The Structural Connectome of the Human Central Homeostatic Network

Abstract

Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

Variability of the medullary arcuate nucleus in humans

“…Furthermore, we want to evaluate the neuroanatomic connections of the AN, via interneuronal synapses, with other nerve centers with the aim to provide valuable insight on the variable behavior of the AN in human adults. Already, Edlow, McNab, Witzel, and Kinney (), using ultra‐high resolution diffusion spectrum imaging tractography, have recently demonstrated in healthy adults the presence of integrated central homeostatic networks (CHN) between autonomic and cardiorespiratory nuclei in the human brainstem and forebrain sites critical to homeostatic control. A “CHN connectome” has been defined in particular by these authors between the raphé nuclei in the brainstem and the medial temporal lobe.…”

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal

“…manually traced each TMB onto the Harvard AAN Atlas, version 1.0, which is a template of AAN nuclei in standard Montreal Neurological Institute (MNI152 1mm) space. This anatomic template, which is freely available online (www.martinos.org/resources/aan-atlas), is based upon histologic and ultra-high resolution MRI data from a human brainstem specimen [18] and has been used in recent studies of brainstem connectivity [30]. Axial images from the AAN atlas were selected for TMB tracing based upon visual identification of anatomic landmarks.…”

The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model

“…A recent study on human brains also revealed that the subiculum possesses extensive collaterals projected to the brainstem (59). It is well known that a monosynaptic pathway exists between the subiculum and PFC, the midline thalamus connects the two regions through a polysynaptic path (60).…”