The Annual Review of Pharmacology and Toxicology,
Journal Year:
2023,
Volume and Issue:
64(1), P. 313 - 338
Published: Aug. 16, 2023
Apathy
is
a
disabling
syndrome
associated
with
poor
functional
outcomes
that
common
across
broad
range
of
neurological
and
psychiatric
conditions.
Currently,
there
are
no
established
therapies
specifically
for
the
condition,
safe
effective
treatments
urgently
needed.
Advances
in
understanding
motivation
goal-directed
behavior
humans
animals
have
shed
light
on
cognitive
neurobiological
mechanisms
contributing
to
apathy,
providing
an
important
foundation
development
new
treatments.
Here,
we
review
components,
neural
circuitry,
pharmacology
apathy
motivation,
highlighting
converging
evidence
shared
transdiagnostic
mechanisms.
Though
pharmacological
yet
been
licensed,
summarize
trials
existing
novel
compounds
date,
identifying
several
promising
candidates
clinical
use
avenues
future
drug
development.
Science,
Journal Year:
2022,
Volume and Issue:
378(6626)
Published: Dec. 8, 2022
Learning
to
predict
rewards
based
on
environmental
cues
is
essential
for
survival.
It
believed
that
animals
learn
by
updating
predictions
whenever
the
outcome
deviates
from
expectations,
and
such
reward
prediction
errors
(RPEs)
are
signaled
mesolimbic
dopamine
system-a
key
controller
of
learning.
However,
instead
learning
prospective
RPEs,
can
infer
retrospective
cause
rewards.
Hence,
whether
conveys
a
causal
associative
signal
sometimes
resembles
RPE
remains
unknown.
We
developed
an
algorithm
found
release
associations
but
not
RPE,
thereby
challenging
dominant
theory
Our
results
reshape
conceptual
biological
framework
Annual Review of Neuroscience,
Journal Year:
2023,
Volume and Issue:
46(1), P. 359 - 380
Published: April 18, 2023
Striosomes
form
neurochemically
specialized
compartments
of
the
striatum
embedded
in
a
large
matrix
made
up
modules
called
matrisomes.
Striosome-matrix
architecture
is
multiplexed
with
canonical
direct-indirect
organization
striatum.
Striosomal
functions
remain
to
be
fully
clarified,
but
key
information
emerging.
First,
striosomes
powerfully
innervate
nigral
dopamine-containing
neurons
and
can
completely
shut
down
their
activity,
following
rebound
excitation.
Second,
receive
limbic
cognition-related
corticostriatal
afferents
are
dynamically
modulated
relation
value-based
actions.
Third,
spatially
interspersed
among
matrisomes
interneurons
influenced
by
local
global
neuromodulatory
oscillatory
activities.
Fourth,
tune
engagement
motivation
perform
reinforcement
learning,
manifest
stereotypical
behaviors,
navigate
valence
conflicts
discriminations.
We
suggest
that,
at
an
algorithmic
level,
could
serve
as
distributed
scaffolds
provide
formats
striatal
computations
generated
through
development
refined
learning.
propose
that
affect
subjective
states.
By
transforming
corticothalamic
other
inputs
functional
striatum,
they
implement
state
transitions
nigro-striato-nigral
circuits
bodily
cognitive
actions
according
internal
motives
whose
compromised
neuropsychiatric
conditions.
Neuron,
Journal Year:
2023,
Volume and Issue:
111(21), P. 3465 - 3478.e7
Published: Aug. 22, 2023
Animals
frequently
make
decisions
based
on
expectations
of
future
reward
("values").
Values
are
updated
by
ongoing
experience:
places
and
choices
that
result
in
assigned
greater
value.
Yet,
the
specific
algorithms
used
brain
for
such
credit
assignment
remain
unclear.
We
monitored
accumbens
dopamine
as
rats
foraged
rewards
a
complex,
changing
environment.
observed
brief
pulses
both
at
receipt
(scaling
with
prediction
error)
novel
path
opportunities.
Dopamine
also
ramped
up
ran
toward
ports,
proportion
to
value
each
location.
By
examining
evolution
these
place-value
signals,
we
found
evidence
two
distinct
update
processes:
progressive
propagation
along
taken
paths,
temporal
difference
learning,
inference
throughout
maze,
using
internal
models.
Our
results
demonstrate
within
rich,
naturalistic
environments
conveys
place
values
via
multiple,
complementary
learning
algorithms.
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(22)
Published: May 29, 2024
Learning
causal
relationships
relies
on
understanding
how
often
one
event
precedes
another.
To
investigate
dopamine
neuron
activity
and
neurotransmitter
release
change
when
a
retrospective
relationship
is
degraded
for
specific
pair
of
events,
we
used
outcome-selective
Pavlovian
contingency
degradation
in
rats.
Conditioned
responding
was
attenuated
the
cue-reward
that
degraded,
as
midbrain
ventral
striatum
response
to
cue
subsequent
reward.
Contingency
also
abolished
trial-by-trial
history
dependence
responses
at
time
trial
outcome.
This
profile
changes
cue-
reward-evoked
not
easily
explained
by
standard
reinforcement
learning
model.
An
alternative
model
based
better
able
capture
during
degradation,
well
conditioned
behavior
following
optogenetic
manipulations
noncontingent
rewards.
Our
results
suggest
mesostriatal
encodes
contingencies
between
meaningful
events
learning.
Cognitive Affective & Behavioral Neuroscience,
Journal Year:
2024,
Volume and Issue:
24(2), P. 228 - 245
Published: Feb. 14, 2024
Abstract
Anxiety
disorders
affect
millions
of
people
worldwide
and
present
a
challenge
in
neuroscience
research
because
their
substantial
heterogeneity
clinical
presentation.
While
great
deal
progress
has
been
made
understanding
the
neurobiology
fear
anxiety,
these
insights
have
not
led
to
effective
treatments.
Understanding
relationship
between
phenotypic
underlying
biology
is
critical
first
step
solving
this
problem.
We
show
translation,
reverse
computational
modeling
can
contribute
refined,
cross-species
anxiety
as
well
disorders.
More
specifically,
we
outline
how
animal
models
be
leveraged
develop
testable
hypotheses
humans
by
using
targeted,
approaches
ethologically
informed
behavioral
paradigms.
discuss
translational
that
guide
prioritize
nontraditional
species.
Finally,
advocate
for
use
harmonize
cross-methodology
into
anxiety.
Together,
approach
will
help
bridge
widening
gap
currently
conceptualize
diagnose
disorders,
aid
discovery
better
treatments
conditions.
