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Caregiving influences on emotional learning and

regulation: applying a sensitive period model
Dylan G Gee

Early caregiving experiences play a central role in shaping A rich cross-species literature has begun to identify
corticolimbic development and emotional learning and the effects of caregiving experiences on corticolimbic
regulation. Given dynamic changes in corticolimbic maturation, circuitry and emotional behavior. Given marked changes
the effects of caregiving experiences are likely to depend on the in species-expected inputs and neuroplasticity across
developmental timing of exposure. Cross-species evidence development, caregiving experiences are likely to differ-
has identified timing-related differences in the effects of entially shape behavior during infancy, childhood, and
caregiving adversity. However, the extent to which adolescence [2–4]. However, much remains unknown
developmental differences in associations between caregiving about precise experience-related mechanisms and
adversity and corticolimbic circuitry align with a sensitive whether developmental differences in the effects of
period model has remained unclear. Converging evidence from caregiving experiences reflect sensitive periods [5].
studies of caregiver deprivation points to a sensitive period for Identifying specific timing-related effects of caregiving
caregiving influences on corticolimbic circuitry and emotional experiences and differentiating between experience-
development during infancy. By contrast, differential expectant and experience-dependent mechanisms is
associations between maltreatment and corticolimbic circuitry key to advancing conceptual models of caregiving envir-
at specific ages in childhood and adolescence may reflect onments and corticolimbic development.
experience-dependent mechanisms of plasticity. Delineating
sensitive periods of development and the precise experience- Sensitive periods of development
related mechanisms by which caregiving experiences influence During a sensitive period of heightened neuroplasticity, a
corticolimbic development is essential for refining conceptual
specific environmental input has a particularly strong
models and understanding risk and resilience following early
influence on a specific brain circuit, and plasticity is
adversity.
limited following this window [6,7]. Importantly, sensi-
tive periods are characterized by experience-expectant
Address
learning and are thought to reflect neural preparation to
Yale University, Department of Psychology, 2 Hillhouse Avenue,
encode species-expected environmental stimuli [8].
New Haven, CT 06511, United States
Recent years have witnessed transformative discoveries
of the molecular triggers (e.g., excitatory-inhibitory bal-
Corresponding author: Gee, Dylan G ([email protected])
ance) and brakes (e.g., perineuronal nets, myelin) that
control the onset and closure of sensitive periods, as
Current Opinion in Behavioral Sciences 2020, 36:177–184 well as the insight that sensitive period processes are
themselves malleable [7]. Unlike experience-expectant
This review comes from a themed issue on Sensitive and critical
periods
plasticity, which tends to occur early in development,
experience-dependent plasticity occurs in response
Edited by Catherine A Hartley and Willem E Frankenhuis
to individual experiences (which are not necessarily
For a complete overview see the Issue and the Editorial species-expected) and facilitates learning throughout
Available online 3rd December 2020 development [8]. The current review aims to apply a
https://doi.org/10.1016/j.cobeha.2020.11.003 critical lens to existing research on caregiving effects on
2352-1546/ã 2020 Elsevier Ltd. All rights reserved.
corticolimbic development to begin to delineate which
developmental differences in caregiving influences may
align with a sensitive period model and experience-
expectant versus experience-dependent plasticity.

Caregiving and corticolimbic development

Early experiences have profound and lasting effects on Decades of research have demonstrated the robust links
the developing brain and emotional behavior. Caregiving between caregiving and offspring emotional behavior [9],
is one of the strongest species-expected inputs for altricial with a growing literature focused on neurobiological
species early in life, and stable caregiving is critical to mechanisms. Cross-species evidence has demonstrated
emotional well-being [1]. From normative variation in that early caregiving experiences have particularly
caregiving behaviors to severe caregiving adversity, the strong effects on corticolimbic circuity involved in learn-
early environment actively shapes learning and behav- ing about salient aspects of the environment and
ioral repertoires in the affective domain for years to come. regulating emotion. Connections between regions such

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178 Sensitive and critical periods

as the medial prefrontal cortex (mPFC), amygdala, and naturalistic human studies of unfortunate events (e.g.,
hippocampus, which play a key role in regulating emotion institutionalized care) provide strong evidence for the
and guiding biologically relevant learning [10], may be importance of the timing of adversity. With its unique
especially impacted by adversity due to their dense study design, the Bucharest Early Intervention Project
innervation with glucocorticoid receptors and the devel- has highlighted a potential sensitive period related to
opmental timing of circuit maturation [11]. Whereas socioemotional development during the first two years
prefrontal regions and their connections with limbic of life. That is, youth who were exposed to caregiver
structures undergo protracted development, the amyg- deprivation via institutionalized care show more secure
dala matures relatively earlier and may be particularly attachment, more normative stress responses, and more
sensitive to the early social environment [12]. Though normative neurodevelopmental trajectories following
these connections undergo marked changes across devel- placement into a foster care intervention prior to
opment [13,14], functional connectivity at rest is already 24 months of age, relative to peers who were placed later
evident between the amygdala and regions such as ven- [31]. These findings highlight infancy as a particularly
tromedial prefrontal cortex (vmPFC) in infancy [15]. important time for caregiving influences, as well as the
Moreover, amygdala-mPFC functional connectivity at potential for the identification of sensitive periods to
rest among newborns is associated with negative affect inform interventions.
at six months of age [16] and with behavioral inhibition
at two years of age [17]. Environmental influences on Consistent evidence has shown that the absence of stable,
corticolimbic circuitry in early life may play an active role nurturing caregiving in the postnatal and infancy period
in shaping longer-term neural and behavioral phenotypes. disrupts corticolimbic development. Across species, early
For example, neural co-activations induced via experi- caregiver deprivation is associated with altered connec-
ences with caregivers may ‘entrain’ the system during a tivity between the amygdala and mPFC in mice [32], rats
highly plastic time in ways that shape intrinsic cortico- [33], non-human primates [23], and humans [24]. It is
limbic architecture and affective behaviors [18–20]. possible that these findings reflect a sensitive period
Moreover, the early sensitivity of the amygdala to envi- driven by experience-expectant mechanisms. Consistent
ronmental inputs may directly guide mPFC function with criteria for a sensitive period [7,34], infancy is a time
and connectivity [20] and influence later-developing of rapid and marked change in corticolimbic circuitry [35],
aspects of broader cortico-subcortical circuitry through and it is biologically plausible that this period is charac-
developmental cascades [21]. terized by heightened neuroplasticity. There is also some
specificity to the nature of the experience, the neural
Much of the research linking caregiving with emotional circuit affected, and the timing of the window during
development comes from studies of severe caregiving which caregiver deprivation has particularly strong effects
adversity. Alterations of the HPA axis [22] and cortico- [3]. However, evaluating sensitive period phenomena
limbic circuitry [23,24] appear to underlie effects of in human development is especially challenging, and
caregiving adversity on emotional learning [25] and regu- additional research will be necessary to more rigorously
lation [26] and likely contribute to increased risk for assess all relevant criteria [5,34]. In particular, it is rare
mental health disorders. However, increasingly evidence that longitudinal data are available to test whether effects
has also emerged linking normative variation in caregiv- of caregiver deprivation on corticolimbic circuitry persist
ing behavior with corticolimbic structure and function into adulthood.
[27]. For example, during childhood, caregiver sensitivity
is associated with amygdala volume and microstructure Although substantial evidence suggests that caregiving
of the amygdala and hippocampus [28], and negative adversity has the strongest effects when experienced
caregiving behavior is associated with amygdala activa- earlier in life [3,22,31], an alternative account suggests
tion and functional connectivity between the amygdala that risk may be highest when adversity occurs during
and superior parietal lobule [29]. In addition, caregiver specific windows that could occur later in childhood or
control experienced during childhood is associated with adolescence. Studies examining variation in the timing of
amygdala activation and structural integrity of the maltreatment have at times pointed to specific ages of
uncinate fasciculus during young adulthood [30]. These exposure during childhood or adolescence at which
studies further underscore the importance of caregiving in effects on corticolimbic structure or function in adulthood
healthy brain development. are pronounced [36–38,39]. These studies highlight
the complexity of interactions between developmental
Developmental differences in the effects of timing with the type of adversity exposure, sex, and
caregiving on corticolimbic circuitry regional specificity in the brain. For example, exposure
Non-human animal work that allows for manipulating the to maltreatment between ages 10 and 11 is specifically
timing of exposure shows that the effects of stress differ as related to amygdala volume in adulthood, relative to
a function of developmental timing [3]. Manipulating exposure at other ages during development [37], whereas
stress exposure is challenging in humans; however, sexual abuse at ages 3–5 and 11–13 is uniquely associated

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 Caregiving influences on emotional development Gee 179

with hippocampal volume in adulthood [36]. Among men, precocious maturation may signal a shift or premature
hippocampal volume in adulthood is associated with termination of a sensitive period of caregiving influences,
neglect, but not abuse, prior to age 7. By contrast, hippo- which could be associated with reduced plasticity. Future
campal volume in women is associated with abuse, but research will be important for understanding longer-term
not neglect, at ages 10–11 and 15–16 years [38]. However, effects, testing whether neural findings are specific to
it is not clear whether these developmental differences corticolimbic circuitry, and for further examining how
align with a sensitive period process, and experience- developmental patterns of acceleration converge or
dependent mechanisms may better explain such age- diverge across different domains such as puberty, cellular
related effects. As one example, maltreatment is unlikely aging, and neurodevelopment.
to be a plausible type of species-expected stimuli at a
specific developmental time [5]. Moreover, while these Early caregiving influences on emotional
findings in adulthood may suggest non-linear peaks in risk learning and regulation
throughout development, future studies during childhood Caregivers modulate offspring behavior in a number of
and adolescence will be important for understanding domains related to affective behavior, including influenc-
more proximal corticolimbic changes that may unfold ing what offspring learn and how they perceive the world
across development. around them. Encoding stable, reliable caregiver cues
that are associated with safety during an early sensitive
Yet another way in which caregiving adversity may alter period (e.g., infancy) may be essential to the roles that
corticolimbic development is by altering sensitive period caregivers play in modulating emotional learning and
processes themselves. In rodents, hippocampal and amyg- regulation later in development. Young offspring show
dala development, as well as some forms of emotional a preference for cues related to their caregiver, even when
learning, are accelerated following early adversity those cues are inherently aversive. For example, rodent
[40–42]. In humans, evidence suggests that the timing pups show approach behaviors toward an odor paired with
of structural and functional corticolimbic development a shock during a period when maternal presence main-
may also be accelerated following adversity [24,43,44]. As tains low levels of corticosterone and blocks amygdala
one example, while viewing fearful faces, children who plasticity [50]. Paralleling these findings in rodents,
experienced caregiver deprivation exhibit more mature recent evidence demonstrates similar caregiver-related
patterns of functional connectivity between the vmPFC learning in humans. Specifically, young children were
and amygdala (i.e., negative task-based connectivity), more likely to approach conditioned stimuli that were
which resemble those of adolescents and adults [24]. acquired in their caregiver’s presence and to avoid stimuli
Across species these effects have been mediated by acquired in the caregiver’s absence [51]. This attraction
corticosterone levels (cortisol in humans) [24], suggesting to caregiver-related cues and absence of avoidance learn-
that early caregiving adversity may prematurely stimulate ing is thought to facilitate attachment early in life and
the HPA axis in a way that contributes to precocious ensure that the offspring stays close to their caregiver [52].
corticolimbic and emotional development. Critically, these effects depend on developmental stage.
During a window from postnatal day (P)10 to P15, rodent
Such accelerated development may represent an ontoge- pup behavior depends on maternal presence, such
netic adaptation in the context of an early harsh environ- that pups continue to show approach behaviors if the
ment [45,46]. Consistent with this idea, children exposed mother is present. However, corticosterone and amygdala
to caregiver deprivation who show the more mature activation increase if the mother is absent, instantiating
phenotype of vmPFC-amygdala connectivity also display threat learning and avoidance behaviors [50], potentially
lower separation anxiety [24]. These findings are in line to facilitate survival when offspring engage in exploration
with evidence that stronger inverse amygdala-mPFC independently.
functional connectivity is associated with lower internal-
izing symptoms among youth exposed to early family Consistent with the effects of caregiver presence on
adversity [47] and that greater prefrontal control (specifi- corticosterone levels and amygdala plasticity in rodents,
cally, superior frontal gyrus and dorsal anterior cingulate caregivers buffer stress physiology and HPA axis reactiv-
cortex) of amygdala reactivity during emotion regulation ity in infant macaques [53] and in humans [54]. Suggest-
is associated with lower depressive symptoms following ing a potentially related mechanism by which caregivers
child maltreatment [48]. Moreover, recent work shows modulate affective behavior early in life, during child-
that the more mature pattern of vmPFC-amygdala hood, caregivers suppress amygdala reactivity and phasi-
connectivity is also associated with slower telomere short- cally induce a pattern of amygdala-mPFC functional
ening and pubertal tempo [49], which may further connectivity that may be more strongly regulatory [55].
suggest protective effects in the context of evidence Paralleling this modulation of amygdala-mPFC circuitry,
demonstrating accelerated cellular aging following early children also show enhanced regulatory behavior in
life adversity. However, there are likely to be long-term an affective context in the presence of their mother
consequences of accelerated development. Such compared with a stranger. The effects of caregivers on

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180 Sensitive and critical periods

cortisol reactivity [54] as well as on regulatory behavior environment and in regulating their behavior, particularly
and amygdala-mPFC circuitry [55] are specific to child- early in life. However, instead of caregiver effects on
hood, and not adolescence. These findings suggest that emotional learning and regulation during childhood
caregivers may serve an external regulatory function reflecting a sensitive period itself, it may be that encoding
while corticolimbic circuitry is still developing. With time reliable cues related to the support of caregivers earlier in
and as this circuitry matures, reliance on external regula- life allows for those cues to exert these unique effects
tion may decrease as regulatory abilities become inter- during childhood.
nalized to facilitate independent emotion regulation, and
other major attachment figures such as close peers or Consistent with this idea, increasing cross-species evi-
romantic partners may take on an increasing role in social dence suggests that early caregiving adversity disrupts the
buffering [46,56] (Figure 1). In humans, caregiver pres- ways in which caregivers guide learning and buffer
ence has also been shown to increase discrimination emotional reactivity in later stages of development. In
between threat and safety cues during childhood, but rodents, infant maltreatment is associated with reduced
not adolescence [57]. In these ways, caregivers play a effects of maternal presence on threat learning during
central role in shaping what children learn about their infancy [58,59]. Interestingly, maltreatment during

Figure 1

Caregiver Close Romantic

Buffering Peers Partners
Sensitive
Period for
Caregiving
Relationship

Prefrontal
Cortex

Corticolimbic Circuitry and Function

Amygdala

Reliance on Intrinsic Emotion Regulation

Reliance on extrinsic Emotion Regulation

Infancy Childhood Adolescence Adulthood

Current Opinion in Behavioral Sciences

Caregiver influences on corticolimbic circuitry related to emotion regulation across development.

Cross-species evidence suggests a sensitive period during infancy through which caregiving has particularly strong influences on corticolimbic
development (including mPFC-amygdala connectivity) and longer-term emotional behavior. Caregivers regulate amygdala function during infancy
(demonstrated in rodents, hypothesized in humans) and childhood (demonstrated in humans), and not in adolescence. The shift away from
reliance on caregivers for extrinsic regulation may be accompanied by increased capacity for intrinsic emotion regulation around the transition to
adolescence. Social buffering continues across the lifespan, with different primary attachment figures potentially serving a regulatory function at
distinct developmental stages. Because of heightened plasticity to caregiving influences early in life, severe disruptions in caregiving during
infancy may interfere with learning reliable, safe caregiver cues in a way that interferes with normative caregiver shaping of emotional learning and
regulation later in development. Adapted with permission from Ref. Gee [46].

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 Caregiving influences on emotional development Gee 181

infancy has differential effects on maternal buffering isolation. An important area for future research will be
during infancy versus adolescence. Whereas maltreat- examining how timing-related factors (e.g., age of expo-
ment completely disrupts maternal buffering at PN18, sure, chronicity, duration) interact with key experiential
maternal buffering is present but weaker at PN28 [59]. In dimensions of adversity, such as the extent to which
non-human primates, infant maltreatment is associated adversity is characterized by threat versus deprivation
with weaker maternal buffering of stress-induced cortisol [64], predictability [65], controllability, and/or caregiver
increases [60]. In humans, caregiver deprivation early in involvement [for review, see Ref. 66]. As one example,
life interferes with caregiver buffering of amygdala reac- independent of severity, adversity perpetrated by a care-
tivity during childhood [61]. However, effects are het- giver or adversity that involves dyadic caregiver/child
erogeneous, such that approximately 40% of youth who exposure may have stronger or differential effects on
experienced caregiver deprivation exhibit caregiver buff- corticolimbic development than adversity that does not
ering, and those youth also experience steeper declines in involve a caregiver [67]. Further delineating how specific
separation anxiety over a period of three years. Thus, the features of adversity differentially impact outcomes, and
ability to experience caregiver buffering of amygdala how those effects differ by developmental stage, could
reactivity may enhance resilience within this group at inform efforts to optimize risk identification based on
elevated risk for anxiety. Taken together, these findings developmental stage or the nature of adversity exposure.
suggest that while caregiver buffering itself may not be
consistent with a sensitive period phenomenon, caregiv- Conclusions
ing adversity during a sensitive period in infancy may Cross-species findings demonstrate that early caregiving
disrupt the encoding of stable, safe caregiver cues that experiences play a central role in shaping the develop-
are likely to be important for caregiver influences on ment of learning and regulation in the affective domain.
emotional learning and regulation later in development. Adverse caregiving can alter corticolimbic development
and normative processes such as caregiver buffering
Future directions of amygdala reactivity, with lasting implications for
Despite a growing literature on developmental differ- emotional behavior and mental health. While increasing
ences in the effects of caregiving on corticolimbic devel- evidence demonstrates that caregiving influences depend
opment, the experience-related mechanisms underlying on the timing of experiences, it is unclear under what
these influences remain largely unknown. Ongoing circumstances earlier adversity is more consequential or
research that evaluates which developmental differences whether there are windows of development throughout
are consistent with the criteria for a sensitive period childhood and adolescence when caregiving adversity has
will be essential to advancing conceptual models and the strongest effects. Moreover, much remains unknown
understanding the mechanisms by which early caregiving about the experience-related mechanisms of plasticity
experiences become biologically embedded to shape that link early caregiving inputs with affective outcomes.
emotional development. It is rare that distinct models Caregiver deprivation experienced during infancy has
of experience-related mechanisms have been directly persistent effects on corticolimbic development and later
compared, and rigorously testing a sensitive period model caregiver buffering, which may reflect an early sensitive
in humans presents various challenges [5,62], including period for attachment and learning stable caregiver cues.
the complex and multifaceted nature of caregiving Future research will be essential for testing whether
experiences, the protracted time needed to assess effects developmental differences in caregiving influences may
on mature function, and the inability to test for molecular reflect experience-expectant or experience-dependent
regulators and direct markers of plasticity in humans. mechanisms, or influences on sensitive period timing
In addition, it is important to acknowledge that experi- itself. Refining conceptual models based on such knowl-
ence-expectant and experience-dependent learning are edge has important implications for promoting resilience
unlikely to be completely independent processes [8], and following early adversity and could be leveraged to
experience-related learning is unlikely to reflect a single enhance risk identification or tailor interventions based
process or model. In this regard, cross-species research on factors such as developmental stage.
will continue to be essential to testing hypotheses about
sensitive periods [63], and bridging between formal Conflict of interest statement
modeling and empirical studies may offer powerful Nothing declared.
insights [62]. Further, study designs will need to
incorporate precise measurement of timing of exposures
and extend longitudinal follow-up to enhance the Acknowledgements
This work was supported by the National Institutes of Health (NIH)
ability to test sensitive period models in human Director’s Early Independence Award (DP5OD021370), Brain & Behavior
neurodevelopment. Research Foundation (National Alliance for Research on Schizophrenia and
Depression; NARSAD) Young Investigator Award, Jacobs Foundation Early
Career Research Fellowship, and the Society for Clinical Child and
Lastly, research on developmental differences in caregiv- Adolescent Psychology (Division 53 of the American Psychological
ing effects has largely focused on timing-related factors in Association) Richard ‘Dick’ Abidin Early Career Award and Grant.

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182 Sensitive and critical periods

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