This is the first study to evaluate sensorimotor gating in patients with a diagnosis of IC/PBS. The results demonstrate that IC/PBS subjects as a group have a significant deficit in PPI compared to HCs, suggesting a decreased ability to adequately filter incoming information and perform appropriate sensorimotor gating. This deficit was seen at both the 60ms and 120 ms prepulse lead intervals. The PPI deficit was related to acute stress ratings during the experiment in the IC/PBS patients, with the greatest PPI decline seen in patients with increased stress reported during the study procedures. Although the prepulse paradigm is generally considered as not stress-inducing, patients reported significantly greater stress following the procedure than HCs. In contrast, increased neuroticism, in IC/PBS patients was associated with greater PPI.
Prior studies suggest that symptoms in IC/PBS may result in part from altered processing of interoceptive information, including augmented pain sensitivity and increased response to non-noxious sensations.5–7
IC/PBS patients demonstrate a deficit in the ability to habituate to non-noxious electrical and thermal stimulation to the T12 and S3 dermatomes.5, 6
In addition, IC/PBS patients demonstrate generalized hypersensitivity to deep tissue stimulation7
and pain during intravesical instillation of ice water.23
The current results indicate that a possible mechanism contributing to altered interoceptive information processing in IC/PBS may be the presence of a general deficit in filtering mechanisms for intero- and exteroceptive stimuli due to altered pre-attentive processing. While this alteration is evident in the IC/PBS subjects as a group and is greater in those patients with increased subjective ratings of the experimental situation as stressful, it appears that neuroticism had a significant moderating effect on the lowered PPI. Swerdlow et al24
reported increased PPI to be associated with higher scores on a psychological scale of illness fears and concerns (the Hysteria scale of the MMPI) in healthy subjects. Also, previous studies have shown that increased PPI may be associated with increased vigilance. PPI is greater when task demands require attention to the prepulse and less when instructions are to ignore the prepulse10
and is enhanced by threat conditions, presumably due to increased vigilance.25
IC/PBS patients score higher on the Kohn Reactivity Scale suggesting increased vigilance to a variety of stimuli.7
In the current data, IC/PBS subjects with greater neuroticism, a measure of trait anxiety associated with vigilance26
, showed greater PPI. Therefore, the data support a model in which the overall deficit in PPI associated with IC/PBS is less pronounced in subjects who are high in neuroticism and likely high in vigilance to relatively innocuous environmental cues like the prepulse.
While the brain structures mediating sensorimotor gating are in the pons, areas of the frontal cortex, in particular the anterior cingulate and lateral prefrontal cortex (PFC) provide `top down' influence via the thalamus.10
Lateral PFC also responds to experimental changes in bladder sensation and may play a crucial role in controlling the desire to void.27
Lateral PFC is involved in attentional processes and corticolimbic inhibition and has been implicated in endogenous pain inhibition. Alterations in corticolimbic-pontine interactions may therefore play a role in altered intero- and exteroceptive information processing, including visceral hyperalgesia in female IC/PBS patients. Additionally, medial PFC activity has been negatively associated with both neuroticism28
and attention modulated prepulse inhibition29
and may be involved in increased vigilance to the prepulse. We have previously shown in this same sample of IC/PBS patients an increase in startle during anticipation of an abdominal threat suggesting an increased sensitivity of the extended amygdala to some forms of stress.14
Further research that specifically examines processing of both exteroceptive and interoceptive stimuli is needed to clarify what may be overlapping brain mechanisms involved in increased pain sensitivity, increased trait anxiety and alterations in attention and information processing that are involved in vulnerability to develop and maintain IC/PBS symptoms.
Procedural differences that affect the signal to noise ratio of the prepulse, such as the presence or absence of a constant background sound can influence both the amount of PPI and group differences in PPI30
. Although the current methods led to robust levels of PPI, it will be important to test the consistency of these results using other PPI parameters and signal to noise ratios.
Although preliminary, this study suggests that IC/PBS is associated with deficits in early stage information processing and, specifically, inefficient gating of incoming sensory information. While altered sensorimotor gating may reflect a longstanding or even genetically based neurocognitive vulnerability factor for development of IC/PBS, it could also be a result of chronically altered interoceptive signals from the bladder. In any case, improper inhibition of responses to low level interoceptive stimulation may be a significant factor in long term symptom maintenance. Given previous studies that have shown vigilance can increase PPI, IC/PBS subjects with greater neuroticism/trait anxiety may have increased vigilance to environmental events, apparently mitigating a deficit in PPI. Further study is needed to examine the dynamics of the relationship between symptoms and altered information processing in IC/PBS patients.