N EWS
problems such as addiction and
eating disorders.
Researchers led by neuroscien-
tist Shelly Flagel of the University
of Michigan have found a brain
circuit that may control this
hijacking; rats that exhibit a type
of compulsive behavior show
different brain connectivity and
activity than those that do not,
and manipulation of the circuit
altered their behavior. These
findings may help researchers
understand why some individuals
are more susceptible to im-
pulse-control disorders. “This
is technically a really excellent
study,” says neuroscientist Jeff
Dalley of the University of Cam-
bridge, who was not involved in
the work.
In the study, published last
September in eLife, researchers
showed rats an inert lever shortly
before delivering a tasty treat via
a chute, then sorted them into
groups based on their responses.
All rats learned to associate the
lever with the treat, but some—
dubbed “goal trackers”—began
to approach the food chute
directly after seeing the lever,
whereas inherent “sign trackers”
kept compulsively returning to
the lever itself.
The team suspected that two
brain regions were involved:
the paraventricular nucleus of
the thalamus (PVT), which drives
behavior, and the prelimbic
cortex, which is involved in re ward
learning. The researchers used
a technique called chemogenet-
ics to alter neurons in the circuit
connecting these regions, which
let them turn on or inhibit signals
from the prelimbic cortex using
drugs. Activating the circuit
reduced sign trackers' tendency
to approach the lever but did not
affect goal trackers. Deactivating
it drew goal trackers to the lever
(sign-tracking behavior), without
affecting preexisting sign track-
ers. The team also found in-
creased dopamine, a chemical
messenger involved in reward
processing, in the newly sign-
tracking brains.
The prelimbic cortex appears
to exert top-down control,
whereas the PVT processes
the motivational signal triggered
by the cue. “Individuals seem to
be wired differently regarding
this balance between top-downcortical control versus bottom-up
subcortical processes that are
more emotional,” Flagel says.
Those “who are highly reactive
to cues in the environment may
suffer from deficits in top-down
control.” She suggests that
cognitive-training therapies might
combat such deficits in humans.
The circuit itself could also
represent a new treatment target,
but the exact human anatomy
is unclear, Dalley notes—and
addiction is more complex than
a single mechanism.
Next, the researchers will try
to examine these traits in people.
“Once we’ve established the sign-
and goal-tracker paradigm in
humans, we can test whether
these traits are predictive of
psychopathology,” Flagel says.
“We hope this will help identify
individuals who are more suscep-
tible to certain mental illnesses
or facets such as relapse.”
—Simon Makin