Motor, cognitive, and affective areas of the cerebral cortex influence the adrenal medulla

Significance How does the “mind” (brain) influence the “body” (internal organs)? We identified key areas in the primate cerebral cortex that are linked through multisynaptic connections to the adrenal medulla. The most substantial influence originates from a broad network of motor areas that are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. A smaller influence originates from a network in medial prefrontal cortex that is involved in the regulation of cognition and emotion. Thus, cortical areas involved in the control of movement, cognition, and affect are potential sources of central commands to influence sympathetic arousal. These results provide an anatomical basis for psychosomatic illness where mental states can alter organ function. Modern medicine has generally viewed the concept of “psychosomatic” disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.