Introduction: Anterior cingulate cortex (ACC) is one of the cortical receptive fields of afferent nerves innervating the visceral organs and modulates autonomic nervous system in collaboration with hypothalamus and brainstem. Cardiac afferent nerves are associated with not only chest pain but also sympathetic arousal in heart failure, in which ACC could be involved. However, the cortical receptive fields of cardiac afferent nerves still remain to be elucidated. Hypothesis: We thus investigated whether ACC is activated in response to cardiac electrical stimulation in humans. Methods: We studied 10 patients (74.7±1.9 yrs, M/F 9/1) with cardiac pacemaker implantation. Before the measurement, mode of cardiac pacemaker was changed to VVI 80-90 bpm with 1.5V intensity. Cerebral blood flow (CBF) was measured using [15O]H2O positron emission tomography (PET) during sham stimulation (1.5V) and intense stimulation (7.5-8V). The CBF images of intense stimulation were compared with those of sham stimulation using SPM8, a common analysis tool for neuroimages. Cardiac sensation was evaluated with an ordinate scale after CBF measurements. Blood samples were obtained from the cubital vein before and after CBF measurements for plasma catecholamine levels (one patient was excluded for the analysis due to urination before the last blood sampling). Results: Intense stimulation did not induce cardiac sensation but significantly increased plasma adrenaline levels as compared with sham stimulation (intense, 6.1±1.8 vs. sham, 0.1±3.0 pg/ml, P=0.031, n=9 each). CBF in ACC was significantly increased in response to intense stimulation as compared with sham stimulation (intense, 64.6±0.7 vs. sham, 61.0±1.3 ml/100g/min, P=0.008, n=10 each) ( Figure, yellow arrowhead ). Conclusions: This study demonstrates for the first time that ACC could be the cortical receptive field of cardiac afferent nerves associated with sympathetic arousal in humans.