bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 2, 2023
ABSTRACT
Interictal
spikes
(IIS)
and
seizures
are
well-documented
in
Alzheimer’s
disease
(AD).
IIS
typically
outnumber
seizures,
supporting
their
role
as
a
prominent
EEG
biomarker
AD.
In
preclinical
models,
we
showed
that
high
frequency
oscillations
(HFOs>250Hz)
also
occur,
but
it
is
currently
unknown
how
HFOs
compare
to
IIS.
Therefore,
asked
whether
the
incidence
of
differed
if
they
differentially
affected
by
behavioral
state.
We
used
three
mouse
lines
simulate
aspects
AD:
Tg2576,
presenilin
2
knockout,
Ts65Dn
mice.
recorded
quantified
hippocampus
during
wakefulness,
slow-wave
sleep,
rapid
eye
movement
sleep.
all
lines,
were
more
frequent
than
High
numbers
correlated
with
fewer
IIS,
suggesting
for
first
time
possible
competing
dynamics
among
them
Notably,
occurred
states
summary,
most
abundant
abnormality
when
compared
states,
better
These
findings
pertained
which
important
because
different
show
may
inhibit
SHORT
SUMMARY
common
occur
earlier
stages.
comparison
between
lacking.
Here
3
AD
features
local
field
potential
recordings
quantify
HFOs.
found
outnumbered
total
inversely
abnormality,
this
was
generalizable
across
types
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 6, 2025
Abstract
Hippocampal
sharp-wave
ripples
(SPW-Rs)
are
high-frequency
oscillations
critical
for
memory
consolidation
in
mammals.
Despite
extensive
characterization
rodents,
their
application
as
biomarkers
to
track
and
treat
dysfunction
humans
is
limited
by
coarse
spatial
sampling,
interference
from
interictal
epileptiform
discharges
(IEDs),
lack
of
consensus
on
human
SPW-R
localization
morphology.
We
demonstrate
that
mouse
hippocampal
share
spatial,
spectral
temporal
features,
which
clearly
distinct
IEDs.
In
1024-channel
recordings
APP/PS1
mice,
SPW-Rs
were
distinguishable
IEDs
narrow
the
CA1
pyramidal
layer,
narrowband
frequency
peaks,
multiple
ripple
cycles
unfiltered
local
field
potential.
epilepsy
patients,
showed
similar
peaks
visible
subiculum
but
absent
dentate
gyrus.
Conversely,
a
broad
extent
wide-band
power.
introduce
semi-automated,
detection
toolbox
(“ripmap”)
selecting
optimal
channels
separating
event
waveforms
low-dimensional
embedding.
Our
approach
improves
accuracy,
providing
firm
foundation
future
research.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Nov. 2, 2023
The
mechanisms
that
confer
cognitive
resilience
to
Alzheimer's
Disease
(AD)
are
not
fully
understood.
Here,
we
describe
a
neural
circuit
mechanism
underlying
this
in
familial
AD
mouse
model.
In
the
prodromal
disease
stage,
interictal
epileptiform
spikes
(IESs)
emerge
during
anesthesia
CA1
and
mPFC
regions,
leading
working
memory
disruptions.
These
IESs
driven
by
inputs
from
thalamic
nucleus
reuniens
(nRE).
Indeed,
tonic
deep
brain
stimulation
of
nRE
(tDBS-nRE)
effectively
suppresses
restores
firing
rate
homeostasis
under
anesthesia,
preventing
further
impairments
nRE-CA1
synaptic
facilitation
memory.
Notably,
applying
tDBS-nRE
phase
young
APP/PS1
mice
mitigates
age-dependent
decline.
IES
correlates
with
later
impairments.
findings
highlight
as
central
hub
functional
underscore
clinical
promise
DBS
conferring
pathology
restoring
circuit-level
homeostasis.
Advances in psychology, mental health, and behavioral studies (APMHBS) book series,
Journal Year:
2025,
Volume and Issue:
unknown, P. 33 - 64
Published: Jan. 3, 2025
Advancements
in
artificial
intelligence
(AI)
are
revolutionizing
neurophysiology,
enhancing
precision
and
efficiency
assessing
brain
nervous
system
function.
AI-driven
neurophysiological
assessment
integrates
machine
learning,
deep
neural
networks,
advanced
data
analytics
to
process
complex
from
electroencephalography,
electromyography
techniques.
This
technology
enables
earlier
diagnosis
of
neurological
disorders
like
epilepsy
Alzheimer's
by
detecting
subtle
patterns
that
may
be
missed
human
analysis.
AI
also
facilitates
real-time
monitoring
predictive
analytics,
improving
outcomes
critical
care
neurorehabilitation.
Challenges
include
ensuring
quality,
addressing
ethical
concerns,
overcoming
computational
limits.
The
integration
into
neurophysiology
offers
a
precise,
scalable,
accessible
approach
treating
disorders.
chapter
discusses
the
methodologies,
applications,
future
directions
assessment,
emphasizing
its
transformative
impact
clinical
research
fields.
Neuropsychopharmacology Reports,
Journal Year:
2025,
Volume and Issue:
45(1)
Published: Feb. 5, 2025
ABSTRACT
Aims
Alzheimer's
disease
(AD)
is
a
leading
cause
of
dementia,
with
increasing
prevalence.
Mutations
in
genes
like
MAPT,
PSEN1,
and
PSEN2
are
risk
factors,
to
the
development
several
AD
model
mice.
Recent
hypotheses
suggest
brain
pathology
involves
abnormal
neurodevelopment,
decreased
pH,
neural
hyperexcitation.
However,
it
remains
unclear
what
extent
these
pathologies
reflected
gene
expression
changes
models.
This
study
aims
compare
patterns
brains
multiple
mice
those
related
three
evaluating
overlap.
Methods
We
conducted
comprehensive
search
public
databases,
collecting
20
datasets
from
hippocampus
These
were
compared
sets
hippocampal
maturation,
hyperexcitation
statistically
assess
Pathway
enrichment
analysis
explored
biological
relevance
changes.
Results
The
overlap
maturity‐,
pH‐,
hyperexcitation‐associated
varied
across
models,
showing
significant
correlations
between
lower
maturity,
increased
In
MAPT
mutant
APP+PSEN1
homozygous
transgenic
mice,
signatures
became
more
pronounced
age.
meta‐analysis
revealed
that
associated
models
involved
synaptic
channel
functions,
as
well
inflammatory
responses,
consistent
previous
studies.
Conclusion
findings
pathophysiological
play
varying
roles
individual
Our
recent
found
negative
correlation
progression
actual
pH
levels
human
patients.
Considering
results
presented
this
study,
maturity
hyperexcitation,
which
correlated
may
also
be
linked
progression.
Thus,
factors
could
useful
markers
for
assessing
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(33)
Published: Aug. 6, 2024
Brain
rhythms
provide
the
timing
for
recruitment
of
brain
activity
required
linking
together
neuronal
ensembles
engaged
in
specific
tasks.
The
γ-oscillations
(30
to
120
Hz)
orchestrate
circuits
underlying
cognitive
processes
and
working
memory.
These
oscillations
are
reduced
numerous
neurological
psychiatric
disorders,
including
early
decline
Alzheimer's
disease
(AD).
Here,
we
report
on
a
potent
brain-permeable
small
molecule,
DDL-920
that
increases
improves
cognition/memory
mouse
model
AD,
thus
showing
promise
as
class
therapeutics
AD.
We
employed
anatomical,
vitro
vivo
electrophysiological,
behavioral
methods
examine
effects
our
lead
therapeutic
candidate
molecule.
As
novel
central
nervous
system
pharmacotherapy,
molecule
acts
potent,
efficacious,
selective
negative
allosteric
modulator
γ-aminobutyric
acid
type
A
receptors
most
likely
assembled
from
α1β2δ
subunits.
receptors,
identified
through
anatomical
pharmacological
means,
underlie
tonic
inhibition
parvalbumin
(PV)
expressing
interneurons
(PV+INs)
critically
involved
generation
γ-oscillations.
When
orally
administered
twice
daily
2
wk,
restored
cognitive/memory
impairments
3-
4-mo-old
AD
mice
measured
by
their
performance
Barnes
maze.
Our
approach
is
unique
it
meant
enhance
memory
state-dependent
manner
engaging
amplifying
brain's
endogenous
enhancing
function
PV+INs.
