Nearly three years into the pandemic, the world is just regaining a sense of normalcy. While people once more socially interact in person, researchers are beginning to understand the biological effects of social isolation.
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SOCIABLE CIRCUITS
A neural circuit responsible for the social reward response unravels the mystery of what drives human sociality.
Interviewed by Angela Zhang, PhD
In human society, relationships are both rewarding and essential to everyday life, yet how the brain makes connections that establish relationships remains a mystery. Weizhe Hong, a neuroscientist at the University of California, Los Angeles, studies how the brain regulates social behavior from molecules to circuits.
Hong’s recent paper in Nature Neuroscience describes a newly discovered neural circuit underlying social reward in mice. This circuit positively reinforces social interactions and when activated, can even overcome behavior associated with negative experiences, making it crucial for future studies of social impairments in neurodevelopmental and neuropsychiatric disorders. As part of his research, he created an image of the mouse brain that captured the social reward circuit under the microscope.
What does this image show?
We study how animals find social interactions rewarding, and we try to identify neural circuits that mediate the social reward process. For this study, we focused on the medial amygdala, which detects social sensory cues. In the image, the blue is a counter stain for nuclei so that we can gain an idea of the overall brain structure, and the green depicts axonal projections from the GABAergic neurons of the medial amygdala to a hypothalamic area called the medial preoptic nucleus. We discovered that this pathway mediates the effects of social rewards.
How did you create the image?
We created a task where an animal made one of two choices. One option gave access to another animal to interact with for a few seconds, and the other option did nothing. Over days, the animal learned the choice that rewarded it with social interaction and developed a strong preference for that choice.
To study neural circuits in the brain that regulate social reward behavior, we used a modified experimental setup by replacing social interaction with stimulation of the social reward circuit shown in the image. Animals developed a preference for the choice that stimulated the same axons activated during social interaction, indicating that stimulating these axons was particularly rewarding to the animals. We visualized this social reward circuit under a microscope, and that is what we see in this image.
What is the next unanswered question you plan to address?
There are many questions. For example, how does this social reward circuit change in disease conditions such as autism spectrum disorder? Patients with autism have reduced or impaired social behavior. Could that be due to reduced social motivation and social reward? I believe that we can make unique contributions to this area by studying these circuits and using this experimental setup.
What implications does this study have for future research?
Normally, humans find a lot of things rewarding, like our favorite foods. The reason we like those foods is that they give us pleasant experiences. How is that different from the rewarding experience of social interaction? In this study, we identified unique brain areas dedicated to social interaction, and we found that this circuit activated by social interaction is not relevant to food rewards. I think that has profound implications for the study of motivation. Depression can decrease social reward and motivation, while addiction can hijack normal reward and motivation circuitry in the brain. This study improves understanding of what brain areas should be studied to understand altered social motivation.
This interview has been condensed and edited for clarity.
SOCIAL INTERACTION: A BASIC HUMAN NEED
Healthy relationships are vital for well-being.
By Sunitha Chari, PhD
In a world still grappling with a global pandemic after two years, social connections are not what they used to be. Mask mandates, social distancing, and virtual meetings have left many with feelings of social isolation. Loneliness is on the rise, especially among young adults. This “loneliness epidemic” increases the vulnerability of individuals to a plethora of mental and physical ailments, including depression, anxiety, and cardiovascular disorders (1).
Human well-being relies on intimate social connections. In a recent study published in Nature Neuroscience, a team of researchers led by Rebecca Saxe, a neuroscientist at the Massachusetts Institute of Technology, reported that social interaction is a basic human need, just like food and water (2).
In their study, Saxe and her team subjected 40 healthy volunteers to 10 hours of either fasting or social isolation. After the mandated fasting or isolation period, the volunteers reported craving food and social contact, respectively. Using functional MRI, the scientists found that the midbrain, particularly the area associated with reward processing, became activated during these cravings.
The anticipation of reward or punishment is a powerful modifier of behavior and drives humans to engage in activities with positive outcomes and avoid activities with negative outcomes (3). Positive social interactions serve as reward signals that activate reward processing circuits in the brain in the substantia nigra pars compacta and the ventral tegmental area (SN/VTA) (2, 4). Neurons in these regions release dopamine to stimulate feelings of pleasure (6).
People experience dopamine release positively and it provides an impetus to fulfill an unmet need.
Participants in the study experienced the lack of intimate connections, as a feeling of loneliness, which provoked them to seek social contact (2). However, other studies have implicated chronic loneliness in structural changes to the midbrain that correspond with a decreased dopamine response. These structural changes correlated with behavioral changes that led people to become inhibited, fearful, and less trusting of others, while simultaneously making them self-centered and avoidant (6).
The findings from these studies highlight the importance of intimate social connections for a healthy brain and mental well-being. Digital technologies played a crucial role during the pandemic by virtually connecting individuals with their loved ones. Now, scientists are exploring whether or not digital social interactions stimulate the same reward circuits in the brain as physical interactions. Physical isolation sparked by the pandemic and the increasing loneliness epidemic suggest that physical social interaction may be simply irreplaceable.
REFERENCES
1. Weissbourd, R., Batanova, M., Lovison, V., Torres, E. Loneliness in America. How the pandemic has deepened an epidemic of loneliness and what we can do about it. Harvard Graduate School of Education. Making Caring Common Project https://mcc.gse.harvard.edu/reports/loneliness-in-america (2020).
2. Tomova, L., et al. Acute social isolation evokes midbrain craving responses similar to hunger. Nat Neurosci. 23(12), 1597-1605 (2020).
3. Clark, A. M. Reward processing: a global brain phenomenon? J Neurophysiol. 109(1), 1-4 (2013).
4. Izuma, K., Saito, D. N., & Sadato, N. Processing of social and monetary rewards in the human striatum. Neuron. 58(2), 284-294 (2008).
5. Bressan, R. A., Crippa, J. A. The role of dopamine in reward and pleasure behaviour—review of data from preclinical research. Acta Psychiatr Scand Suppl. 111(427), 14-21 (2005)
6. Cacioppo, J. T., et al. In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. Journal of Cognitive Neuroscience. 21(1), 83–92 (2009)
How Social Isolation Affects the Brain
During the pandemic, many individuals selected a handful of friends and family with whom to form social bubbles. This drastic reduction in daily social interactions led to increased cases of mental health distress, demonstrating how social isolation alters brain patterns.
By Angela Zhang, PhD
Designed by Janette Lee-Latour
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 exclusion (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).
Ventral striatum
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).
Hippocampus
Individuals who have been socially isolated for extended periods have shrunken hippocampi 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.
Amygdala
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).
Hypothalamus
Loneliness associates with increased activity in the hypothalamic-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).
References
1. Eisenberger, N. I., Lieberman, M. D. & Williams, K. D. Does rejection hurt? An fMRI study of social exclusion. Science 302, 290-292 (2003).
2. Cacioppo, J. T. & Hawkley, L. C. Perceived social isolation and cognition. Trends in Cognitive Sciences 13, 447-454 (2009).
3. 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).
4. Cacioppo, J. T., Hawkley, L. C., Norman, G. J. & Berntson, G. G. Social isolation. Ann. N. Y. Acad. Sci. 1231, 17-22 (2011).
5. Cole, S. W. et al. Social regulation of gene expression in human leukocytes. Genome Biol 8, R189 (2007).
6. Düzel, S. et al. Structural Brain Correlates of Loneliness among Older Adults. Scientific Reports 9, 13569 (2019).
7. 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).
8. Stahn, A. C. et al. Brain Changes in Response to Long Antarctic Expeditions. New Engl. J. Med. 381, 2273-2275 (2019).