Perceived social isolation, or loneliness, affects both physical and mental wellbeing, and this holiday season will be particularly lonely for many people as social distancing due to COVID-19 continues. A new study, headed by a team at McGill University, has now identified neurobiological signatures in the brains of lonely people that make them distinct in fundamental ways, based both on variations in the volume of different brain regions, as well as on how those regions communicate with one another across brain networks.

“We are just beginning to understand the impact of loneliness on the brain,” said Danilo Bzdok, PhD, a researcher at the Neuro (Montreal Neurological Institute-Hospital) and the Quebec Artificial Intelligence Institute. “Expanding our knowledge in this area will help us to better appreciate the urgency of reducing loneliness in today’s society.” Bzdok, together with research co-lead Nathan Spreng, PhD, and colleagues, published their findings in Nature Communications, in a paper titled, “The default network of the human brain is associated with perceived social isolation.”

Loneliness is estimated to affect 10–20% of adults who lack companionship, or consider themselves left out or isolated from others, the researchers commented. The health burden of loneliness is “pervasive,” and associated with morbidity, hypertension, and immune system dysfunction, as well as risk of suicide. Lonely people are typically more prone to major psychiatric disorders and cognitive decline, and have an increased risk of dementia. “A sense of loneliness has also been associated with health risks that are equivalent to or exceed that of obesity or smoking 15 cigarettes daily,” they wrote. However, the authors noted, “Despite severe consequences on behavior and health, the neural basis of loneliness remains elusive.”

Danilo Bzdok, PhD, is senior author on a paper showing a unique neural “signature” of loneliness. [The Neuro]

For their studies, the team focused on “time-enduring,” or “trait” loneliness. “This is distinct from the amount of time spent alone, or the frequency of social contact,” they explained. “While there is growing evidence that social connectedness may be associated with brain structure and function … in the current report we directly investigate the neural correlates linked to trait loneliness, that is, the negative subjective experience of social isolation.”

To do this, the researchers carried out a systematic assessment of how trait loneliness is manifested in the human brain. In fact, they wrote, research has already hinted at the existence of a “lonely brain.” The team examined the magnetic resonance imaging (MRI) data, genetics, and psychological self-assessments of approximately 40,000 middle-aged and older adults who volunteered to have their information included in the U.K. Biobank, an open-access database available to scientists around the world. The investigators then compared the MRI data of participants who reported often feeling lonely with the data from those who did not.

They found several differences in the brains of lonely people. These brain manifestations were centered on the “default network,” a set of brain regions involved in inner thoughts such as reminiscing, future planning, imagining, and thinking about others. “The default network is an assembly of higher association areas, which is known to overlap with the human social brain,” they explained. They found that the default networks of lonely people were more strongly wired together and, surprisingly, the grey matter volume in regions of the default network was greater in these individuals.

Nathan Spreng, PhD, is the study’s first author. [The Neuro]

Loneliness also correlated with differences in the fornix: a bundle of nerve fibers that carries signals from the hippocampus to the default network. In lonely people, the structure of this fiber tract was better preserved. “The loneliness-linked neurobiological profiles converge on a collection of brain regions known as the ‘default network’,” the scientists wrote. “Gray matter volumes, intrinsic functional connectivity, and white matter tract integrity showed distinctive features in the ‘lonely brain’ … Lonely individuals display stronger functional communication in the default network, and greater microstructural integrity of its fornix pathway.”

The default network is involved in functions such as how we remember the past, envision the future, or think about a hypothetical present. “The default network is well-known to be implicated in mental representations of oneself across time and space, including the reconstruction of one’s personal past, prospecting and planning about an envisioned future, imagination, and creative thought as well as simulating thoughts, places, and events,” the investigators commented. “The default network is also recognized for its role in representing other people, including their intentions, identity, and affiliation.”

The researchers suggest that the fact that the structure and function of this network are positively associated with loneliness may be because lonely people are more likely to use imagination, memories of the past, or hopes for the future to overcome their social isolation. “The findings fit with the possibility that the up-regulation of these neural circuits supports mentalizing, reminiscence, and imagination to fill the social void,” the team commented.

“In the absence of desired social experiences, lonely individuals may be biased towards internally-directed thoughts such as reminiscing or imagining social experiences. We know these cognitive abilities are mediated by the default network brain regions,” said Spreng from the Neuro of McGill University, who is first author on the paper. “So this heightened focus on self-reflection, and possibly imagined social experiences, would naturally engage the memory-based functions of the default network … As our core conclusion, brain divergence found in lonely, compared to non-lonely, individuals centered on the default network. We speculate that the associations between the default network and loneliness revealed here reflect increased demands on episodic mental simulation of inner social events in the absence of desired social experience in the external world.”

Loneliness is increasingly being recognized as a major health problem, and previous studies have shown older people who experience loneliness have a higher risk of cognitive decline and dementia. Understanding how loneliness manifests itself in the brain could be key to preventing neurological disease and developing better treatments, the team believes.

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