Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI)
have increased at an astounding pace as the value of this neurobiologically informative
measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse)
is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the
magnitude of the startle response. In humans, PPI occurs in a robust, predictable
manner when the prepulse and startling stimuli occur in either the same or different
modalities (acoustic, visual, or cutaneous).
This review covers three areas of interest in human PPI studies. First, we review
the normal influences on PPI related to the underlying construct of sensori- (prepulse)
motor (startle reflex) gating. Second, we review PPI studies in psychopathological
disorders that form a family of gating disorders. Third, we review the relatively
limited but interesting and rapidly expanding literature on pharmacological influences
on PPI in humans.
All studies identified by a computerized literature search that addressed the three
topics of this review were compiled and evaluated. The principal studies were summarized
in appropriate tables.
The major influences on PPI as a measure of sensorimotor gating can be grouped into
11 domains. Most of these domains are similar across species, supporting the value
of PPI studies in translational comparisons across species. The most prominent literature
describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum
patients and their clinically unaffected relatives. These findings support the use
of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically
disordered patients with neuropathology involving cortico-striato-pallido-pontine
circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding
PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's
syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps
posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been
examined for their effects on PPI in healthy human subjects. In some cases, the alterations
in PPI produced by these drugs in animals correspond to similar effects in humans.
Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some
human studies. With some other compounds, however, the effects seen in humans appear
to differ from those reported in animals. For example, the PPI-increasing effects
of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are
opposite to the PPI-disruptive effects of these compounds in rodents.
Considerable evidence supports a high degree of homology between measures of PPI in
rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor
gating. Multiple investigations of PPI using a variety of methods and parameters confirm
that deficits in PPI are evident in schizophrenia-spectrum patients and in certain
other disorders in which gating mechanisms are disturbed. In contrast to the extensive
literature on clinical populations, much more work is required to clarify the degree
of correspondence between pharmacological effects on PPI in healthy humans and those
reported in animals.