Tavassoli et al.

Molecular Autism (2019) 10:4

https://doi.org/10.1186/s13229-019-0255-7

RESEARCH Open Access

Sensory over-responsivity: parent report,

direct assessment measures, and neural
architecture
Teresa Tavassoli1, Anne Brandes-Aitken2, Robyn Chu3, Lisa Porter3, Sarah Schoen3,5, Lucy Jane Miller3,4,5,
Molly Rae Gerdes6, Julia Owen7, Pratik Mukherjee8 and Elysa J. Marco6,9,10*

Abstract
Background: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable
measures are needed to understand the biological underpinnings of these differences. This study aimed to define a
scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using
MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed
measurable differences in their white matter integrity.
Methods: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including
autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts
based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory
Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons,
based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest.
Results: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR.
The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three
white matter tracts showing decreased fractional anisotropy relative to children without AOR.
Conclusions: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation.
A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP
parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these
preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR.
Keywords: Sensory over-responsivity, Diffusion Tensor Imaging, Assessment, Neurodevelopmental disorder, autism,
Sensory processing disorder

Background primary subtypes: difficulties modulating sensory input,

Sensory processing dysfunction (SPD), manifests as diffi- difficulties discriminating sensory information, and diffi-
culty interpreting the sensory world in an adaptive way, culties with sensory-based motor control [3]. While
is common across children with neurodevelopmental these challenges can exist independently, they often
disorders (NDD), including children who meet the cat- co-occur. The Diagnostic and Statistical Manual-5
egorical label of autism spectrum disorder (ASD) [1, 2]. (DSM-5) now includes hyper- and hypo-reactivity to
Under the umbrella of SPD, there are three suggested sensory input (characteristic of sensory modulation) as a
core criteria for ASD, which has prompted additional
* Correspondence: [email protected] interest and focus on sensory modulation [4].
6
Department of Neurology, University of California San Francisco, San Previous research suggests that one aspect of sensory
Francisco, CA, USA
9
Department of Pediatrics, University of California San Francisco, San
modulation, sensory over-responsivity (SOR), occurs
Francisco, CA, USA most frequently in the auditory and tactile domains;
Full list of author information is available at the end of the article thus, these sensory domains are the focus of this

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 2 of 10

investigation [5]. We chose to focus on SOR given the brain structure than direct assessment [32]. Further-
distress associated with it [6]. Over-responsivity mani- more, a recent factor analysis in children with autism
fests as extreme adverse or avoidant responses to sen- spectrum disorder questions the research validity of the
sory stimulation, such as covering ears and running SSP’s current factor structure, suggesting that two ques-
from the room in response to a vacuum cleaner, blender, tions in particular are specific to AOR, which is one of
or automatic flushing toilet (auditory over-responsivity the two sensory domains highlighted in this current
(AOR)). In the tactile domain, sensory over-responsivity project [33]. With a more limited but specific SOR subset
modulation difficulties may manifest as refusal to wear of questions from the SSP, we aim to better assess the
clothing (particularly underwear), not liking to be phenotype between auditory and tactile over-responsivity
touched, and not wanting to touch certain materials, in this cohort of children with and without neurodevelop-
leading to significant household disruption and social mental challenges.
challenges (tactile over-responsivity (TOR)). We suggest that often parent report measures, the totals
We seek to investigate the structural underpinnings of and even some of the current subscales, coalesce a more
SOR to determine if there is a unique, architectural complex cluster of behavioral observations while direct as-
neural signature that can be used as a biomarker for sessment, such as the one included in this study, aims to
intervention. This study focuses on auditory assess a single sensory domain at a single point in time, in
over-responsivity (AOR) and tactile over-responsivity a controlled environment, on a singular processing ability
(TOR) in a broad neurodevelopmental cohort, taking a (sensory over-responsivity). Several sensory observation
Research Domain Criteria (RDoC)-inspired “sensory-- measures exist for young children such as the Sensory In-
first” approach [7]. The goal is to compare direct assess- tegration and Praxis Tests (SIPT), the Sensory Processing
ment and parent report measures of AOR and TOR in a Assessment for Young Children (SPA), the Tactile Defen-
pediatric cohort and to explore the neural architecture siveness and Discrimination Test-Revised (TDDT-R), and
of SOR in children across categorical diagnoses. the Infant Test of Sensory Functioning [34–38]. A previ-
ous study using the Sensory Processing-Three Dimen-
Characterizing sensory over-responsivity in children with sions: Assessment (SP-3D:A), a direct sensory modulation
neurodevelopmental disorders observation for individuals 3 to 21 years of age, identified
Sensory responsivity measures include parent reports, the most differentiating items for children, adolescents,
expert observation, and psychophysiological testing [8– and young adults with autism [5]. Moreover, previous
11]. Currently, parent report measures often assess work investigated reliability and validity but cut-off scores
sensory modulation but include a combination of modu- to enable categorization for clinical utility and direct re-
lation phenotypes as well as other aspects of sensory search group comparison have not yet been developed
processing [12–18]. The Sensory Processing-Three Di- [39, 40]. Hence, this study seeks to advance the field of
mensions: Inventory quantifies sensory domains (vision, sensory assessments by comparing the auditory and tactile
hearing, touch, and movement) by modulation and over-responsive items for children with neurodevelop-
discrimination, as well as sensory-based motor chal- mental disorders using parent report (SSP) and direct as-
lenges [19, 20]. The Sensory Sensitivity Questionnaire sessment (SP-3D:A) and by providing cut-off scores.
and the Sensory Experiences Questionnaire characterize While other observational measures focus on one sensory
sensory modulation specifically for children with ASD domain, the SP-3D:A is ideally suited for this task, as it
[21, 22]. The Sensory Profile (SP) has been validated includes characterizations of SOR in both auditory and
cross-culturally and across clinical cohorts using sensory tactile domains [9].
quadrant and section scoring methodology [15, 23–29].
The Short Sensory Profile (SSP), derived from the SP, Neural architecture of sensory processing to date
has been used to differentiate typically developing The neural architecture, both structural and functional, of
children from children with ASD [8, 16, 18, 30, 31]. The sensory processing in individuals with autism has been
SSP and other parent reports have made significant explored using a variety of techniques and paradigms
contributions to the research and clinical understanding including EEG, MEG, fMRI, MRS, and DTI [41–46]. This
of sensory dysfunction and have been instrumental for study focuses on refining our understanding of the
“trait-based” assessment. Although important for de- structural differences underlying auditory and tactile
scribing trait behavior, caregiver reports are subjective over-responsivity using DTI across neurodevelopmental
by nature and often affected by previous experience and conditions. Prior DTI work has characterized the neural
expectation. Consequently, while they are a critical com- underpinnings of sensory processing differences more
ponent of a thorough and appropriate clinical formula- broadly in children with ASD and SPD but has not taken
tion, they are less ideal for objective state assessment a more parsimonious approach [32, 45, 47]. For example,
and in previous work have shown less correlation with Chang et al. reported robust alterations of posterior white

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 3 of 10

matter microstructure in children with broadly defined Table 1 Participant demographics—experiment 1

SPD relative to typically developing children (TDC) [32]. TDC NDD p value
This investigation found strong correlations between frac- n = 128 n = 176
tional anisotropy (FA), a measure of microstructural integ- Age (years) 9.8 ± 2.9 8.9 ± 3.1 F = 6.02, p = .01
rity, and parent report and direct assessment measures of Gender (m/f) 66/62 111/65 F= 3.28, p = .07
tactile and auditory discrimination across all children. FSIQ* 111.9 ± 18.1 101.4 ± 16.3 F = 13.4, p < .001
However, direct assessment of sensory discrimination TDC typically developing children, NDD neurodevelopmental disorders, FSIQ
showed stronger and more continuous mapping to under- Full Scale IQ
lying white matter integrity than the parent report mea- *FSIQ available for UCSF and Seaver Autism Center cohorts only (TDC n = 66,
NDD n = 76)
sures. Additionally, in children with ASD, Pryweller et al.
reported decreased FA in the inferior longitudinal fascic-
ulus (ILF), which correlated directly with measures of cohort had an SPD designation from a community occu-
TOR (defensiveness), suggesting atypical connectivity be- pational therapist and/or a score in the “definite differ-
tween the limbic system and multisensory integration re- ence” range (< 2% probability) in one or more of the SP
gions [46]. This finding offers a preliminary explanation section scores.
for the dysregulated emotional valence applied to Participants in this Sensory Processing Disorder Con-
non-noxious tactile stimuli. While the current literature sortium project were recruited from the University of
has provided initial evidence for structural correlates of California, San Francisco (UCSF) Sensory Neurodevelop-
sensory processing dysregulation, further research is ment and Autism Program, the STAR Institute in Den-
needed to specify the existence of neural tracts associated ver, Colorado, and the Icahn School of Medicine at
with specific domains of sensory over-responsivity. This Mount Sinai in New York (Seaver Autism Center). All
approach will contribute to developing novel, targeted in- parents provided written consent on behalf of their chil-
terventions aimed at atypical structural connectivity in dren, while children provided informed assent in accord-
children with neurodevelopmental disorders. By assessing ance with each site’s institutional review board. Given
connectivity before and after trainings targeting the retrospective nature of this study, not all children
over-responsivity, we hope to be able to determine were administered all measures. All typically developing
whether applied interventions are indeed leading to meas- children in this collaborative cohort who had the speci-
urable change. But first, we need to know where to look fied assessment were included for establishing cut-off
and what to measure. This study is an initial foray in this scores; children who had both direct assessment using
next step. In this study, we hypothesize that direct assess- the SP-3D:A and parent report using SSP were included
ment of AOR and TOR will show strong inter-test agree- in the phenotype comparison (n = 235). Children from
ment with corresponding parental report behaviors in a the UCSF site received the Wechsler Intelligence Scale
NDD cohort and that sensory-first categorization using for Children-Fourth Edition to evaluate cognition. Chil-
direct assessment of AOR will identify a more succinct dren from the Seaver Autism Center received the
subset of white matter tracts than previously identified Wechsler Abbreviated Scale of Intelligence [51, 52].
using parent report.
Experiment 2: structural neural assessment of auditory
Methods over-responsivity
Demographics For structural Diffusion Tensor Imaging (DTI) analysis,
Experiment 1: direct auditory and tactile over-responsive we included 39 boys from UCSF who successfully com-
phenotyping pleted direct sensory assessment and neuroimaging as-
A total of 304 participants were enrolled in experiment sessment (ASD, n = 13 (mean age 11 ± 2 years); SPD, n = 8
1—128 typically developing children (TDC) and 176 (mean age 11 ± 1 year); and TDC, n = 18 (mean age 12 ± 1
children with NDD (see Table 1). The NDD group was year)) (see Table 2). Fifteen children scored above cut-off
composed of 100 children with SPD (55 female, age 8.5 for AOR. This cohort has been previously described in
± 3.0 years) and 76 children with ASD (10 female, age Chang et al. [32]. Due to a small sample size in the TOR
9.6 ± 3.0 years). ASD cohort inclusion included a com- cohort, only eight children met TOR cut-off and we con-
munity diagnosis of ASD, a score of ≥ 15 on the Social strained the DTI analysis to the auditory domain.
Communication Questionnaire (SCQ) and/or a score of
≥ 25 on the autism quotient (AQ), and a confirmed ASD Measures
classification with the Autism Diagnostic Observation Sensory phenotyping measures
Schedule, Second Edition (ADOS-2) [48–50]. Partici- Parent report: Short Sensory Profile Questionnaire
pants in the SPD and TDC groups scored below cut-off The SSP includes 38 items in which parents rate how
criteria on the AQ or SCQ. Participants in the SPD often their child shows a particular sensory behavior

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 4 of 10

Table 2 Participant demographics—experiment 2 retrieve plastic fish from a bucket of ice water. The follow-
AOR NO-AOR p value ing SOR behaviors during the game are given a score of 0
n = 15 n = 24 (not present) or 1 (observed): adverse response (0/1) (e.g.,
Age (years) 11.33 ± 1.11 11.74 ± 1.48 p = .37 startling during sounds, grimacing), discomfort, worries,
VCI 110.0 ± 19.43 113.7 ± 16.14 p = .53 and/or avoidance (0/1) (e.g., stating worries about the task,
PRI 109.2 ± 14.62 112.8 ± 12.23 p = .35 refusing to do it). For auditory over-responsive
VCI verbal comprehension index, PRI perceptual reasoning index, AOR above auditory
(SP-3D:AOR) and tactile over-responsive (SP-3D:TOR)
over-responsive cut score, NO-AOR below auditory over-responsive cut score composite scores, we summated the SOR behavior scores
for the three games. Behaviors observed during, not prior
using a five-point Likert scale ranging from always (1) to to, or between tasks are included. Thus, each composite,
never (5). Higher scores reflect more sensory-typical be- SP-3D:AOR and SP-3D:TOR, ranges from 0 to 6. A child
havior. To align with the SP-3D:A, we inverted the scor- who does not show any OR behaviors would score a 0,
ing with never (1) and always (5). Thus, higher scores on and a child who scores for adverse response (1) and avoid-
both parent report and direct assessment will reflect ance (1) on all three selected games would score a 6.
greater SOR. The SSP has high internal reliability
(.90–.95) and shows sensory differences in up to 90% of
DTI acquisition
children and adults with ASD compared to controls [8,
MR imaging was performed on a 3 T Tim Trio scanner
30]. To achieve an SOR-specific score for the auditory
(Siemens, Erlangen, Germany) using a 12-channel head
and tactile domains, we chose items reflecting SOR be-
coil with an axial 3D magnetization-prepared rapid ac-
haviors by clinical consensus (TT, EJM, SS, LJM, RC,
quisition gradient-echo T1-weighted sequence (TE =
LP) (see Table 3). We included items that represent clear
2.98 ms, TR = 2300 ms, TI = 900 ms, flip angle of 90°)
signs for SOR, rather than items that could be explained
with in-plane resolution of 1 × 1 mm on a 256 × 256
by other factors such as attention difficulties (e.g., we ex-
matrix and 160 1.0-mm contiguous partitions.
cluded auditory filtering items such as “Can’t work with
Whole-brain diffusion imaging was performed with a
background noise”).
multislice 2D single-shot twice-refocused spin
echo-planar sequence with 64 diffusion-encoding direc-
tions, diffusion-weighting strength of b = 2000 s/mm2,
Clinician-administered assessment: Sensory Processing-
iPAT reduction factor of 2, TE/TR = 109/8000 ms, NEX
Three Dimensions: Assessment
= 1, interleaved 2.2-mm-thick axial slices with no gap,
The SP-3D:A, a structured observational tool measuring
and in-plane resolution of 2.2 × 2.2 mm on a 100 × 100
behavioral response to specific sensory stimuli, includes
matrix. An additional image volume was acquired with
probes that are administered by a STAR Institute-trained,
no diffusion weighting (b = 0 s/mm2). The total diffusion
research-reliable experimenter. The internal reliability is
acquisition time was 8.7 min. Structural MRI for all chil-
high (alpha = .94) [9]. Here, we included three auditory
dren was reviewed by Dr. Pratik Mukherjee, a pediatric
probes: “Find a picture,” during which participants cross
neuroradiologist, blind to cohort assignment. No clinically
out symbols with loud background noise; “Orchestra
significant structural anomalies were identified.
time,” in which participants play along with loud music
using provided instruments; and “Sound and pictures,”
where participants identify sounds such as a vacuum DTI pre-processing
cleaner or dog barking. The tactile probes included the The diffusion-weighted images were corrected for
following: “Paint your arm,” during which participants motion and eddy currents using Functional Magnetic
paint their arm with a feather, a brush, and a rough Resonance Imaging of the Brain Software Library’s
sponge; “Goo,” in which participants remove two plastic Linear Image Registration Tool (FSL; FLIRT1) with
animals from goo; and “Fishing,” requiring participants to 12-parameter linear image registration [53]. All

Table 3 Short Sensory Profile items for tactile and auditory over-responsivity
SSP:TOR SSP:AOR
1. Expresses distress during grooming 34. Responds negatively to unexpected or loud noises
2. Avoids going barefoot, especially in sand or grass 35. Holds hands over ears to protect ears from sound
3. Reacts emotionally or aggressively to touch
4. Withdraws from splashing water
5. Has difficulty standing in line or close to other people
6. Rubs or scratches out a spot that has been touched
SOR sensory over-responsivity, SSP Short Sensory Profile, TOR tactile over-responsivity, AOR auditory over-responsivity

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 5 of 10

diffusion-weighted volumes were registered to the refer- Due to a small sample size in the tactile domain (n = 8),
ence b = 0 s/mm2 volume. To evaluate participant move- we focused on AOR for experiment 2. We analyzed mean
ment, we calculated a scalar parameter quantifying the FA differences in 22 bilateral ROIs. We constructed ANO-
transformation of each diffusion volume to the refer- VAs using the categorical predictor variable for AOR (two
ence. As reported in previous studies, 16 children were levels: above or below cut score), and the outcome vari-
excluded for DTI artifacts and/or median relative dis- ables were the 22 ROIs. We review these findings both
placement between volumes greater than 2 mm, where a with and without false detection rate (FDR) correction to
volume represents a single diffusion directional meas- p values (0.05) for each ANOVA test.
urement of the entire brain. This left a total of 39 chil-
dren with DTI datasets meeting quality control criteria Results
and direct assessment with the SP-3D:A. A heterosce- Experiment 1
dastic two-sample Student’s t test verified that there Cohort groupings based on the TDC results of parent
were no significant differences between these AOR and report and direct assessment measures were determined
TDC groups in movement during the DTI scan (p > (see Table 4 and Additional file 1: Figure S1, Add-
0.05). The non-brain tissue was removed using the Brain itional file 2: Figure S2, and Additional file 3: Figure S3).
Extraction Tool. FA was calculated using FSL’s DTIFIT Specifically, for each measure, we calculated the TDC
at every voxel, yielding FA maps for each participant. mean + 1 SD. We then, per mathematical convention,
rounded to the nearest whole integer (i.e., 1.3 would
Region of interest DTI analysis round down to 1 and 9.7 would round up to 10). The
Tract-Based Spatial Statistics in FSL was used to resulting number was used as the dividing line between
skeletonize and register the diffusion maps for each par- SOR and NO-SOR groups such that children who
ticipant in order to perform voxel-wise comparisons scored greater than the integer were placed in the SOR
along the white matter skeleton [54]. First, each partici- group while those scoring less than or equal to the value
pant’s FA map was non-linearly registered to each other were included in the NO-SOR group.
participant’s FA map to identify the most representative Using direct assessment, children were classified as
FA map as a registration target. The registered maps SP-3D:AOR or SP-3D:TOR if they scored 2 or above.
were then averaged and skeletonized to the center of the With these direct assessment cut-off scores, 31% of chil-
white matter. Next, each participant’s FA data was pro- dren with NDD were classified as having AOR and 27%
jected onto this mean skeleton to obtain skeletonized FA having TOR (Table 5 and Additional file 4: Tables S1–S3
maps per participant. Tract regions of interest (ROIs) for additional categorical information). Using the SSP
were created according to The Johns Hopkins University parent report, children were classified as SSP:AOR if
ICBM-DTI-81 White-Matter Labeled Atlas [55]. Right they scored 5 or above and SSP:TOR if they scored 11
and left hemisphere ROI tracts were highly correlated or above. Thus, using parent report, 62% of the children
(r ≥ .50, p ≤ .001); thus, an average diffusion value across with NDD were classified as having AOR, whereas 68%
right and left tracts was created for each participant. had TOR. The inter-test agreement between SSP and
SP-3D:A for AOR was 65% and TOR was 50%. Based on
Statistical analysis a two-proportion z test for SP-3D:AOR, SSP:AOR,
Experiment 1: cut score analysis and inter-test reliability SP-3D:TOR, and SSP:TOR, the NDD group was signifi-
SPSS 24 was used to analyze the SSP and SP-3D:A data. cantly more affected by SOR than the TDC group (χ2 ≥
Cut scores were designated at one standard deviation 17.5, p ≤ .0001).
above the TDC group’s mean (rounded to the nearest
whole integer) similar to the development of the Sensory Experiment 2
Experience Questionnaire cut-off scores [22]. Inter-rater The second aim of our study was to explore the neural
reliability was calculated by measuring the absolute mechanisms contributing to AOR based on direct
agreement between SSP:AOR and SP-3D:AOR and be-
Table 4 Cohort assignment for auditory and tactile over-
tween SSP:TOR and SP-3D:TOR. Chi-square analysis
responsivity
was used to assess differences in over-responsivity
TDC mean ± SD (n) + 1 SD NO-SOR SOR
between the NDD and TDC group.
SP-3D:A—auditory .38 ± .98 (127) 1.3 0–1 ≥2
Experiment 2: DTI analysis between children with and SP-3D:A—tactile .29 ± .72 (128) 1.0 0–1 ≥2
without auditory over-responsivity SSP—auditory 3.0 ± 1.4 (89) 4.4 2–4 ≥5
Utilizing the SP-3D:AOR cut score determined in ex- SSP—tactile 7.5 ± 2.2 (92) 9.7 6–10 ≥ 11
periment 1, we categorized the neuroimaging cohort to TDC typically developing children, SOR sensory over-responsivity, SP-3D:A
either an AOR (n = 15) or NO-AOR (n = 24) cohort. Sensory Processing-Three Dimensions: Assessment, SSP Short Sensory Profile

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 6 of 10

Table 5 Count and percentage of children with auditory or Table 6 DTI tracts showing decreased FA in the auditory over-
tactile over-responsivity responsive cohort
NDD TDC Tracts AOR vs. NO-AOR FA comparisons
SOR/total (% SOR) SOR/total (% SOR) Uncorrected p value (FDR-corrected p value)
SP-3D:AOR 55/176 (31) 13/127 (10) ICP .029 (.08)
SP-3D:TOR 48/176 (27) 9/128 (7) CP .023 (.08)
SSP:AOR 86/138 (62) 11/89 (12) ALIC .04 (.09)
SSP:TOR 97/143 (68) 8/92 (9) PTR .01 (.06)
Percentages reflect percent of children in their respective cohort meeting cut- ATR .03 (.08)
off criteria for SOR
SP-3D:A Sensory Processing-Three Dimensions: Assessment, SSP Short PCR .004 (.03)
Sensory Profile EC .03 (.08)
CGC .004 (.03)
assessment. We compared DTI tracts from children who SLF .003 (.03)
also completed the SP-3D:A. Based on our SP-3D:AOR IFOF .05 (.10)
cut score analysis, 15 children (3 TDC, 7 ASD, 5 SPD)
ILF .04 (.09)
met AOR threshold and 24 did not. The AOR and
This table displays group effects on Fractional Anisotropy. ICP inferior
NO-AOR cohorts did not differ in age (p = .37), percep- cerebellar peduncle, CP cerebral peduncle, ALIC anterior limb of the internal
tual IQ (p = .35), or verbal IQ (p = .53). We found that capsule, PTR posterior thalamic radiation, ATR anterior thalamic radiation, PCR
children with AOR had 11 total tracts showing de- posterior corona radiata, EC external capsule, CGC cingulate gyrus-cingular
portion, SLF superior longitudinal fasciculus, IFOF inferior fronto-occipital
creased FA relative to children without AOR. Given the fasciculus, ILF inferior longitudinal fasciculus. Bolded p values indicate
concern for multiple comparisons with this data-driven statistically significant effects after FDR correction
approach, we applied FDR correction and three tracts
continued to exceed the specified p value of < 0.05. provide a more reliable sensory cohort assignment and
These tracts are the posterior corona radiata (PCR), cin- that this combined assessment might be more robust for
gulate gyrus-cingulum portion (CGC), and superior lon- use with structural neuroimaging analysis. However, we
gitudinal fasciculus (SLF) ( see Table 6 and Fig. 1). found that the parent report questionnaire and direct
observation have only a moderate overlap. Specifically,
Discussion the agreement between SSP and SP-3D:A for AOR was
Sensory processing dysfunctions, specifically sensory 65% and TOR was 50%; in other words, 65% of children
over- and under-responsivity, are now part of the who met AOR criteria on the parent report also met cri-
DSM-5 criteria for ASD [4]. However, sensory process- teria on direct assessment and 50% of children who met
ing challenges are also reported in children with other TOR criteria on the parent report also met criteria on
categorical conditions including ADHD and it is the the direct assessment. This divergence in parent report
principle behavioral symptom for children with isolated versus direct assessment is similar to previous work
sensory processing disorder. This growing recognition showing moderate or limited agreement between a sen-
has motivated the need for better clinical and research sory questionnaire and direct observation [5, 19]. Tavas-
measures to characterize sensory processing. Here, in soli et al. found an inter-rater agreement between
line with the RDoC framework, we investigate SOR in questionnaire and observation of 74%; however, general
the auditory and tactile domains as a dimension inde- sensory processing was evaluated rather than auditory
pendent of clinical condition. We show that auditory and tactile over-responsivity [5]. Schoen et al. focused
and tactile over-responsivity can be quantified directly on SOR and reported a moderate correlation of .47,
for children with and without NDD and that direct as- similar to our findings [19]. In line with previous re-
sessment has moderate concordance with parent report ports, we find that more children meet SOR criteria
measures. Second, we report three neural tracts that based on parent report than on direct assessment in
differentiate children with AOR from those without in a both the auditory and tactile domains, suggesting that
pilot cohort, an exploratory result that needs to be con- the direct assessment may be a more stringent measure.
firmed in larger-scale follow-up studies. It is worth noting, however, that the rates of auditory
Development of reliable sensory tools, both parent re- and tactile challenge are similar in the NDD group
ports and direct assessments, is a critical step for re- within each measure format. We would expect the TDC
searchers and clinicians alike. We hypothesized that group percentiles to be similar and fixed as the grouping
AOR and TOR group assignment utilizing a combined method was based on their results. There are several
parent report/direct assessment methodology, similar to plausible explanations for the higher detection in parent
that used as gold standard diagnosis in ASD, would report than direct assessment. First, parent report is

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 7 of 10

Fig. 1 Skeletonized map of FA tracts. Image of the FA skeleton mask (green) displaying the tracts with significantly lower FA in the AOR group:
the bilateral posterior corona radiata (PCR, dark blue), superior longitudinal fasciculus (SLF, light blue), and the cingulate gyrus-cingulum portion
(CGC, red)

subjective due to parental bias and recollection bias. A has been shown to correlate better than parent report
second explanation for a broader catchment using par- for sensory discrimination, so it is not surprising that
ent report is that parents have more chances to observe the same could be found for sensory modulation
their child’s sensory reactivity symptoms across various over-responsive subtype [32]. We previously reported
environments; thus, a stable trait will be more evident. wide-spread differences in white matter microstructure
In a laboratory setting, the amount of sensory stimuli is in children with SPD and ASD relative to TDC [45].
controlled for and does not represent the vast amount of However, as we have reported in our somatosensory
sensory stimuli a child might experience in everyday sit- magnetoencephalography work, neural mechanisms can
uations. Therefore, parent reports likely reflect their often be better understood by splitting groups not by a
child’s atypical behavior across settings to be more abun- clinical label, such as ASD, but by a more narrow con-
dant than in the laboratory. Finally, it is possible that struct of interest, such as tactile sensitive versus tactile
parents of children with sensory and neurodevelopment typical [42]. Engaging a similar approach in this investi-
differences are more likely to rate their children as af- gation, we split our cohort not by traditional clinical
fected due to their additional knowledge and concern labels (ASD, SPD, or TDC) but by a direct measure
around aspects of atypical neurodevelopment. of AOR.
For clinical utility, we suggest using a combination of We conjectured that a sensory-first phenotype, in this
measures to identify children at risk, such as a sensory case AOR, allows for a more parsimonious identification
questionnaire and clinical assessment. We are not of key neural tracts. Indeed, in our previous work based
suggesting the use of the cohort assignment from this on parent report and a broad inclusion criteria for
research sample for clinical determination but rather to sensory processing dysfunction, we found decreased FA
assist in understanding of the currently available in children with SPD in the posterior body and isthmus
methods and tools. The goal is to detect all children of the corpus callosum, the left posterior thalamic radia-
who might have sensory modulation challenges that tions (PTR), left PCR, and the posterior aspect of the left
interfere with learning and social engagement and to be SLF [32]. Here, for children with AOR, the PCR, CGC,
able to clinically intervene as early as possible. For re- and SLF tracts showed decreased FA. In this analysis,
search purposes, however, we suggest the use of sensory the isthmus, posterior body of the corpus callosum, and
questionnaires as a screening tool, followed by standard- the PTR were not significantly different between AOR
ized direct observations. Quantitative direct observation and NO-AOR cohorts. While one might postulate that
measures should be used when investigating biological the current analysis was underpowered to detect the dif-
mechanisms. Future research with larger sample sizes ference, this is unlikely given that the original study had
and testing across multiple domains is needed to test 16 children in the general SPD group and 24 children in
these assumptions. Future research should explore the the TDC group, which is roughly similar to the 15 AOR
link between sensory questionnaires, observational mea- and 24 NO-AOR children in this present study. We sub-
sures, and psychophysiological measures of sensory mit, instead, that the PCR, SLF, and CGC may represent
perception. critical connections in an AOR network. Additional
With regard to the best method for revealing brain be- work in a larger sample that will allow for investigation
havior relationships, a more singular, direct assessment of TOR to determine if this network is a shared

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Tavassoli et al. Molecular Autism (2019) 10:4 Page 8 of 10

over-responsivity network or specific to the auditory do- standardization. In future studies, we hope to also move
main is needed. In addition, a larger sample will allow beyond group analysis to be able to study sensory
for comparisons of SOR architecture in children with over-responsivity as a continuum, which will not only
additional neurodevelopmental domains of challenges yield important insights into sensory challenges, but also
such as dysgraphia, dyspraxia, or sustained attention def- the sensory strengths that have been reported for many in-
icits. More broadly, this research adds to a growing body dividuals with autism such as enhanced visual search and
of literature associating the neural contributions of sen- auditory perception [57, 58].
sory over-responsivity.
Conclusions
Future directions and limitations
This study identified cut scores for AOR and TOR using
As with any study, there are limitations. First of all, the
both a parent report measure and direct observation.
gender distribution between the neurodevelopmental
The SSP parent report and SP-3D:A direct observation
and TDC group was different given the higher male to
ratings overlapped moderately for AOR and TOR. The
female ratio in autism. Moreover, for experiment 1,
direct observation measure here, the SP-3D:A, can be
groups were not matched on cognitive abilities or age.
used in clinical and research settings to augment SOR
Nevertheless, this should not have affected our analysis;
phenotyping and further investigate underlying mecha-
for experiment 1, we do not compare groups but rather
nisms of sensory modulation.
use the TDC values for SOR group assignment in the
NDD cohort. In experiment 2, the DTI analysis, sex, age,
and cognitive abilities were matched. Consequently, in- Additional files
vestigation in a cohort with both males and females is
essential. Second, although over 300 participants took Additional file 1: Figure S1. Auditory and tactile normative distribution
part in our first analysis, only 39 participants took part in the TDC cohort. Auditory over-responsivity on the SP-3D:A and SSP.
Tactile over-responsivity on the SP-3D:A and SSP (PDF 196 kb)
in the DTI imaging experiment. Consequently, the TOR
Additional file 2: Figure S2. Auditory and tactile normative distribution
group with neuroimaging available consisted of only in the ASD cohort. Auditory over-responsivity on the SP-3D:A and SSP.
eight children which were insufficient for statistical com- Tactile over-responsivity on the SP-3D:A and SSP (PDF 222 kb)
parison. For future SOR neuroimaging studies, a larger Additional file 3: Figure S3. Auditory and tactile normative distribution
in the SPD cohort. Auditory over-responsivity on the SP-3D:A and SSP.
group of children with mixed neurodevelopmental pro-
Tactile over-responsivity on the SP-3D:A and SSP (PDF 219 kb)
files will allow for a broader range of sensory function.
Additional file 4: Table S1. Percentage of children with auditory or
Furthermore, large and broad NDD cohorts will facili- tactile over-responsivity. Table S2. Children with over-responsivity at two
tate the understanding of whether SOR differences are standard deviations above the mean. Table S3. Sensory over-responsivity
fundamentally related to the current categorical cohorts scores by categorical group on direct and parent assessment (DOCX 23 kb)

such as ASD or SPD and whether sensory typical

children can be included in the continuum for neural Abbreviations
mapping. However, emerging genetic findings, imaging ADOS-2: Autism Diagnostic Observation Schedule, Second Edition;
AOR: Auditory over-responsivity; AQ: Autism quotient; ASD: Autism spectrum
reports, and even overlap in clinical semiology for indi-
disorder; DSM-5: Diagnostic and Statistical Manual-5; DTI: Diffusion Tensor
vidual children suggest that SOR will not respect these Imaging; FA: Fractional anisotropy; FDR: False detection rate; ILF: Inferior
clinical divisions. longitudinal fasciculus; NDD: Neurodevelopmental disorders; RDoC: Research
Domain Criteria; ROI: Region of interest; SCQ: Social Communication
Another limitation is that the cingulum bundle was di-
Questionnaire; SOR: Sensory over-responsivity; SP: Sensory Profile; SP-
vided into two portions, the superior and hippocampal 3D:A: Sensory Processing-Three Dimensions: Assessment; SPD: Sensory
region. While this is standard convention, reports that processing dysfunction; SSP: Short Sensory Profile; TDC: Typically developing
children; TOR: Tactile over-responsivity
suggest a finer parcellation of the CGC into retrosplenial
and subgenual divisions to better reflect the independent
connections should be considered [56]. Acknowledgements
We would like to thank Carly Demopoulos and Sam Payabvash for editorial
Future studies will need to include a larger cohort of in- review. We would also like to thank all the children and families for their
dividuals with and without neurodevelopmental concerns participation and support in our research.
to better understand other sensory phenotypes, such as
sensory under-responsivity (SUR) and sensory seeking. Funding
The current study is a first step in understanding the rela- This work was funded by grants from the Wallace Research Foundation to
EJM, TT, and to PM. It was also supported by gifts from the Mickelson and
tionship between parent and direct assessment and neural Brody Family Foundation, the Gates Family Foundation, the Gretsch Family
underpinnings of sensory over-responsivity using existing Foundation, and the Glass Family Foundation. EJM has also received
measures. The findings prompt the development of a neuroimaging support that contributed to this work from NIH K23MH083890.
We also received generous support from the SPD community of family and
more integrated parent and direct assessment battery as friends through gifts large and small to our UCSF Sensory Neurodevelopment
well as the development of a large normative dataset for and Autism Program (SNAP).

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Tavassoli et al. Molecular Autism (2019) 10:4 Page 9 of 10

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1
Department of Psychology and Clinical Language Sciences, University of springer.com/10.1007/s10803-009-0711-x.
Reading, Reading, UK. 2Department of Applied Psychology, New York 19. Schoen SA, Miller LJ, Green KE. Pilot study of the sensory over-responsivity
University, New York, NY, USA. 3Sensory Therapies and Research (STAR) scales: assessment and inventory. Am. J. Occup. Ther. 2008;62:393–406
Institute, Greenwood Village, CO, USA. 4University of Colorado Denver, Available from: http://www.ncbi.nlm.nih.gov/pubmed/18712002.
Denver, CO, USA. 5Rocky Mountain University of Health Professionals, Provo, 20. Schoen SA, Miller LJ, Sullivan J. The development and psychometric
UT, USA. 6Department of Neurology, University of California San Francisco, properties of the sensory processing scale inventory: a report measure of
San Francisco, CA, USA. 7Department of Radiology, University of Washington, sensory modulation. J Intellect Dev Disabil. 2017;42:12–21 Available from:
Seattle, WA, USA. 8Department of Radiology and Biomedical Imaging, https://www.tandfonline.com/doi/full/10.3109/13668250.2016.1195490.
University of California San Francisco, San Francisco, CA, USA. 9Department of 21. Minshew NJ, Hobson JA. Sensory sensitivities and performance on sensory
Pediatrics, University of California San Francisco, San Francisco, CA, USA. perceptual tasks in high-functioning individuals with autism. J. Autism Dev.
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Research Division, Cortica Healthcare, San Rafael, CA, USA. Disord. 2008;38:1485–98 Available from: http://link.springer.com/10.1007/
s10803-007-0528-4.
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