In the first resting state fMRI functional connectivity (FC) study on PSI,[7] PSI was found to be associated with increased resting-state FC between several nodes of the cingulo-opercular network, a neural network associated with tonic alertness. PSI was also associated with reduced resting-state FC between the cingulo-opercular network and the right superior frontal gyrus, suggesting diminished executive control. Cacioppo and colleagues (2009)[4] found that lonely individuals express weaker activation of the ventral striatum in response to pleasant pictures of people than of objects, suggesting decreased reward to social stimuli. Lonely individuals also expressed greater activation of the visual cortex in response to unpleasant depictions of people (i.e., negative facial expressions) than of objects; non-lonely individuals show greater activation of the right and left temporoparietal junction (TPJ), a region implicated in theory of mind. The authors interpreted the findings to represent that lonely individuals pay greater attention to negative social stimuli, but non-lonely individuals, to a greater degree than lonely individuals, insert themselves into the perspective of others. Moreover, Kanai et al. (2012) reported that loneliness negatively correlated with gray matter density in the left posterior temporal sulcus, an area involved in biological motion perception, mentalizing, and social perception.[8]
Overall, several neuroimaging studies in humans on perceived social isolation have emphasized implications of the visual cortex and right-hemispheric stress-related circuits underlying difference between lonely and non-lonely individuals. A recent[when?] population-genetics study marked a 50× increase in the neuroimaging research on perceived social isolation. The investigators tested for signatures of loneliness in grey matter morphology, intrinsic functional coupling, and fiber tract microstructure. The loneliness-linked neurobiological profiles converged on a collection of brain regions known as the default mode network. This higher associative network shows more consistent loneliness associations in grey matter volume than other cortical brain networks. Lonely individuals display stronger functional communication in the default network, and greater microstructural integrity of its fornix pathway. The findings fit with the possibility that the up-regulation of these neural circuits supports mentalizing, reminiscence and imagination to fill the social void.[9]