Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight
Nature reviews. Neuroscience,
Journal Year:
2023,
Volume and Issue:
24(10), P. 620 - 639
Published: Aug. 24, 2023
Language: Английский
Local molecular and global connectomic contributions to cross-disorder cortical abnormalities
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Aug. 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.
Language: Английский
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
29(6), P. 1869 - 1881
Published: Feb. 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-
Language: Английский
Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Jan. 21, 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
patients
26
controls,
collected
using
harmonized
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
that
regional
vulnerability
macroscale
network
architecture
interact
drive
spatial
patterning
disorders.
Local
attributes,
particularly
receptor
profiles,
constitute
best
predictors
both
disorder-specific
morphology
cross-disorder
similarity.
Finally,
consistently
subtended
by
small
subset
epicentres
bilateral
sensory-motor,
medial
temporal
lobe,
precuneus,
superior
parietal
cortex.
Collectively,
our
results
highlight
how
local
biological
attributes
connectivity
jointly
shape
abnormalities.
Language: Английский
Multimodal, multiscale connectivity blueprints of the cerebral cortex
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Dec. 2, 2022
The
brain
is
composed
of
disparate
neural
populations
that
communicate
and
interact
with
one
another.
Although
fiber
bundles,
similarities
in
molecular
architecture,
synchronized
activity
all
represent
connectivity,
a
comprehensive
study
how
these
connectivity
modes
jointly
reflect
structure
function
remains
missing.
Here
we
systematically
integrate
seven
multimodal,
multiscale
profiles
derived
from
gene
expression,
neurotransmitter
receptor
density,
cellular
morphology,
glucose
metabolism,
haemodynamic
activity,
electrophysiology.
We
uncover
compact
set
universal
organizational
principles
through
which
geometry
neuroanatomy
shape
emergent
modes.
Connectivity
also
exhibit
unique
diverse
connection
patterns,
hub
profiles,
dominant
gradients,
modular
organization.
Throughout,
observe
consistent
primacy
modes—namely
correlated
expression
similarity—that
map
well
onto
multiple
phenomena
including
the
rich
club
patterns
cortical
abnormalities
across
13
neurological,
psychiatric,
neurodevelopmental
disorders.
Finally,
fuse
into
single
multimodal
network
show
it
maps
major
features
structural
conenctivity,
intrinsic
functional
networks,
cytoarchitectonic
classes.
Altogether,
this
work
contributes
to
next-generation
connectomics
integrative
inter-regional
relationships.
Language: Английский
Reduced brain structural similarity is associated with maturation, neurobiological features, and clinical status in schizophrenia
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 26, 2024
Abstract
Schizophrenia
spectrum
disorders
(SSD)
are
characterized
by
atypical
brain
maturation,
including
reduced
structural
similarity
between
regions.
However,
the
maturational
and
neurobiological
underpinnings
of
complex
interactions
abnormal
development
network
reorganization
remain
poorly
characterized.
Using
MRI
data
from
195
healthy
controls
(HC)
352
individuals
with
SSD,
we
constructed
individual
Morphometric
INverse
Divergence
(MIND)
networks.
Compared
to
HC,
SSD
exhibited
in
temporal
cingulate
lobes,
more
pronounced
reductions
exhibiting
a
‘poor’
clinical
status
(more
impaired
cognitive
functioning
severe
symptomatology).
These
alterations
MIND
networks
were
associated
cortical
hierarchy
events,
locating
higher-order
association
areas
that
predominantly
mature
later.
Finally,
mapped
46
features
onto
revealing
high
presence
neurotransmitters,
astrocytes,
microglia,
along
decreased
metabolism
microstructure,
regions
SSD.
Taken
together,
these
findings
provide
evidence
on
interplay
dysconnectivity,
underlying
neurobiology
determining
Language: Английский