Anterior cingulate cortex (ACC)
In a recent human neuroimaging study, scientists found that the dorsal portion of the ACC - an area specifically involved in the pain response - activated during social isolation (1).
Prefrontal cortex (PFC)
Isolated animals have deficits in learning associated with decreased functioning in the PFC (2). Scientists found that PFC neurons in isolated animals had fewer dendritic spines, structures that are essential for neuronal communication. When compared to non-isolated people, isolated humans show weaker neuronal activation in the PFC when they perform attentional tasks (2).
This brain area is part of the reward system, a neuronal circuit that produces feelings of pleasure. Viewing happy scenes of people typically activates the ventral striatum. However, when lonely people view these scenes, their ventral striatum response is hampered, leaving them to feel less pleasure from social stimulation (3).
Individuals who have been isolated for extended periods have shrunken himocampi and reduced blood-derived neurotrophic factor (BDNF), a protein that is important for long-term memory (8). These changes impair stress regulation, learning, and memory, causing poor performance on tests of spatial awareness and attention.
Lonely individuals tend to have smaller amygdalae, which plays a role in memory, decision making, and most importantly, emotional processing (6). When scientists studied isolated rats during development, they found distinct chemical and structural changes in the amygdala compared to socially active rats (7).
Loneliness associates with increased activity in the hypothalmic-pituitary-adrenal (HPA) axis, a major neuroendocrine system that regulates the body's response to stress (4). Isolation also increases the inflammatory response, leading to a higher risk of inflammatory disease (5).
- Eisenberger, N. I., Lieberman, M. D. & Williams, K. D. Does rejection hurt? An fMRI study of social exclusion. Science 302, 290-292 (2003).
- Cacioppo, J. T. & Hawkley, L. C. Perceived social isolation and cognition. Trends in Cognitive Sciences 13, 447-454 (2009).
- Cacioppo, J. T., Norris, C. J., Decety, J., Monteleone, G. & Nusbaum, H. In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. J Cogn Neurosci 21, 83-92 (2009).
- Cacioppo, J. T., Hawkley, L. C., Norman, G. J. & Berntson, G. G. Social isolation. Ann N Y Acad Sci 1231, 17-22 (2011).
- Cole, S. W. et al. Social regulation of gene expression in human leukocytes. Genome Biol 8, R189 (2007).
- Düzel, S. et al. Structural Brain Correlates of Loneliness among Older Adults. Scientific Reports 9, 13569 (2019).
- Lapiz, M. et al. Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission. Neurosci Behav Physiol 33, 13-29 (2003).
- Stahn, A. C. et al. Brain Changes in Response to Long Antarctic Expeditions. New Engl J Med 381, 2273-2275 (2019).