Biological Psychiatry Global Open Science,
Год журнала:
2021,
Номер
2(4), С. 319 - 331
Опубликована: Окт. 22, 2021
Noninvasive
neuroimaging
is
a
powerful
tool
for
quantifying
diverse
aspects
of
brain
structure
and
function
in
vivo,
it
has
been
used
extensively
to
map
the
neural
changes
associated
with
various
disorders.
However,
most
techniques
offer
only
indirect
measures
underlying
pathological
mechanisms.
The
recent
development
anatomically
comprehensive
gene
expression
atlases
opened
new
opportunities
studying
transcriptional
correlates
noninvasively
measured
phenotypes,
offering
rich
framework
evaluating
pathophysiological
hypotheses
putative
Here,
we
provide
an
overview
some
fundamental
methods
imaging
transcriptomics
outline
their
application
understanding
disorders
neurodevelopment,
adulthood,
neurodegeneration.
Converging
evidence
indicates
that
spatial
variations
are
linked
normative
during
age-related
maturation
neurodegeneration
part
cell-specific
markers
expression.
Transcriptional
disorder-related
phenotypes
also
transcriptionally
dysregulated
genes
identified
ex
vivo
analyses
patient
brains.
Modeling
studies
demonstrate
patterns
involved
regional
vulnerability
spread
disease
across
brain.
This
growing
body
work
supports
utility
testing
about
molecular
mechanism
driving
disease-related
macroscopic
phenotypes.
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Май 26, 2020
Tau
is
a
hallmark
pathology
of
Alzheimer's
disease,
and
animal
models
have
suggested
that
tau
spreads
from
cell
to
through
neuronal
connections,
facilitated
by
β-amyloid
(Aβ).
We
test
this
hypothesis
in
humans
using
an
epidemic
spreading
model
(ESM)
simulate
spread,
compare
these
simulations
observed
patterns
measured
tau-PET
312
individuals
along
disease
continuum.
Up
70%
the
variance
overall
spatial
pattern
can
be
explained
our
model.
Surprisingly,
ESM
predicts
irrespective
whether
brain
Aβ
present,
but
regions
with
greater
burden
show
than
predicted
connectivity
patterns,
suggesting
role
accelerating
spread.
Altogether,
results
provide
evidence
communication
pathways
even
normal
aging,
process
accelerated
presence
Aβ.
Gene
expression
fundamentally
shapes
the
structural
and
functional
architecture
of
human
brain.
Open-access
transcriptomic
datasets
like
Allen
Human
Brain
Atlas
provide
an
unprecedented
ability
to
examine
these
mechanisms
in
vivo;
however,
a
lack
standardization
across
research
groups
has
given
rise
myriad
processing
pipelines
for
using
data.
Here,
we
develop
abagen
toolbox,
open-access
software
package
working
with
data,
use
it
how
methodological
variability
influences
outcomes
Atlas.
Applying
three
prototypical
analyses
outputs
750,000
unique
pipelines,
find
that
choice
pipeline
large
impact
on
findings,
parameters
commonly
varied
literature
influencing
correlations
between
derived
gene
other
imaging
phenotypes
by
as
much
ρ
≥
1.0.
Our
results
further
reveal
ordering
parameter
importance,
steps
influence
normalization
yielding
greatest
downstream
statistical
inferences
conclusions.
The
presented
work
development
toolbox
lay
foundation
more
standardized
systematic
transcriptomics,
will
help
advance
future
understanding
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Апрель 19, 2022
Abstract
A
growing
number
of
studies
have
used
stylized
network
models
communication
to
predict
brain
function
from
structure.
Most
focused
on
a
small
set
applied
globally.
Here,
we
compare
large
at
both
global
and
regional
levels.
We
find
that
globally
most
predictors
perform
poorly.
At
the
level,
performance
improves
but
heterogeneously,
in
terms
variance
explained
optimal
model.
Next,
expose
synergies
among
by
using
pairs
jointly
FC.
Finally,
assess
age-related
differences
coupling
across
human
lifespan.
decreases
magnitude
structure-function
with
age.
these
are
driven
reduced
sensorimotor
regions,
while
higher-order
cognitive
systems
preserve
local
Our
results
describe
patterns
cortex
how
this
may
change
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Авг. 10, 2022
Abstract
Numerous
brain
disorders
demonstrate
structural
abnormalities,
which
are
thought
to
arise
from
molecular
perturbations
or
connectome
miswiring.
The
unique
and
shared
contributions
of
these
connectomic
vulnerabilities
remain
unknown,
has
yet
be
studied
in
a
single
multi-disorder
framework.
Using
MRI
morphometry
the
ENIGMA
consortium,
we
construct
maps
cortical
abnormalities
for
thirteen
neurodevelopmental,
neurological,
psychiatric
N
=
21,000
participants
26,000
controls,
collected
using
harmonised
processing
protocol.
We
systematically
compare
multiple
micro-architectural
measures,
including
gene
expression,
neurotransmitter
density,
metabolism,
myelination
(molecular
vulnerability),
as
well
global
measures
number
connections,
centrality,
connection
diversity
(connectomic
vulnerability).
find
relationship
between
vulnerability
white-matter
architecture
that
drives
disorder
profiles.
Local
attributes,
particularly
receptor
profiles,
constitute
best
predictors
both
disorder-specific
morphology
cross-disorder
similarity.
Finally,
consistently
subtended
by
small
subset
network
epicentres
bilateral
sensory-motor,
inferior
temporal
lobe,
precuneus,
superior
parietal
cortex.
Collectively,
our
results
highlight
how
local
attributes
connectivity
jointly
shape
abnormalities.
Molecular Psychiatry,
Год журнала:
2024,
Номер
29(6), С. 1869 - 1881
Опубликована: Фев. 9, 2024
Abstract
Schizophrenia
is
a
prototypical
network
disorder
with
widespread
brain-morphological
alterations,
yet
it
remains
unclear
whether
these
distributed
alterations
robustly
reflect
the
underlying
layout.
We
tested
large-scale
structural
in
schizophrenia
relate
to
normative
and
functional
connectome
architecture,
systematically
evaluated
robustness
generalizability
of
network-level
alterations.
Leveraging
anatomical
MRI
scans
from
2439
adults
2867
healthy
controls
26
ENIGMA
sites
data
Human
Connectome
Project
(
n
=
207),
we
against
two
susceptibility
models:
(i)
hub
vulnerability,
which
examines
associations
between
regional
centrality
magnitude
disease-related
alterations;
(ii)
epicenter
mapping,
identifies
regions
whose
typical
connectivity
profile
most
closely
resembles
morphological
To
assess
specificity,
contextualized
influence
site,
disease
stages,
individual
clinical
factors
compared
that
found
affective
disorders.
Our
findings
show
schizophrenia-related
cortical
thinning
spatially
associated
hubs,
suggesting
highly
interconnected
are
more
vulnerable
Predominantly
temporo-paralimbic
frontal
emerged
as
epicenters
profiles
linked
schizophrenia’s
alteration
patterns.
Findings
were
robust
across
sites,
related
symptoms.
Moreover,
transdiagnostic
comparisons
revealed
overlapping
bipolar,
but
not
major
depressive
disorder,
suggestive
pathophysiological
continuity
within
schizophrenia-bipolar-spectrum.
In
sum,
over
course
follow
brain
emphasizing
marked
temporo-frontal
at
both
level
group
individual.
Subtle
variations
stages
suggest
interacting
pathological
processes,
while
patient-specific
symptoms
support
additional
inter-individual
variability
vulnerability
schizophrenia.
work
outlines
potential
pathways
better
understand
macroscale
inter-
The
intrinsic
dynamics
of
neuronal
populations
are
shaped
by
both
microscale
attributes
and
macroscale
connectome
architecture.
Here
we
comprehensively
characterize
the
rich
temporal
patterns
neural
activity
throughout
human
brain.
Applying
massive
feature
extraction
to
regional
haemodynamic
activity,
systematically
estimate
over
6000
statistical
properties
individual
brain
regions'
time-series
across
neocortex.
We
identify
two
robust
spatial
gradients
dynamics,
one
spanning
a
ventromedial-dorsolateral
axis
dominated
measures
signal
autocorrelation,
other
unimodal-transmodal
dynamic
range.
These
reflect
gene
expression,
intracortical
myelin
cortical
thickness,
as
well
structural
functional
network
embedding.
Importantly,
these
correlated
with
meta-analytic
activation,
differentiating
cognitive
versus
affective
processing
sensory
higher-order
processing.
Altogether,
findings
demonstrate
link
between
architecture,
cognition.