Peng Shaoling, Schaper Frederic L W V J, Cohen-Zimerman Shira, Miller Gillian N, Jiang Jing, Rouhl Rob P W, Temel Yasin, Siddiqi Shan H, Grafman Jordan, Fox Michael D, Cohen Alexander L
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Biol Psychiatry. 2025 Jun 15;97(12):1175-1185. doi: 10.1016/j.biopsych.2024.09.022. Epub 2024 Oct 4.
Aggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients. The neural mechanisms of aggression are unclear and treatment options are limited.
Using a recently validated lesion network mapping technique, we derived an aggression-associated network by analyzing data from 182 patients who had experienced penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression-related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 852). To explore potential therapeutic relevance of this network, we used an independent deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects.
We found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex. This network involves positive connectivity to the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 24 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression-associated network. Deep brain stimulation site connectivity to this same network was associated with increased irritability.
We conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.
攻击行为给人类社会造成了重大损失，在神经精神疾病患者中极为普遍。攻击行为的神经机制尚不清楚，治疗选择也有限。
我们使用一种最近经过验证的损伤网络映射技术，通过分析182名在越南战争服役期间遭受穿透性头部损伤的患者的数据，得出了一个与攻击行为相关的网络。为了测试该损伤衍生网络的损伤是否会增加与攻击行为相关的神经精神症状的风险，我们使用了哈佛损伤数据库（N = 852）。为了探索该网络的潜在治疗相关性，我们使用了一个由25名癫痫患者组成的独立深部脑刺激数据集，其中易怒和攻击行为是已知的潜在副作用。
我们发现与攻击行为相关的损伤发生在许多不同的脑区，但其特征是一个特定的脑网络，该网络通过与右侧前额叶皮质一个枢纽区域的功能连接来定义。这个网络包括与腹内侧前额叶皮质、背外侧前额叶皮质、额极、后扣带回皮质、前扣带回皮质、颞顶交界区和颞叶外侧的正性连接，以及与杏仁核、海马体、脑岛和视觉皮质的负性连接。在哈佛损伤数据库中包含的所有24种神经精神症状中，犯罪行为与我们的攻击行为相关网络最为匹配。深部脑刺激部位与同一网络的连接与易怒性增加有关。
我们得出结论，与攻击行为相关的脑损伤映射到一个特定的人类脑回路，该回路中功能连接的区域为治疗性神经调节提供了可测试的靶点。
