Abstract
Background
Sensory
over-responsivity
(SOR)
is
an
impairing
sensory
processing
challenge
in
autism
spectrum
disorder
(ASD)
which
shows
heterogenous
developmental
trajectories
and
appears
to
improve
into
adulthood
some
but
not
all
autistic
individuals.
However,
the
neural
mechanisms
underlying
interindividual
differences
these
are
currently
unknown.
Methods
Here,
we
used
functional
magnetic
resonance
imaging
(fMRI)
investigate
association
between
age
activity
linearly
nonlinearly
response
mildly
aversive
stimulation
as
well
how
SOR
severity
moderates
this
association.
Participants
included
52
ASD
(14F)
41
(13F)
typically
developing
(TD)
youth,
aged
8.6–18.0
years.
Results
We
found
that
pre-teens,
children
showed
widespread
activation
sensorimotor,
frontal
cerebellar
regions
compared
TD
children,
while
there
were
fewer
teens.
In
older
was
associated
with
less
prefrontal
cortex.
contrast,
more
engagement
of
integration
emotion
regulation
regions.
particular,
orbitofrontal
medial
cortices
a
nonlinear
relationship
ASD,
especially
steep
increase
sensory-evoked
during
mid-to-late
teen
There
also
interaction
youth
such
age-related
trends
apparent
higher
SOR.
Limitations
The
cross-sectional
design
limits
causal
interpretations
data.
Future
longitudinal
studies
will
be
instrumental
determining
co-develop
across
adolescence.
Conclusions
Our
results
suggest
enhanced
recruitment
may
underlie
decreases
for
subgroup
youth.
Molecular Psychiatry,
Год журнала:
2023,
Номер
28(5), С. 2158 - 2169
Опубликована: Март 29, 2023
Abstract
Individuals
with
autism
spectrum
disorder
(henceforth
referred
to
as
autism)
display
significant
variation
in
clinical
outcome.
For
instance,
across
age,
some
individuals’
adaptive
skills
naturally
improve
or
remain
stable,
while
others’
decrease.
To
pave
the
way
for
‘precision-medicine’
approaches,
it
is
crucial
identify
cross-sectional
and,
given
developmental
nature
of
autism,
longitudinal
neurobiological
(including
neuroanatomical
and
linked
genetic)
correlates
this
variation.
We
conducted
a
follow-up
study
333
individuals
(161
autistic
172
neurotypical
individuals,
aged
6–30
years),
two
assessment
time
points
separated
by
~12–24
months.
collected
behavioural
(Vineland
Adaptive
Behaviour
Scale-II,
VABS-II)
(structural
magnetic
resonance
imaging)
data.
Autistic
participants
were
grouped
into
clinically
meaningful
“Increasers”,
“No-changers”,
“Decreasers”
behaviour
(based
on
VABS-II
scores).
compared
each
subgroup’s
neuroanatomy
(surface
area
cortical
thickness
at
T1,
∆T
(intra-individual
change)
T2)
that
neurotypicals.
Next,
we
explored
differences’
potential
genomic
associates
using
Allen
Human
Brain
Atlas.
Clinical
subgroups
had
distinct
profiles
surface
baseline,
development,
follow-up.
These
enriched
genes
previously
associated
pathways
implicated
(e.g.
excitation-inhibition
systems).
Our
findings
suggest
outcomes
(i.e.
intra-individual
change
profiles)
core
symptoms
are
atypical
longitudinal,
i.e.
developmental,
profiles.
If
validated,
our
may
advance
development
interventions,
e.g.
targeting
mechanisms
relatively
poorer
outcomes.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Июнь 30, 2023
Autism
has
been
associated
with
differences
in
the
developmental
trajectories
of
multiple
neuroanatomical
features,
including
cortical
thickness,
surface
area,
volume,
measures
gyrification,
and
gray-white
matter
tissue
contrast.
These
neuroimaging
features
have
proposed
as
intermediate
phenotypes
on
gradient
from
genomic
variation
to
behavioral
symptoms.
Hence,
examining
what
these
proxy
markers
represent,
i.e.,
disentangling
their
molecular
underpinnings,
could
provide
crucial
insights
into
etiology
pathophysiology
autism.
In
line
this,
an
increasing
number
studies
are
exploring
association
between
neuroanatomical,
cellular/molecular,
(epi)genetic
autism,
both
indirectly
directly
vivo
across
age.
this
review,
we
aim
summarize
existing
literature
autism
(and
neurotypicals)
chart
a
putative
pathway
(i)
imaging-derived
(ii)
underlying
(neuropathological)
biological
processes,
(iii)
variation.
Genes,
Год журнала:
2021,
Номер
12(12), С. 2024 - 2024
Опубликована: Дек. 20, 2021
The
neuroanatomy
of
autism
spectrum
disorder
(ASD)
shows
highly
heterogeneous
developmental
trajectories
across
individuals.
Mapping
atypical
brain
development
onto
clinical
phenotypes,
and
establishing
their
molecular
underpinnings,
is
therefore
crucial
for
patient
stratification
subtyping.
In
this
longitudinal
study
we
examined
intra-
inter-individual
differences
in
the
trajectory
cortical
thickness
(CT)
childhood
adolescence,
genomic
33
individuals
with
ASD
37
typically
developing
controls
(aged
11-18
years).
Moreover,
aimed
to
link
regional
CT
intra-individual
variations
restricted
repetitive
behavior
(RRB)
over
a
two-year
time
period.
Individuals
showed
significantly
reduced
thinning
several
regions
functionally
related
wider
symptoms
traits
(e.g.,
fronto-temporal
cingulate
cortices).
spatial
patterns
neuroanatomical
were
enriched
genes
known
be
associated
at
genetic
transcriptomic
level.
Further,
correlated
within-subject
variability
severity
RRBs.
Our
findings
represent
an
important
step
towards
characterizing
underpinnings
based
upon
measures
CT.
our
provide
novel
insights
into
between
microscopic
macroscopic
pathology
ASD,
as
well
relationship
different
phenotypes.
Cell Calcium,
Год журнала:
2022,
Номер
104, С. 102582 - 102582
Опубликована: Апрель 10, 2022
Ca2+
signalling
is
of
prime
importance
in
controlling
numerous
cell
functions
the
brain.
Endolysosomes
are
acidic
organelles
currently
emerging
as
important
stores
astrocytes,
microglia,
endothelial
cells,
and
neurons.
In
neurons,
these
found
axons,
soma,
dendrites,
axon
endings
could
provide
local
sources
to
control
synaptic
transmission,
neuronal
plasticity,
autophagy
name
a
few.
This
review
will
address
how
recruited
response
stimulation.
We
focus
on
role
endolysosomal
two-pore
channels
(TPCs)
their
physiological
agonist
nicotinic
acid
adenine
dinucleotide
phosphate
(NAADP)
they
interact
with
cyclic
ADP-ribose
ryanodine
receptors
from
endoplasmic
reticulum.
Finally,
this
describe
new
pharmacological
tools
animal
mutant
models
now
available
explore
key
elements
brain
function
dysfunction.
Abstract
Background
Sensory
over-responsivity
(SOR)
is
an
impairing
sensory
processing
challenge
in
autism
spectrum
disorder
(ASD)
which
shows
heterogenous
developmental
trajectories
and
appears
to
improve
into
adulthood
some
but
not
all
autistic
individuals.
However,
the
neural
mechanisms
underlying
interindividual
differences
these
are
currently
unknown.
Methods
Here,
we
used
functional
magnetic
resonance
imaging
(fMRI)
investigate
association
between
age
activity
linearly
nonlinearly
response
mildly
aversive
stimulation
as
well
how
SOR
severity
moderates
this
association.
Participants
included
52
ASD
(14F)
41
(13F)
typically
developing
(TD)
youth,
aged
8.6–18.0
years.
Results
We
found
that
pre-teens,
children
showed
widespread
activation
sensorimotor,
frontal
cerebellar
regions
compared
TD
children,
while
there
were
fewer
teens.
In
older
was
associated
with
less
prefrontal
cortex.
contrast,
more
engagement
of
integration
emotion
regulation
regions.
particular,
orbitofrontal
medial
cortices
a
nonlinear
relationship
ASD,
especially
steep
increase
sensory-evoked
during
mid-to-late
teen
There
also
interaction
youth
such
age-related
trends
apparent
higher
SOR.
Limitations
The
cross-sectional
design
limits
causal
interpretations
data.
Future
longitudinal
studies
will
be
instrumental
determining
co-develop
across
adolescence.
Conclusions
Our
results
suggest
enhanced
recruitment
may
underlie
decreases
for
subgroup
youth.
