Monoaminergic modulation of emotional impact in the inferomedial prefrontal cortex

Abstract

People assess the impact of emotionally loaded images differently. We define this impact as the average difference between individual ratings of standardized ''pleasant'' and ''unpleasant'' images. To determine the neuroanatomical correlate of a hypothetical interaction between emotional impact and cerebral excitability, we first determined the individual effect on cerebral blood flow of a pharmacological challenge with the monoamine reuptake inhibitor clomipramine in nine healthy volunteers. In a later, independent, session the nine volunteers rated pleasant, neutral, and unpleasant images of the standard Empathy Picture System on a scale from 13 to 23. We then used regression analysis to identify sites in the ventromedial prefrontal cortex at which the two separately acquired measures, blood flow change and emotional impact of images, correlated significantly. The regression analysis identified a locus in Brodmann's area 11 of the inferomedial prefrontal cortex (IMPC) at which these two separate measures had significant inverse correlation. Thus, under the specific circumstance of positron emission tomography (PET) of a pharmacological challenge, a key region of the inferomedial prefrontal cortex underwent deactivation in proportion to a separately rated emotional impact of a stimulus. We propose a specific pharmacodynamic mechanism that explains the correlation between the emotional impact and the effect of a serotonin-noradrenaline reuptake inhibitor on cerebral blood flow.

Deep Brain Stimulation Reveals Emotional Impact Processing in Ventromedial Prefrontal Cortex

“…In this previous study (File S1), the change of activity in each subject correlated inversely with the emotional impact of standardized emotive images presented to the subjects in separate sessions [1]. In that study, we proposed that the inverse relation is linked to differential distributions of inhibitory and excitatory monoamine receptors in this region.…”

“…Details of the PET measurements of cerebral blood flow with oxygen-15-labeled water were given by Geday et al [5], [6] and Geday and Gjedde [1]. We analyzed the PET images of blood flow on and off the DBS and determined the changes of blood flow elicited by the DBS in a 6 mm radius sphere centred on the Talairach coordinates (1, 55, −13, x,y,z mm), identified as the site of the previously reported interaction between serotonergic-noradrenergic tone and emotional impact [1].…”

“…We analyzed the PET images of blood flow on and off the DBS and determined the changes of blood flow elicited by the DBS in a 6 mm radius sphere centred on the Talairach coordinates (1, 55, −13, x,y,z mm), identified as the site of the previously reported interaction between serotonergic-noradrenergic tone and emotional impact [1]. During the PET measurements, the subjects passively viewed the images of the standardized Empathy Picture System (EPS) [7], as described by Geday et al [5].…”

“…We recorded the emotional impact of the images in a separate session with the DBS stimulation off and on, respectively. As in the study reported by Geday and Gjedde [1], we defined the impact as the numerical difference between ratings of unpleasant and pleasant images included in the standardized Empathy Picture System in the separate session with the subjects off and on the DBS.…”

“…In addition to the global analysis of all cortical gray matter (excluding the cerebellum), we restricted a search to a volume of interest (VOI) consisting of one 6-mm-radius sphere centered on a site in the right inferior medial prefrontal cortex (IMPC) previously shown to be deactivated by emotional content [1], [5]–[7] at the Talairach coordinates (x, y, z mm) 1, 55, −13. Threshold t-statistics of the restricted search was 3.46 for P<0.05 with 46 degrees of freedom with a search volume of 0.984 cm 3 at an FWHM of 12 mm.…”