Figure 6: MRCPs show differences as a function the
preceding sensory cue. (A) SCPs contrasting ASD and TD participants
separately for each cue type (AV, A, V). (B-D) Topographic
visualizations of MRCPs plotted separately for TD (left) and ASD
participants (right) averaged across a 50 ms time bins. (B) -250 to -200
ms before the button press response. (C) -200 to -150 ms before the
button press response. (D) -100 to -50 before the button press. (E-F)
Grand average waveforms plotted separately for TD (left) and ASD
participants (right), stratified by the sensory cue type preceding the
motor response (AV, A, V). (E) Mid-frontal electrode Fz. (F) Left
parietal electrode P3.
Discussion
In this study, neural activity related to the generation of a cued motor
movement was investigated in children with ASD and matched typically
developing children using a simple speeded response task. Strengths of
the study included the simplicity of the task which allowed for the
investigation of basic sensorimotor processes, and the large sample size
(n=84 per group) of children with similar age, sex, and IQ, allowing for
the investigation of population differences with small and medium effect
sizes. The inclusion of children and adolescents across a wide age range
allowed for a cross-sectional investigation of sensorimotor processing
through different phases of child development.
Evidence of earlier ramp-up of sensory-cued motor preparation in TD
participants relative to ASD participants was shown over frontal and
parietal scalp regions (Figure 3 ), and slower reaction times in
ASD participants relative to TD were seen across all age ranges and
sensory cue types (Figure 2 ). Across both participant groups,
modulation in motor-related cortical potential (MRCP) morphology by
reaction time was observed (Figure 4 ). Between-group
differences in the topography and morphology of motor-related potentials
were most prominent in the youngest group of participants
(Figure 5 ). Differences in sensorimotor processes were also
evident as a function of sensory cue type, with multisensory
audio-visual stimuli evoking the highest-amplitude MRCPs and the
strongest between-group differences between ASD and TD participants
(Figure 6 ).
Participants with ASD showed poorer task performance than TD
participants. When considering all trials, slower response time was
observed in ASD participants. However, when analysis was constrained to
remove trials with excessively fast or excessively slow RTs (TD: 4.48%
of trials, ASD: 7.74%), significant between-group differences in mean
RT were observed only in the slowest quartile of trials, although ASD
participants continued to show greater RT variability. The current data,
showing lower response rates in ASD (ASD: 86.3% hit rate; TD: 92.7%
hit rate) coupled with greater RT variability support the idea that
lower task performance in ASD may be driven by a greater tendency toward
distractibility (Murphy et al., 2014). These data further suggest that
ASD-related motor slowing—a common finding across many behavioral
tasks (An et al., 2018; Sokhadze et al., 2016)—may be driven by a
minority (< 10%) of extremely slow responses.
Evaluation of group differences between ASD and TD participants for
three well-characterized MRCP components—the late berescheftspotential
potential (BP), motor potential (MP), and reafferent potential
(RAP)—revealed effects of diagnosis on sensorimotor processing across
all components in various parcellations of the MRCP data, but consistent
differences across all parcellations were observed in the late BP
period. Previous research has shown reductions in amplitude of the late
BP in patients with motor impairments, although previous work has
largely focused on individuals with cerebellar lesions (Kitamura et al.,
1999; Shibasaki et al., 1986) and focal hand dystonia (Deuschl et al.,
1995; Toro et al., 2000; Yazawa et al., 1999). In patients with focal
dystonia, BP amplitude reductions are suspected to arise due to
abnormalities in primary motor cortex function, as suggested by early
animal work. Evidence from early studies monitoring motor cortex
activation in cats during voluntary movement indicate that pyramidal
neurons located in the lateral motor cortex alter their firing rate
within 500 ms of a voluntary movement: a time-window consistent with the
late BP (Neafsey et al., 1978). In adults with cerebellar lesions, it is
hypothesized that late BP dysfunction is caused by a deficit of
facilitatory input from the cerebellum to these BP-generators in the
lateral premotor cortex (Kitamura et al., 1999; Shibasaki and Hallett,
2006). In the Autism literature, the cerebellum has consistently emerged
as a region showing both functional (Unruh et al., 2019) and
morphological alterations (Mapelli et al., 2022). For example, post
mortem examinations have identified ASD-related reductions in Purkinje
cell size (Fatemi et al., 2002) and number (Kemper and Bauman, 1993).
While cerebellar contributions to altered sensorimotor activity cannot
be assessed under the current design and methodological approach, data
from functional neuroimaging show hyperactivation of the cerebellum in
ASD participants during a precision grip task, suggesting functional
reorganization of motor systems which emphasizes subcortical processes
(Unruh et al., 2019). Disrupted processing in this network could
conceivably contribute to the more variable reaction times and altered
sensorimotor processing uncovered by the current work.
For both participant groups, modulation of MRCPs by response speed was
observed, with fast trials showing higher-amplitude activity during the
late BP period occurring prior to the button-press response. However,
the strongest differences between ASD and TD participants were observed
in later phases of the MRCP surrounding the MP (0-25ms post-response).
While modulation of motor potentials as a function of numerous
task-related features such as task complexity (Mussini et al., 2021) and
attention (Aliakbaryhosseinabadi et al., 2017) have been shown
previously, the current results implicate response promptness as an
additional modulatory factor. Although modest statistical differences
were observed between ASD and TD participants, primarily in the fastest
50% of trials, largely similar topographic maps indicate recruitment of
similar generators.
Differences in MRCP amplitude were also observed as a function of the
preceding sensory cue type. Although event-related time-locking to the
button-press response allows for examination of motor-related effects,
movement execution in response to a sensory cue necessitates processing
of that sensory cue. The current data, showing the largest between-group
differences in the multisensory condition, accords with findings from a
previous analysis of a subset of the current data showing
higher-amplitude sensory-evoked responses to multisensory stimuli (AV)
compared to unisensory stimuli (A or V) (Brandwein et al., 2013),
underscoring the overlap of sensory processing and motor preparation in
the context of a cued-motor paradigm. While between-group differences in
MRCPs were present for all three cue types, differences between ASD and
TD waveforms were greatest in the multisensory condition. This latter
finding is consistent with neurophysiological findings that multisensory
(here, audio-visual) inputs are processed differently in ASD compared to
TD (Beker et al., 2018; Brandwein et al., 2013; Foxe et al., 2015; Russo
et al., 2010) and may also reflect that ASD/TD differences in
multisensory integration extend beyond the sensory processing stage into
stages more classically associated with motor planning (Mercier et al.,
2015).
Clear age-related differences in
MRCP morphology were observed. In TD participants, these age-related
differences were largely restricted to the post-response period while in
ASD participants, additional differences were evident in the
pre-response period beginning approximately 250 ms prior. Literature on
the maturation of sensorimotor preparatory and post-movement processing
is sparse. However, the current data would suggest that, in TD
individuals, maturation effects in motor processes are most prominent in
the RAP period (90-130 ms after movement onset) associated with
somatosensory feedback processing. For ASD participants, maturation
effects extend across the MRCP, spanning both the late BP and
post-response periods. Between-group differences in MRCP maturation were
most pronounced in younger participants. These data suggest ongoing
maturation of the late BP in children with Autism and that early
sensorimotor processes remain largely stable in TD children after age 6.
These data are consistent with clinical reports of delayed fine motor
skill acquisition in ASD relative to TD individuals (Fournier et al.,
2010).
Finally, it should be noted that, while statistical differences between
ASD and TD participants were visible across most parcellations of the
current neural and behavioral data–such as when responses were binned
by age, response promptness, and the preceding sensory cue type–these
basic sensorimotor differences are unlikely to represent a sole
explanation of the extensive and often severe motor impairment commonly
reported in ASD (Green et al., 2009). Indeed, in the current work, the
general topographic similarities of MRCPs between groups (Figure
3-6 ) suggest that processes upstream and downstream of sensorimotor
preparation which were not examined in the current work—such as
action-selection, motor sequence learning, or social communication—
very likely also contribute to overall motor-related difficulties.
Previous work has consistently demonstrated that individuals with ASD
show neural and behavioral atypicalities when engaging in the high-level
processes of movement imitation and pantomiming, indicating a breakdown
of sensory integration, motor processing, social communication, or an
interaction between all three variables. In neurotypical adults, for
example, mu-band neuroscillitory suppression was shown to occur during
both observed movements and self-initiated movements, whereas adults
with ASD only showed such suppression during self-movement (Bernier et
al., 2007; Oberman et al., 2005). While differences in sensorimotor
processing were shown in the current work using a non-social task, it
seems plausible that these differences may be exacerbated by tasks which
additionally require the recruitment of higher-level cognitive
processes. For example, in a motor response task to assess
action-consequence learning in children with ASD, researchers observed
differential modulation of the late BP component between groups (Migó et
al., 2021). Children with ASD showed an enhanced late BP component
during task segments in which a button press response was associated
with an auditory consequence whereas, in contrast, TD participants
showed an enhanced BP when the press did not result in a
consequence. Although caution must be taken in generalizing from these
relatively small sample studies, these data may reflect that basic
differences in motor processing and preparation are mediated by
cognitive factors such as the perceived meaningfulness of the generated
movement or its social context.
This study is not without limitations. Although the quick and variable
interstimulus interval used in the current investigation allowed for the
presentation of a large number of trials (972 ± 58 trials per
participant), the rapidity with which stimuli were presented precluded
investigation of group differences in the early BP component onsetting
between 1 and 3 seconds prior to the response. Further, although
response-locked averaging is a common and well-documented approach for
MRCP analysis, electromyographic (EMG) data monitoring skeletal muscle
contraction prior to the response were not recorded in the current
study, and therefore EMG-locked analyses could not be performed.
Further, for the majority of participants, clinical assessments of
attention deficit hyperactivity disorder (ADHD) and associated symptoms
were not conducted. An investigation of the relationship between
observed sensorimotor differences and symptoms of ADHD—a common
comorbidity in ASD—is therefore outside the scope of the current work.
While the broad age range in the current work included children as young
as 6 years old, more work is needed to understand the neural trajectory
of early sensorimotor development (e.g. in children 6 months to 5
years).
In summary, the current investigation presented data on the development
of the MRCP in healthy children and adolescents, and evidence of
moderate alteration in sensorimotor processes in children with ASD
relative to typically developing peers. These data suggest that subtle
sensorimotor atypicalities are present in non-social contexts and that
these differences are most prominent in the youngest group of children
(age 6-9). Future studies focused
on younger children are still needed to understand the early development
of sensorimotor processes in autism. Additionally, work examining
movement imitation in ASD may consider the role of basic motor responses
when interpreting between-group differences using more complex tasks.
Author Contributions: SM and JJF designed the original
experiment. All authors conceived of the current study. KMW analyzed the
data in consultation with SM and JJF. KMW produced the figures for this
study. KMW wrote the first draft of the manuscript, and all authors
provided editorial input on subsequent drafts. All authors read and
approved the final version of this manuscript.
Acknowledgements : The authors thank Douwe Horsthuis for
assistance with data collection and the Human Clinical Phenotyping Core
(HCP) for their careful clinical and cognitive phenotyping of our ASD
cohort.
Conflict of Interest : The authors report no conflict of
interest, financial or otherwise.
Ethics and Consent : The institutional review board at Albert
Einstein College of Medicine and the City College of New York approved
all experimental procedures. Each participant provided written informed
consent in accordance with the tenets laid out in the declaration of
Helsinki.
Funding Information : This work was supported by the National
Institute of Mental Health of the National Institutes of Health (NIH)
under award number R01MH085322 (S.M. and J.J.F.), and the Eunice Kennedy
Shriver National Institute of Child Health & Human Development of the
NIH under award number P50 HD105352 (Rose F. Kennedy Intellectual and
Developmental Disabilities Research Center). Funding for KMW was
provided through the Rose F. Kennedy Intellectual and Developmental
Disabilities Research Center (T32 HD0980676). Ongoing work on Autism
Spectrum Disorder (ASD) at The University of Rochester (UR)
collaborating site is supported by the UR Intellectual and Developmental
Disabilities Research Center (UR-IDDRC), through a center grant from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD P50 HD103536 to JJF).