Loneliness is perceived as social isolation and exclusion. The neural substrate of loneliness has been investigated with functional neuroimaging; however, lesion-based studies and their associated outcomes are needed to infer causal involvement between brain regions and function. Here, we applied voxel-based lesion-symptom mapping (VLSM) analyses to investigate the causal role of brain lesions on self-report of loneliness (UCLA Loneliness Scale) in a unique sample from the Vietnam Head Injury Study, including veterans with penetrating traumatic brain injuries (pTBI) (n = 132) and healthy controls (HCs) (n = 35). Our results revealed that the right anterior insula (AI) and right prefrontal cortex (PFC) are key brain regions underpinning loneliness perception. Individuals with selective lesions to the right AI and right PFC were less likely to report loneliness compared to patients with selective lesions to the posterior cortex and HCs. Therefore, it appears that lesions to key regions involved in processing social pain act to lower the perception of loneliness. Reporting loneliness was associated with executive dysfunction, apathy, disinhibition, and lower life satisfaction. In conclusion, the reported findings broaden our understanding of how loneliness is processed in the social brain, and how behavioral and cognitive factors can influence this perception.

孤独感被视为社会孤立和排斥。已经通过功能性神经成像研究了孤独感的神经基础。然而，需要基于病变的研究及其相关结果来推断脑区域与功能之间的因果关系。在这里，我们应用了基于体素的病变症状图谱（VLSM）分析，以调查越南头部伤害研究的一个独特样本中，脑部病变对孤独症自我报告（UCLA孤独感量表）的因果作用，其中包括具有穿透性创伤的退伍军人脑损伤（pTBI）（n = 132）和健康对照（HCs）（n = 35）。我们的研究结果表明，右前岛（AI）和右前额叶皮层（PFC）是支撑孤独感的关键大脑区域。与对后皮质和HCs有选择性损害的患者相比，对AI和PFC具有选择性损害的患者报告孤独感的可能性较小。因此，似乎在涉及处理社会痛苦的关键区域的损害起到了降低孤独感的作用。报告孤独感与执行功能障碍，冷漠，禁忌和生活满意度降低有关。总之，所报告的发现扩大了我们对社交大脑中孤独感的处理方式以及行为和认知因素如何影响这种认知的理解。报告孤独感与执行功能障碍，冷漠，禁忌和生活满意度降低有关。总之，所报道的发现拓宽了我们对社交大脑中孤独感的处理方式以及行为和认知因素如何影响这种认知的理解。报告孤独感与执行功能障碍，冷漠，禁忌和生活满意度降低有关。总之，所报道的发现拓宽了我们对社交大脑中孤独感的处理方式以及行为和认知因素如何影响这种认知的理解。