Original Investigation | Pediatrics

Level of Attention to Motherese Speech as an Early Marker

of Autism Spectrum Disorder
Karen Pierce, PhD; Teresa H. Wen, PhD; Javad Zahiri, PhD; Charlene Andreason, MA; Eric Courchesne, PhD; Cynthia C. Barnes, PhD;
Linda Lopez, BA; Steven J. Arias, PhD; Ahtziry Esquivel, BS; Amanda Cheng, BS

Abstract Key Points

Question Can levels of attention
IMPORTANCE Caregivers have long captured the attention of their infants by speaking in
toward motherese speech, indexed
motherese, a playful speech style characterized by heightened affect. Reduced attention to
through eye tracking, be used as a
motherese in toddlers with autism spectrum disorder (ASD) may be a contributor to downstream
diagnostic marker of autism spectrum
language and social challenges and could be diagnostically revealing.
disorder (ASD), and are they associated
with social and language abilities?
OBJECTIVE To investigate whether attention toward motherese speech can be used as a diagnostic
classifier of ASD and is associated with language and social ability. Findings In this diagnostic study of 653
toddlers aged 12 to 48 months, levels
DESIGN, SETTING, AND PARTICIPANTS This diagnostic study included toddlers aged 12 to 48 of fixation on motherese speech were
months, spanning ASD and non-ASD diagnostic groups, at a research center. Data were collected high in toddlers without ASD but
from February 2018 to April 2021 and analyzed from April 2021 to March 2022. significantly reduced in toddlers with
ASD. If a toddler fixated on motherese
EXPOSURES Gaze-contingent eye-tracking test. speech at or below 30%, the probability
of that toddler being accurately
MAIN OUTCOMES AND MEASURES Using gaze-contingent eye tracking wherein the location of a identified as ASD was 94% and also
toddler’s fixation triggered a specific movie file, toddlers participated in 1 or more 1-minute signified an association with reduced
eye-tracking tests designed to quantify attention to motherese speech, including motherese vs social and language abilities.
traffic (ie, noisy vehicles on a highway) and motherese vs techno (ie, abstract shapes with music).
Meaning The findings suggest that
Toddlers were also diagnostically and psychometrically evaluated by psychologists. Levels of fixation
levels of attention to motherese speech
within motherese and nonmotherese movies and mean number of saccades per second were
may be a diagnostic and prognostic
calculated. Receiver operating characteristic (ROC) curves were used to evaluate optimal fixation
marker of ASD.
cutoff values and associated sensitivity, specificity, positive predictive value (PPV), and negative
predictive value. Within the ASD group, toddlers were stratified based on low, middle, or high levels
of interest in motherese speech, and associations with social and language abilities were examined. + Supplemental content
Author affiliations and article information are
RESULTS A total of 653 toddlers were included (mean [SD] age, 26.45 [8.37] months; 480 males listed at the end of this article.

[73.51%]). Unlike toddlers without ASD, who almost uniformly attended to motherese speech with a
median level of 82.25% and 80.75% across the 2 tests, among toddlers with ASD, there was a wide
range, spanning 0% to 100%. Both the traffic and techno paradigms were effective diagnostic
classifiers, with large between-group effect sizes (eg, ASD vs typical development: Cohen d, 1.0 in the
techno paradigm). Across both paradigms, a cutoff value of 30% or less fixation on motherese
resulted in an area under the ROC curve (AUC) of 0.733 (95% CI, 0.693-0.773) and 0.761 (95% CI,
0.717-0.804), respectively; specificity of 98% (95% CI, 95%-99%) and 96% (95% CI, 92%-98%),
respectively; and PPV of 94% (95% CI, 86%-98%). Reflective of heterogeneity and expected
subtypes in ASD, sensitivity was lower at 18% (95% CI, 14%-22%) and 29% (95% CI, 24%-34%),
respectively. Combining metrics increased the AUC to 0.841 (95% CI, 0.805-0.877). Toddlers with
ASD who showed the lowest levels of attention to motherese speech had weaker social and language
abilities.

(continued)

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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Abstract (continued)

CONCLUSIONS AND RELEVANCE In this diagnostic study, a subset of toddlers showed low levels of
attention toward motherese speech. When a cutoff level of 30% or less fixation on motherese
speech was used, toddlers in this range were diagnostically classified as having ASD with high
accuracy. Insight into which toddlers show unusually low levels of attention to motherese may be
beneficial not only for early ASD diagnosis and prognosis but also as a possible therapeutic target.

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Introduction
Caregivers have long captured the attention of their infants and toddlers by speaking in motherese,
a playful speech style characterized by exaggerated intonation contours, simple grammar, high pitch,
and slow tempo, also known as parentese or infant-directed speech.1 Infants prefer to listen to this
speech style relative to adult-directed speech from the first days of life,2 a preference ubiquitous
across cultural and geographical boundaries,3 suggesting a possible genetic basis.4 Studies have
noted that this highly affective speech style stimulates joint attention and learning and is associated
with improved language acquisition, affective engagement, and emotional reactivity.1,5,6
It has long been known that children with autism spectrum disorder (ASD) show unusual and
sometimes absent responses to auditory information in their environment. For example, children
may fail to respond when their name is called7,8 or exhibit a poor understanding of word
meanings.9,10 At the neural level, studies commonly report significantly reduced functional brain
activity10-13 or delayed timing in response to speech sounds.14-16 Using behavioral techniques such as
turning the head toward sounds emitted from a tape recorder, Kuhl and colleagues17 showed that
70% of children with ASD preferred to listen to computer-generated sounds over motherese, a
finding that has been replicated.18,19 Yet, reduced response to motherese speech is not commonly
reported among children with non-ASD delays, suggesting possible specificity for ASD and utility as a
diagnostic marker.20
In studies of typically and atypically developing children, associations between exposure to
motherese speech and early word recognition,5 mean length of utterance,21 and receptive language
ability22 have been reported. Given the experience-dependent mechanisms that support learning
during the first years of life,23-26 infants who do not pay attention to motherese speech—or human
speech in general—would likely have more impaired language ability than children who pay close
attention to social speech. In a brain imaging study, toddlers with ASD who showed the lowest levels
of attention to motherese speech also showed the lowest levels of neural functional activation in
speech-processing regions and lower language abilities than toddlers who paid greater attention to
motherese speech.27
Eye tracking is a relatively new approach for rapidly and accurately characterizing attention in
ASD28-37 and holds promise as a screening and diagnostic tool.31,33 Eye-tracking studies, however,
have been largely restricted to the visual domain and have demonstrated reduced attention to social
visual images in ASD.30,38-44 Although there are some exceptions,45 few studies have leveraged
eye-tracking technology to understand attention patterns within the auditory domain, particularly in
response to speech sounds. In theory, this could be achieved through gaze-contingent technology
wherein the location where a toddler looks on a monitor triggers specific speech and
nonspeech sounds.
While visual attention is commonly indexed as a percent fixation metric (eg, percent fixation
time on faces), other eye-tracking metrics, such as saccades, may also provide useful information.
Unique saccade profiles can be associated with levels of anxiety46,47 but are not necessarily
correlated with overall fixation quantities. For example, studies have shown dissociations between
saccade and fixation levels in ASD, with some toddlers with ASD who exhibit high levels of fixation on
nonsocial images also showing low saccade rates.31,32 Examining saccade metrics in conjunction with

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

traditional percent fixation metrics could provide new insight regarding how toddlers with ASD
visually and auditorily examine their world. This may be essential for improving the diagnostic
classification accuracy of eye-tracking tests and help to uncover unique biological subtypes of ASD.
The aim of this study was to investigate whether level of attention toward motherese speech can be
used as a diagnostic classifier of ASD and is associated with language and social ability.

Methods
This diagnostic study was approved by the institutional review board at the University of California
San Diego (UCSD). Parents gave written informed consent, and all testing occurred at the UCSD
Autism Center. The study followed the Standards for Reporting of Diagnostic Accuracy (STARD)
reporting guideline (eMethods in Supplement 1). Race and ethnicity information was obtained via
parent report and was included as required for federal grants; toddlers’ race and ethnicity were
categorized per National Institutes of Health definitions. Categories for race were African
American/Black, American Indian/Alaska Native, Asian, Native Hawaiian/Pacific Islander, White,
more than 1 race, and not reported, unknown, or other. Ethnicity was categorized as Hispanic or
Latino, not Hispanic or Latino, and unknown or not reported.

Participants and Clinical Testing

Toddlers were recruited through 2 mechanisms: community referrals (eg, website) or a general
population-based screening method called Get SET Early,48 using the Communication and Symbolic
Behavior Scales Developmental Profile Infant-Toddler Checklist,49,50 that results in the detection of
ASD as young as 12 months.48,51 Toddlers younger than 30 months who were referred were invited
for a reevaluation every 9 to 12 months until their third birthday, when a final diagnosis was given.
Toddlers aged 12 to 48 months participated in 1 or more motherese eye-tracking tests:
motherese vs traffic (ie, noisy, moving vehicles on a highway), motherese vs techno (ie, moving
shapes with musical sounds), and motherese vs flat affect. Across all tests, 11% of the sample was
excluded for a range of reasons such as inattention to the video. Details regarding recruitment,
exclusion, and testing overlap are given in the eMethods and eFigures 1 to 3 in Supplement 1.
Toddlers and their parents participated in a series of tests including the Autism Diagnostic
Observation Schedule (ADOS),52 the Mullen Scales of Early Learning,53 and the Vineland Adaptive
Behavior Scales.54 All assessments were administered by ADOS-certified, licensed clinical
psychologists (C.C.B. and S.J.A.) blind to eye-tracking results.
Based on diagnoses given at the final diagnosis age, toddlers were categorized into 5 contrast
groups (ASD, ASD features, delay, typical development [TD], and typical sibling of an ASD proband).
Details regarding diagnostic criteria and clinical scores are given in the Table and eFigure 4 and the
eMethods in Supplement 1.

Apparatus and Procedure

Either a Tobii T120 (365 toddlers [55.90%]) or Tobii Pro Spectrum 600 Hz (288 toddlers [44.10%])
eye tracker in combination with E-Prime software, version 3.0 (Psychology Software Tools), was used
to create gaze-contingent paradigms wherein the x-y coordinate of a toddler’s fixation triggered the
appearance of a specific movie file. More details are given in the eMethods and eFigure 5 in
Supplement 1.

Dog-Cat Gaze-Contingent Preexperiment Training

Toddlers were introduced to the concept of gaze contingency prior to the experiment. Details are
given in the eMethods and eFigure 6 in Supplement 1.

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Motherese Paradigms
Toddlers were presented with a series of 3 paradigms designed to quantify interest in motherese
speech. Each of the paradigms consisted of 2 movies placed side by side, with 1 side always
containing an actress speaking in a motherese style, using speech that contained high rates of
questions, inflections, and emotional prosody.1,55 In the motherese vs traffic paradigm, the
contrasting movie depicted cars moving on a busy highway with accompanying car horns and traffic
noise, while in the motherese vs techno paradigm, the contrasting movie contained moving abstract
shapes and numbers and was accompanied by musical chords. In the motherese vs flat affect
paradigm, the same actress was shown in both movies, reading from identical scripts, but in the

Table. Clinical Characteristics of Toddlers Who Completed 1 or More Motherese Eye-Tracking Tests

Toddlers (N = 653)a
ASD ASD features Delay or other TD TypSibASD
Characteristic (n = 422) (n = 29) (n = 75) (n = 115) (n = 12)
Sex
Female 100 (23.70) 9 (31.03) 26 (34.67) 34 (29.57) 4 (33.33)
Male 322 (76.30) 20 (68.97) 49 (65.33) 81 (70.43) 8 (66.67)
Age, mean (SD), mo
Motherese vs traffic 26.71 (7.38) 26.55 (9.54) 22.21 (8.67) 25.44 (8.52) 22.33 (9.85)
Motherese vs techno 26.94 (7.81) 27.04 (9.08) 24.07 (9.93) 25.35 (8.51) 23.33 (11.45)
Motherese vs flat 28.01 (8.66) 29.26 (8.81) 24.13 (10.04) 28.21 (8.15) 23.13 (9.69)
affect
Ethnicity
Hispanic or Latino 169 (40.05) 10 (34.48) 30 (40.00) 15 (13.04) 1 (8.33)
Not Hispanic or Latino 219 (51.89) 17 (58.62) 37 (49.33) 86 (74.78) 10 (83.33)
Unknown or not 34 (8.06) 2 (6.90) 8 (10.67) 14 (12.17) 1 (8.33)
reported
Race
African 7 (1.66) 1 (3.45) 1 (1.33) 6 (5.22) 0
American/Black
American Indian/ 5 (1.18) 1 (3.45) 2 (2.67) 0 0
Alaska Native
Asian 69 (16.35) 0 5 (6.67) 8 (6.96) 0
Native Hawaiian/ 3 (0.71) 1 (3.45) 1 (1.33) 0 0
Pacific Islander
White 218 (51.66) 19 (65.52) 46 (61.33) 72 (62.61) 10 (83.33)
>1 Race 45 (10.66) 4 (13.79) 3 (4.00) 14 (12.17) 1 (8.33)
Not reported, 75 (17.77) 3 (10.34) 17 (22.67) 15 (13.04) 1 (8.33)
unknown, or otherb
Mullen T score,
mean (SD)53
Visual reception 34.73 (13.33) 50.62 (11.00) 45.19 (9.96) 55.23 (11.03) 52.33 (7.75)
Fine motor 34.91 (17.67) 43.93 (7.67) 44.75 (11.45) 51.90 (8.73) 50.00 (9.28)
Receptive language 29.10 (15.15) 44.86 (8.89) 40.55 (11.83) 51.33 (10.99) 54.83 (16.57)
Expressive language 28.00 (16.06) 46.28 (9.25) 34.20 (10.85) 51.17 (10.24) 57.58 (10.15)
Early learning 67.47 (21.04) 93.24 (11.05) 83.04 (14.34) 104.80 (14.61) 109.42 (13.23)
composite
Vineland, mean (SD)54
Communication 77.45 (16.67) 94.34 (9.44) 87.56 (12.96) 100.55 (9.26) 100.00 (7.21)
Daily living 82.24 (13.22) 92.97 (12.73) 92.11 (10.83) 96.77 (11.42) 99.08 (8.98)
Socialization 81.80 (13.64) 91.72 (14.52) 90.67 (12.00) 100.23 (9.69) 100.42 (7.43)
Abbreviations: ADOS, Autism Diagnostic Observation
Motor skills 90.66 (11.45) 97.41 (13.75) 94.12 (11.66) 99.31 (9.62) 100.36 (4.59) Schedule; ASD, autism spectrum disorder; RRB,
Adaptive behavior 79.21 (11.60) 91.72 (11.13) 88.03 (11.23) 98.19 (10.38) 98.83 (8.22) restricted and repetitive behavior; SA/CoSo, social
composite affect and communication total score; TD, typical
ADOS score, development; TypSibASD, typical sibling of an
mean (SD)52
ASD proband.
SA/CoSo 13.70 (4.31) 5.21 (3.72) 3.24 (2.29) 2.67 (1.94) 2.83 (1.27) a
Data are presented as the number (percentage) of
RRB 5.68 (1.75) 2.90 (1.47) 1.72 (1.28) 1.37 (1.21) 0.75 (1.06)
toddlers unless otherwise indicated.
Total 19.39 (5.09) 8.10 (3.72) 4.96 (2.51) 4.04 (2.21) 3.58 (1.98) b
Other was not broken down further.

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contrasting movie, she used a flat affect, reading the script in a monotone voice. The movies were
available for approximately 60 seconds, and toddlers used the direction of their gaze to control the
amount of time each movie was played. Areas of interest (AOIs) were drawn on either side and
consisted of each movie in its entirety (eg, motherese AOI or traffic AOI). To assess test-retest
reliability, eye-tracking tests were repeated in a subset of toddlers 1 to 12 or more months following
their initial eye-tracking session.

Statistical Analyses
Primary analyses were conducted using R, version 4.0.2 (R Project for Statistical Computing), and
SPSS, version 28 (IBM). Between-group differences were assessed using 1-way analyses of
covariance with sex and age as covariates. The Tukey honestly significant difference test was used to
perform post hoc, pairwise comparisons of group differences. Two-sided P < .05 indicated statistical
significance. Ninety-five percent CIs of the mean differences between groups were calculated, and
effect sizes are reported using η2 and Cohen d, as appropriate. Test-retest reliability was examined
using intraclass correlations (ICCs; model 2, 1).56 Data were collected from February 2018 to April
2021 and were analyzed from April 2021 to March 2022.

Total Looking Time, Attention Toward Motherese Speech, and Number of Saccades
To assess whether overall attention differed between diagnostic groups, total looking time collapsed
across AOIs was calculated for each paradigm. Time spent fixating within each AOI (eg, motherese
or traffic) was divided by total looking time to determine a percent fixation value for each participant
in each paradigm. The number of saccades per second was calculated for each participant as n – 1
fixations divided by the total looking time within motherese and nonmotherese AOIs.

Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value,

and ROC Curve Analyses
For diagnostic classification accuracy analyses, toddlers were designated as having ASD or not having
ASD (ie, ASD features, delay, typical sibling of an ASD proband, and TD) based on their most recent
diagnostic evaluation. A receiver operating characteristic (ROC) curve was generated for each test
and used to determine the optimal percent fixation and saccades per second associated with
specificity of 96% or greater. A high specificity rate was chosen given the expense and anxiety
associated with a false-positive result.57 To assess whether combining metrics enhanced
classification accuracy, reduced error pruning was applied as the classifier within Waikato
Environment for Knowledge Analysis (WEKA)58,59 using both percent fixation on motherese and
saccades per second (eMethods in Supplement 1).

Association Between Motherese Fixation Levels, Social and Language Ability, and Age
Pearson correlations were used to examine motherese fixation and social and language associations
(eMethods in Supplement 1). For interpretative simplicity, toddlers were also stratified into
subgroups of high, medium, and low levels of fixation toward motherese, defined as follows: fixation
of 30% or less, low motherese attention; fixation of 70% or more, high motherese attention; and
the remaining toddlers, middle motherese attention. Differences in clinical profiles between each
subgroup were examined.

Results
Of 736 toddlers who participated in 1 or more motherese eye-tracking tests, 653 (88.72%) were
included in the final analyses. The mean (SD) age was 26.45 (8.37) months; 173 (26.49%) were
female, and 480 (73.51%) were male. A total of 15 (2.30%) were African American/Black; 8 (1.23%),
American Indian/Alaska Native; 82 (12.56%), Asian; 5 (0.77%), Native Hawaiian/Pacific Islander; 365
(55.90%), White; and 67 (10.26%), more than 1 race; for 111 (17.00%), race was unknown, not

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reported, or other. A total of 225 (34.46%) were Hispanic or Latino and 369 (56.51%), not Hispanic
or Latino; for 59 (9.03%), ethnicity was unknown or not reported. Of the 653 toddlers, 422 (64.62%)
had ASD, 104 (15.93%) had non-ASD delays, and 127 (19.45%) had TD; 588 (90.05%) participated in
the motherese vs traffic paradigm, 479 (73.35%) in the motherese vs techno paradigm, and 389
(59.57%) in the motherese vs flat affect paradigm. Toddlers with ASD represented a wide range of
ability and disability in terms of adaptive behavior, cognitive and language ability, and autism
symptom severity. Details regarding clinical score distributions are given in the Table and eFigure 4 in
Supplement 1.

Total Looking Time

There were no to minimal between-group differences in total looking time, depending on the
paradigm. Details are given in the eResults in Supplement 1.

Attention Toward Motherese Speech as Indexed by Percent Fixation

Unlike toddlers without ASD, who almost uniformly attended to motherese speech with a median
level of 82.85% and 80.75% across the traffic and techno tests, respectively, among toddlers with
ASD, there was a wide range spanning from 0% to 100%. Differences in percent fixation levels were
significant across the traffic (F4,581 = 28.08; P < .001; η2 = 0.15) and techno (F4,472 = 26.67; P < .001;
η2 = 0.18) paradigms, with toddlers with ASD fixating on the motherese videos significantly less than
all other diagnostic groups (except motherese vs traffic among toddlers with ASD vs typical siblings
of an ASD proband). For example, in the techno paradigm, the mean (SD) motherese fixation value
for toddlers with TD was 76.36% (19.73%), whereas for toddlers with ASD, the mean was 50.08%
(27.56%) (ASD vs TD mean [SD] difference, 26.28% [2.78%]; P < .001; Cohen d, 1.0). However, some
toddlers with ASD had high levels of fixation on motherese at or near 100% values. Overall
associated effect sizes were large for ASD vs other diagnostic groups, ranging from 0.79 to 1.22
across both paradigms. In contrast, there were only small between-group differences in the flat
affect paradigm (F4,382 = 3.49; P = .008; η2 = 0.03) with associated small effect sizes (Figure 1 and
Figure 2). Age was a significant covariate for both the traffic and flat affect paradigms (traffic,
F1,581 = 22.66; P < .001; η2 = 0.03; flat affect, F1,382 = 11.27; P < .001; η2 = 0.03). Sex was a significant
covariate only for the motherese vs traffic paradigm (F1,581 = 9.01; P = .003; η2 = 0.01). Pairwise
comparisons of group differences and sex differences are given in the eResults, eTable 1, and
eFigure 7 in Supplement 1.

Number of Saccades
Similar to our eye-tracking tests of social visual attention,32,33 toddlers in the low motherese
attention group showed a significantly increased number of saccades when viewing the social
motherese AOIs (motherese vs techno paradigm: low motherese attention vs TD, 2.34 saccades vs
1.56 saccades; F6,470 = 3.17; P = .005; η2 = 0.04; motherese vs traffic paradigm: low motherese
attention vs TD, 2.39 saccades vs 1.68 saccades; F6,579 = 14.88; P < .001; η2 = 0.13). Conversely,
across diagnostic groups, saccade rates were largely comparable when attending to nonsocial AOIs
(Figure 3). Correlations across paradigms are given in the eResults and eFigure 8 in Supplement 1.

Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and ROC
Curve Analyses
Using a value of 30% fixation or less on motherese as the cutoff value resulted in sensitivity of 18%
(95% CI, 14%-22%), specificity of 98% (95% CI, 95%-99%), positive predictive value (PPV) of 94%
(95% CI, 86%-98%), and negative predictive value (NPV) of 40% (95% CI, 36%-45%) and an
associated area under the ROC curve (AUC) of 0.733 (95% CI, 0.693-0.773) for the traffic paradigm
and 29% (95% CI, 24%-34%) sensitivity, 96% (95% CI, 92%-98%) specificity, 94% (95% CI,
86%-98%) PPV, and 41% (95% CI, 36%-46%) NPV and an associated AUC of 0.761 (95% CI, 0.717-
0.804) for the techno paradigm. In contrast, values were low for the flat affect paradigm, which had

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

an AUC of 0.597 (95% CI, 0.541-650). Combining saccades per second with percent fixation metrics
across the traffic and techno paradigms increased the AUC to 0.841 (95% CI, 0.805-0.877).
Diagnostic accuracy cross-tabulation tables and 95% CIs are provided in eTables 2 and 3 in
Supplement 1. Given the lack of diagnostic classification accuracy and small effect sizes, the flat affect
paradigm was not considered in further analyses.

Figure 1. Motherese Eye-Tracking Test Performance

A Motherese vs traffic B Motherese vs techno

4 FP (n = 213) 6 FP (n = 162)
100 0 100 0

80 20 80 20
Fixation motherese, %

Fixation motherese, %
Fixation traffic, %

Fixation techno, %
60 40 60 40

40 60 40 60

20 80 20 80
67 TP 91 TP
F4581 = 28.08, P <.001 F4472 = 26.67, P <.001
0 100 0 100

ASD ASD Delay TD TypSibASD ASD ASD Delay TD TypSibASD

(n = 375) features (n = 70) (n = 106) (n = 11) (n = 317) features (n = 53) (n = 73) (n = 10)
(n = 26) (n = 26)

C Motherese vs flat affect

3 FP (n = 162)
100 0

80 20
Fixation motherese, %

Fixation flat affect, %

60 40

40 60

20 80
10 TP

F4382 = 3.49, P =.008

0 100

ASD ASD Delay TD TypSibASD

(n = 227) features (n = 47) (n = 84) (n = 7)
(n = 24)

Box plots show the raw data for each of the motherese eye-tracking tests across 5 major example, within the motherese vs traffic paradigm, if a toddler fixated on motherese
diagnostic groups. Middle line indicates median value; upper and lower bounds of the 90% of the time, he or she had a corresponding value of 10% fixation in traffic. ASD
box, IQR; whiskers, range; dots, individual participants; and triangles, the mean. Because indicates autism spectrum disorder; FP, false positive; TD, typical development; TP, true
tests are all preferential looking paradigms, points along the y-axes sum to 100%; for positive; and TypSibASD, typical sibling of an ASD proband.

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Figure 2. Effect Size and Area Under Receiver Operating Characteristic (ROC) Curve (AUC)

A Motherese vs traffic B Motherese vs techno

1.0 1.0
ASD 0.88 0.82 0.84 0.8 ASD 1.01 0.79 1.00 1.22

0.8 0.8
ASD features 0.88 0.12 0.11 0.10 ASD features 1.01 0.27 0.06 0.27

0.6 0.6
Delay 0.82 0.12 0.01 0.02 Delay 0.79 0.27 0.24 0.56
0.4 0.4

TD 0.84 0.11 0.01 0.01 TD 1.00 0.06 0.24 0.36

0.2 0.2

TypSibASD 0.8 0.10 0.02 0.01 TypSibASD 1.22 0.27 0.56 0.36
0 0

ASD ASD Delay TD TypSibASD ASD ASD Delay TD TypSibASD

features features

C Motherese vs flat affect D AUCs

1.0
1.0
ASD 0.07 0.31 0.42 0.47

0.8 0.8
Percentage fixation motherese
ASD features 0.07 0.27 0.35 0.42
Techno paradigm (AUC: 0.761)
Traffic paradigm (AUC: 0.733)

Sensitivity
0.6 0.6
Delay Percentage saccades/s motherese
0.31 0.27 0.12 0.20
Techno paradigm (AUC: 0.704)
0.4 0.4 Traffic paradigm (AUC: 0.643)
TD 0.42 0.35 0.12 0.05 Percentage fixation motherese and
0.2 saccades/s motherese
0.2
Traffic and techno combined
TypSibASD 0.47 0.42 0.20 0.05 (AUC: 0.841)
0
0
ASD ASD Delay TD TypSibASD 0 0.2 0.4 0.6 0.8 1.0
features 1 – Specificity

A-C, Effect sizes indicate between-group differences. D, A reduced error pruning tree classify toddlers who had participated in both the techno and the traffic paradigms
classifier using 4 eye-tracking metrics (percent fixation on motherese from the techno (n = 430) as ASD (n = 283) or non-ASD (n = 147). ASD indicates autism spectrum
and traffic paradigms and saccades per second viewing motherese) was trained to disorder; TD, typical development; and TypSibASD, typical sibling of an ASD proband.

Figure 3. Saccade Profiles Stratified by Diagnostic Group

A Motherese vs techno B Motherese vs traffic

2.6 ASDLow Mthr Attn (n = 91) 2.6 ASDLow Mthr Attn (n = 67)
ASDMid Mthr Attn (n = 138) ASDMid Mthr Attn (n = 180)
2.4 ASDHigh Mthr Attn (n = 88) 2.4 ASDHigh Mthr Attn (n = 128)
ASD features (n = 26) ASD features (n = 26)
Motherese AOI, saccades/s

Motherese AOI, saccades/s

2.2 Delay (n = 53) 2.2 Delay (n = 70)

TD (n = 73) TD (n = 106)
2.0 TypSibASD (n = 10) 2.0 TypSibASD (n = 11)

1.8 1.8

1.6 1.6

1.4 1.4

1.2 1.2

1.0 1.0
0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6
Techno AOI, saccades/s Traffic AOI, saccades/s

Circles indicate the mean saccade rate and error bars indicate the standard error of the motherese attention; TD, typical development; and TypSibASD, typical sibling of an
mean. Toddlers with autism spectrum disorder (ASD) were additionally stratified based ASD proband.
on strength of preference for motherese. AOI indicates area of interest; Mthr Attn,

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

Association Between Motherese Fixation Levels, Social and Language Ability, and Age
Collapsed across all diagnostic groups as well as within the ASD group alone, percentage of time
fixating on motherese speech during the techno paradigm was significantly correlated with receptive
and expressive language ability, social affect scores, and the overall socialization domain score on the
Vineland scales (Pearson r range for toddlers with ASD: 0.30-0.48; P < .001). When toddlers with
ASD were stratified as having low, middle, or high levels of attention toward motherese speech,
significant differences in social and language abilities between the subtypes were observed. For
example, within the social domain, the mean (SD) Vineland score was 9.55 (1.78) points lower (Cohen
d, 0.79; P < .001) and the mean (SD) social affect total score was 4.73 (0.63) points higher (indicating
greater symptom severity) in the low motherese attention group than in the high motherese
attention group (Cohen d, −1.12; P < .001). Within the expressive and receptive language domains, t
scores were a mean (SD) of 16.03 (1.90) and 17.45 (1.84) points lower, respectively (expressive:
Cohen d, 1.26 [P < .001]; receptive: Cohen d, 1.42 [P < .001]) (Figure 4). Similar results were obtained
for the traffic paradigm (eFigure 9 in Supplement 1). Overall, there were inconsistent associations
between fixation on motherese and age across diagnostic groups and paradigms (eResults, eTable 4,
and eFigures 9 and 10 in Supplement 1).

Test-Retest Reliability
Percent fixation levels on motherese up to 1 year following initial testing were significantly correlated
in the traffic paradigm, with ICC values ranging from 0.38 to 0.77. Fixation values associated with
intervals greater than 1 year were significantly correlated only in the techno paradigm (ICC, 0.48;
P = .001) (eResults and eTable 5 in Supplement 1).

Discussion
The animated speech style known as motherese can be found across cultures and languages,60 is
evident between deaf mothers and their deaf children,61,62 and has even been noted to occur while
fetuses are still in the womb.63 Likely genetic, motherese is more than a speech style; it is a tool for
reciprocal engagement that enhances social and language development, with infants often matching
the fundamental frequencies and voice pitch of their mothers.64 Using gaze-contingent eye tracking
that allowed toddlers to control the images and sounds they heard, we found that similar to toddlers
who are typically developing or non–ASD delayed, the majority of toddlers with ASD attended to
motherese speech at high levels. In contrast, approximately 23% of toddlers with ASD showed low
levels of attention toward motherese speech, with some as low as 1% to 2%. This subgroup instead
preferred to listen to noises such as the sound of horns beeping and car engines during traffic. When
fixation levels on motherese were at or below 30%, the PPV and specificity across the motherese vs
traffic and motherese vs techno paradigms were high and ranged between 94% and 98%,
depending on the test. Given that the tests are engaging for toddlers, result in objective quantitation
of social and language attention, and require less than 5 minutes to complete, they may be useful as
a screening or diagnostic tool to identify toddlers in most need of immediate attention.
Our conservative selection of a cutoff value of 30% fixation or less on motherese was deliberate
to tune the tests to have high specificity and reduce false-positive results, which are unnecessarily
stressful for parents.57 There is often a tradeoff, however, between specificity and sensitivity, and this
deliberate tuning lowered sensitivity. The low sensitivity of the motherese-attention biomarkers and
other ASD biomarkers31 likely reflects the true clinical and biological heterogeneity inherent in
ASD.65-67 In terms of genetic findings, most single-gene sequence variations, such as in the Shank
gene family, are found in approximately 1% of children with ASD.68
There was also an association between level of attention to motherese speech and social and
language abilities, with children showing the lowest levels of interest in motherese speech also
having the lowest social and language abilities. This is not surprising given the association of
experience with brain development.25,69-72 Stratifying toddlers with ASD in the current study into

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

low, middle, and high levels of attention to motherese speech also highlighted the reverse
phenomenon: toddlers in the high–motherese attention group had receptive and expressive
language standard scores 17.45 and 16.03 points, respectively, above those of toddlers with ASD in
the low–motherese attention group as well as better social affect scores. Given that there are critical
periods for language development that extend across the first years of life,73 it may be even more
challenging for children with ASD in the low–motherese attention group to catch up once this critical
period has passed. At least 1 previous eye-tracking study74 showed that toddlers with ASD who paid
the least attention to social images at ages 1 to 3 years had greater symptom severity 5 to 9
years later.
Our data also suggest that the subgroup of the population with ASD and low attention to
motherese may be more homogeneous at some intermediate psychobiological level, thereby

Figure 4. Differences in Clinical Phenotype Among Toddlers With Autism Spectrum Disorder (ASD) With Low,
Middle, and High Attention to Motherese Speech During the Techno Paradigm

A Distribution of fixation levels among toddlers with ASD

0 10 20 30 40 50 60 70 80 90 100
Percent fixation

ASDLow Mthr Attn (n = 91) ASDMid Mthr Attn (n = 138) ASDHigh Mthr Attn

B Social symptom severity C Socialization

P <.001
20 90
P <.001

P <.001 P <.001
16
85
Vineland subdomain
ADOS SA total

12

80

75
4

0 70
ASDLow ASDMid ASDHigh ASDLow ASDMid ASDHigh
Mthr Attn Mthr Attn Mthr Attn Mthr Attn Mthr Attn Mthr Attn

D Expressive language E Receptive language

40 40 P <.001
P <.001

35 35

P <.001
Mullen T-score

Mullen T-score

30 30
P <.001

A, Dots indicate percent fixation values on motherese

25 25 for individual toddlers; whiskers, the range; and
triangle, the mean. B-E, Differences in standardized
20 20 test scores between subgroups. Results were similar
for the traffic paradigm (eResults and eFigure 9 in
Supplement 1). ADOS indicates Autism Diagnostic
15 15
ASDLow ASDMid ASDHigh ASDLow ASDMid ASDHigh
Observation Schedule; Mthr Attn, motherese
Mthr Attn Mthr Attn Mthr Attn Mthr Attn Mthr Attn Mthr Attn attention; and SA, social affect.

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

potentially justifying the use of this test to stratify the population with autism in future studies of
social attention and its correlates. A recent study27 revealed that toddlers with ASD who showed low
attention levels to motherese speech as a group had lower levels of neural functional activity in
classic speech-processing areas, such as the superior temporal gyrus, compared with other toddlers
with ASD who paid greater attention to motherese speech.
Our findings also revealed a dissociation between saccade rates depending on what toddlers
were looking at but only for the ASD subgroup that showed the lowest levels of attention to
motherese. These toddlers showed a greater number of saccades during the brief periods that they
viewed the motherese videos, possibly reflecting greater anxiety or challenges related to speech
processing.
Interestingly, the motherese vs flat affect paradigm was not effective as a diagnostic classifier,
showing only minimal between-group ASD vs TD differences. Given that null results are rarely
reported,75 we believed this was important to underscore. One reason may be related to the nature
of the flat affect video that contained an actress speaking in an unnatural computer-like voice that
caused several toddlers to smirk and may have artificially increased attention to this video. Indeed,
total looking time in the flat affect AOI was higher than in the nonmotherese contrast videos used in
the other paradigms.

Strengths and Limitations

This study has several strengths. These include comprehensive diagnostic and psychometric
evaluations conducted by licensed clinical psychologists blind to eye-tracking scores and the
inclusion of multiple contrast groups including toddlers with non-ASD delays, an essential
component for determining future clinical utility.
This study also has limitations. Given that the sample contained a combination of toddlers who
first failed a parent-report screen at well-infant checkups and general community referrals, a key
limitation relates to the unknown generalizability of the findings as a universal screening approach.

Conclusions
Overall, attention to motherese speech is a fundamental property of early development that can be
rapidly measured using eye tracking. In this diagnostic study, a cutoff level of 30% fixation or less on
motherese speech was accurate at identifying toddlers who were diagnostically classified as having
ASD. Identifying toddlers who show unusually low levels of attention to motherese speech is
potentially beneficial not only for early ASD screening, diagnosis, and prognosis but also for possible
therapeutic targets and may be a key pathway toward precision medicine.

ARTICLE INFORMATION
Accepted for Publication: December 19, 2022.
Published: February 8, 2023. doi:10.1001/jamanetworkopen.2022.55125
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Pierce K
et al. JAMA Network Open.
Corresponding Author: Karen Pierce, PhD, Department of Neurosciences, University of California San Diego,
8110 La Jolla Shores Dr, La Jolla, CA 92037 (kpierce@health.ucsd.edu).
Author Affiliations: Autism Center of Excellence, Department of Neurosciences, University of California San
Diego, La Jolla.
Author Contributions: Dr Pierce had full access to all the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Concept and design: Pierce, Courchesne.
Acquisition, analysis, or interpretation of data: All authors.

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

Drafting of the manuscript: Pierce, Zahiri.

Critical revision of the manuscript for important intellectual content: Pierce, Wen, Andreason, Courchesne, Barnes,
Lopez, Arias, Esquivel, Cheng.
Statistical analysis: Wen, Zahiri.
Obtained funding: Pierce, Courchesne.
Administrative, technical, or material support: Pierce, Andreason, Courchesne, Barnes, Lopez, Arias,
Esquivel, Cheng.
Supervision: Pierce, Courchesne.
Conflict of Interest Disclosures: Dr Pierce reported receiving an ACES innovation donation to support
eye-tracking research outside the submitted work. Drs Pierce and Zahiri reported having a pending patent through
the University of California San Diego that incorporates the motherese eye tracking tests. No other disclosures
were reported.
Funding/Support: This study was supported by grants R01MH118879, R01MH080134, and R01MH10446 from
the National Institute of Mental Health (Dr Pierce) and grant 1R01DC016385 from the National Institute on
Deafness and Other Communication Disorders (Drs Pierce and Courchesne).
Role of the Funder/Sponsor: The NIMH had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: We thank the pediatricians in San Diego, California, for their help in establishing our Get
SET Early autism detection program and the children and families in San Diego who participated in this study.

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SUPPLEMENT 1.
eMethods.
eFigure 1. Participation Flowchart
eFigure 2. Summary of Reasons for Exclusion
eFigure 3. Test Overlap and Intersection Plot
eFigure 4. Histograms Illustrating Distribution of Clinical Scores Across Diagnostic Groups
eFigure 5. Comparison of Motherese Fixation Levels Across Eye-Tracking Systems
eFigure 6. Preexperiment Dog-Cat Training Task
eResults.
eTable 1. Pairwise Comparisons of Diagnostic Group Differences Across Motherese Paradigms
eTable 2. Cross-tabulation Tables
eTable 3. Metrics of Diagnostic Accuracy with 95% CIs
eFigure 7. Motherese Fixations Levels Stratified by Sex
eFigure 8. Relationships Between Motherese Fixation Levels Across Motherese Paradigms
eTable 4. Correlations Between Motherese Fixation Levels and Social and Language Ability in the Techno and
Traffic Paradigms

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 JAMA Network Open | Pediatrics Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

eFigure 9. Differences in Clinical Phenotype Between Toddlers with Low, Middle, and High Attention to Motherese
Speech During the Traffic Paradigm
eFigure 10. Age-related Changes in Motherese Fixation Levels
eTable 5. Test-Retest Reliability
eReferences.

SUPPLEMENT 2.
Data Sharing Statement

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