Expectation of Pain Enhances Responses to Nonpainful Somatosensory Stimulation in the Anterior Cingulate Cortex and Parietal Operculum/Posterior Insula: an Event-Related Functional Magnetic Resonance Imaging Study

Abstract

Although behavioral studies suggest that pain distress may alter the perception of somatic stimulation, neural correlates underlying such alteration remain to be clarified. The present study was aimed to test the hypothesis that expectation of pain might amplify brain responses to somatosensory stimulation in the anterior cingulate cortex (ACC) and the region including parietal operculum and posterior insula (PO/PI), both of which may play roles in regulating pain-dependent behavior. We compared brain responses with and subjective evaluation of physically identical nonpainful warm stimuli between two psychologically different contexts: one linked with pain expectation by presenting the nonpainful stimuli randomly intermixed with painful stimuli and the other without. By applying the event-related functional magnetic resonance imaging technique, brain responses to the stimuli were assessed with respect to signal changes and activated volume, setting regions of interest on activated clusters in ACC and bilateral PO/PI defined by painful stimuli. As a result, the uncertain expectation of painful stimulus enhanced transient brain responses to nonpainful stimulus in ACC and PO/PI. The enhanced responses were revealed as a higher intensity of signal change in ACC and larger volume of activated voxels in PO/PI. Behavioral measurements demonstrated that expectation of painful stimulus amplified perceived unpleasantness of innocuous stimulus. From these findings, it is suggested that ACC and PO/PI are involved in modulation of affective aspect of sensory perception by the uncertain expectation of painful stimulus.

Neural correlates of a ‘pessimistic’ attitude when anticipating events of unknown emotional valence

“…Generally, the influence of internal psychological attitudes on brain activity when facing new events has also been described in other studies: the expectation of pain enhanced responses to nonpainful sensory stimuli in the ACC, posterior insula, and parietal operculum (Sawamoto et al, 2000). Placebo induced an increase of activity in midbrain and prefrontal areas during anticipation of thermal pain .…”

“…Chua et al, 1999;Ploghaus et al, 1999;Sawamoto et al, 2000;Phelps et al, 2001;O'Doherty et al, 2002;Ueda et al, 2003;Wager et al, 2004;Simmons et al, 2004;Bermpohl et al, 2006, Nitschke et al, 2006, distinct brain regions comprising dorsolateral and inferior prefrontal cortex, orbitofrontal cortex, cingulate gyrus, insula, amygdala, thalamus, midbrain, and parieto-occipital areas were principal regions of interest involved in the expectation of emotional stimuli with unknown valence.…”

Differential involvement of the hippocampus, anterior cingulate cortex, and basolateral amygdala in memory for context and footshock

“…47), and administration of noxious stimuli alone, such as hind paw formalin injections or footshock, as well as during training, induces c-Fos expression and increased ATP hydrolysis in the ACC (48,49). Studies of both monkeys and humans have shown that the ACC is activated by nociceptive stimuli as well as by the anticipation of pain (50)(51)(52). Recent findings indicate that the ACC is composed of at least two functionally distinct regions.…”

Neurophysiologic Correlates of Side Effects in Normal Subjects Randomized to Venlafaxine or Placebo

“…Changes in prefrontal EEG theta have been linked to activity in the anterior cingulate cortex (ACC), an area that has been implicated in the expectation of pain (Sawamoto et al, 2000) and unpleasant emotional stimuli (Ueda et al, 2003), and has been shown to have prognostic value for determining clinical response to antidepressant medications. In normal subjects, theta activity recorded from prefrontal surface electrodes has been positively correlated with activity in the ACC as measured by magnetoencephalography (MEG; Asada et al, 1999;Ishii, 1999) and positron emission tomography (PET; Pizzagalli et al, 2003).…”