Connectome-based individualized prediction of loneliness.

Loneliness is an increasingly prevalent condition linking with enhanced morbidity and premature mortality. Despite recent proposal on medicalization of loneliness, so far no effort has been made to establish a model capable of predicting loneliness at the individual level. Here, we applied a machine learning approach to decode loneliness from whole-brain resting-state functional connectivity. The relationship between whole-brain RSFC and loneliness was examined in a linear predictive model. The results revealed that individual loneliness could be predicted by within- and between-network connectivity of prefrontal, limbic, and temporal systems, which are involved in cognitive control, emotional processing, and social perceptions and communications, respectively. Key nodes that contributed to the prediction model comprised regions previously implicated in loneliness, including the dorsolateral prefrontal cortex, lateral orbital frontal cortex, ventromedial prefrontal cortex, caudate, amygdala, and temporal regions. Our findings also demonstrated that both loneliness and associated neural substrates are modulated by levels of Neuroticism and Extraversion. The current data-driven approach provides the first evidence on the predictive brain features of loneliness based on organizations of intrinsic brain networks. Our work represents initial efforts in the direction of making individualized prediction of loneliness that could be useful for diagnosis, prognosis, and treatment.