identified as possible predictors of
autism in the first year of life. Some studies have also highlighted ways in which similar overt
behaviors were accompanied by notable differences in measures of underlying brain function
[118,126].

Across these varied studies, one relatively consistent finding is that although indications of
earlier differences are present, between-group differences are more easily identified at later
ages (see online supplemental materials for references). This pattern of results is consistent with
the notion reviewed above that development is iterative, with an infant’s own actions and
experiences guiding and constraining future learning [78]. Such a model predicts that even
small disruptions of early social adaptive action can yield progressively greater between-group
differences over time, culminating later in the marked symptomatology of ASD. Importantly,
recognition of development as an iterative process means that differences observed at later
times must be underway already at earlier ones.

Early Patterns of Preferential Orientation in Autism Spectrum Disorder and Transitions

Therein
Given the foundational nature of social skills disruption in ASD, as well as the profound
transitions in typical social development happening in early infancy, changes in preferential
orientation, engagement, and adaptation during the first weeks and months after birth are a
critical area of future ASD inquiry.

Existing data in infants later diagnosed with ASD suggest that one such mechanism, prefer-
ential orientation to the eyes, is not immediately diminished [32]. Levels of early eye-looking are
relatively high in infants with ASD. To be clear, the presence of these relatively high levels does
not necessarily indicate ‘normative’ or ‘intact’ function [32]; to the contrary, while the magnitude
of eye-looking at 2 months is relatively high, the underlying developmental processes are clearly
already different: rate-of-change in eye-looking, from at least 2 months onwards, differs
significantly between outcome groups. Moreover, infants later diagnosed with ASD exhibit
a slight but statistically significant increase in eye-looking at 2 months, which then declines
(Figure 3D); by contrast, typically developing infants exhibit a relative low point in eye-looking at
2 months, which then increases.

464 Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5

As reviewed above, the timing of these differences may relate directly to important transitions in Outstanding Questions
adaptive behavior: preferential orientation to faces (present at birth [43]) typically declines How do neonatal reflexive actions and
between 4 and 6 weeks [44] before beginning to increase at approximately 2 months [81]. predispositions transition into mutually
adapted social interaction in the first
Similar transitions during this same period are observed in orienting to auditory sounds [127] months of typical development? What
and imitating others [128]. At a neural level, these changes are thought to be accompanied by a changes at the level of brain networks
shift from subcortical to cortical control, with initial reflex-like predispositions (subserved by and gene expression accompany such
transitions?
subcortical structures) declining as cortical control matures [81].
How do infants’ early behaviors facili-
Taken as a whole, a very specific hypothesis emerges (Figure 3D): reflex-like orienting to the tate later attainment of normative
eyes of others may be initially, at least superficially, present in newborns with ASD, while the social developmental milestones?
latter phase of preferential eye-looking is disrupted. More broadly, in a wide range of other
sensory and behavioral domains, preferential orientation may initially be present in these infants, How do earlier-developing systems (e.
g., touch), as well as disruptions in
whilst early pivotal transitions (transitions that depend upon the way in which initial preferential
such systems (e.g., potential disrup-
orientation is integrated into mutually adaptive interaction) are disrupted. Critically, this hypoth- tions in affective touch in infants with
esis focuses scientific attention on key developmental transitions very early in life, and specifi- ASD), have the potential to constrain
cally on the progression from a reflexive/‘experience expectant’ phase of development (largely and canalize the development of later-
emerging systems?
subcortically mediated), to an interactive/‘experience dependent’ phase (with greater depen-
dence on cortical control) [96,97].
For children with delays in specific
milestones, is there a corresponding
To be clear, there is little evidence to suggest an outright failure of cortical control of voluntary delay in offset of related reflexes? Or,
preferential visual attention in ASD; to the contrary, data at later age points suggest a co-opting alternatively, do reflexes decline on
their own timeline, irrespective of other
of those cortical mechanisms by attention to other features of the environment, such as subsequent delays?
nonsocial, physical cues [107,129]. These data suggest future lines of inquiry, focused in
these first few months, on how early predispositions transition into mutually adapted social Is the transition from ‘experience
interaction. This line of inquiry should benefit from a direct link to decades of work from pertinent expectant’ reflexive action to ‘experi-
model systems [130], work that can now be brought to bear in guiding gene–brain–behavior ence dependent’ social interaction
accompanied by a shift from subcorti-
hypotheses of the pathogenesis of autism. Likewise, the role of other sensory systems in these cal to cortical control?
processes remains understudied; given the early development of the auditory and tactile
systems (affective touch in particular [53]), their role in constraining and influencing early Are typical predispositions for conspe-
development is a key area for future study. cific orienting present in newborns with
ASD?

Concluding Remarks
How and when do mechanisms of
Collectively, the data reviewed above, from both behavior and brain development in typical preferential orientation, signaling, and
infancy, showcase a system that is remarkably attuned to the social world, is mutually adapted infant–caregiver adaptation become
to caregiver behavior, and becomes progressively more so over time. From the first moments of disrupted in infants with ASD?
life, neonates exhibit a wide range of socially adaptive preferences and reflex-like responses
that serve to orient their attention towards caregivers as well as behaviors that serve as
important signals to those caregivers. These behaviors are adaptive because they occur within
an environment that depends upon a caregiver, one whose own actions are adapted to
optimally respond to the neonate’s and to further elicit such actions. This mutually adapted,
mutually reinforcing context of the infant–caregiver dyad is both the platform and the catalyst for
subsequent development: initially spontaneous reflex-like responses transition into remarkably
sensitive and contingent social action, all within the first months of life.

These findings, together with evidence from early normative transitions, provide an important
framework for future research in ASD by constraining hypotheses about what specific devel-
opmental transitions may be disrupted in ASD and when. For instance, rather than suggesting a
complete absence of preferential orientation to others from birth (as was hypothesized dating
back to Kanner [131]), these data identify a specific transitional period of early infancy, around
the second month of life, as a critical focus for future investigation, both for systems level

Trends in Cognitive Sciences, May 2018, Vol. 22, No. 5 465

neuroscience research (in both human and model systems) and for genetics research (guiding
and providing the quantitative traits for developmental gene expression and methylation
studies). These data further suggest that future analysis of potential disruptions in autism
might productively focus on mechanisms of preferential orientation, signaling, and, critically,
mutual adaptation between infant and caregiver, particularly during this transitional period
(see Outstanding Questions). The pursuit of these constrained hypotheses holds great promise
for yielding insight into the specific developmental processes that are disrupted in ASD and for
discovering new opportunities for innovative early interventions.

Acknowledgments
This work was supported by grants from the National Institute of Mental Health: NIMH R21 MH105816; NIMH P50
MH100029; NIMH 2P50 MH100029-6; and NIMH K01 MH108741. Additional support provided by the Marcus Founda-
tion, the Whitehead Foundation, the Simons Foundation, and the Georgia Research Alliance. We would also like to thank
Torrey Cohenour, Aiden Ford, Drew Kreuzman, Sarah Markert, Megan Micheletti, and Jack Olmstead, for helpful
comments on the manuscript, as well as Emily Ryu for assistance in gathering infant developmental milestone data.

Resources
i
www.brainspan.org

Appendix A Supplementary data

Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.tics.2018.
02.012.

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