Mid Sweden University

Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.

Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h²) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h² = 0.34) and autonomic responses (h² = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h² = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.