Neuroimaging identifies previously unknown circuitry in brain homeostasis.


Homeostasis is the property of a system in which variables are regulated so that internal conditions remain stable and relatively constant.  The human body manages a multitude of highly complex variables to maintain balance or return systems to functioning within a normal range.  It is known that the liver, kidneys, and the brain help maintain this homeostasis. Deep within the human forebrain lies a group of structures that play major roles in autonomic, respiratory, neuroendocrine, emotional, immune, and cognitive adaptations to stress, known as the limbic system.

Studies show that 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.  Now, a study from researchers at Harvard Medical School, Massachusetts General Hospital, Boston Children’s Hospital and Stanford University identifies neuroanatomic connections between the brainstem regions involved in autonomic and cardiorespiratory function and forebrain regions involved in homeostatic control.  The team state that their findings provide evidence of previously unidentified structural connections between the human brainstem and forebrain.  The opensource study is published in the journal Brain Connectivity.

Previous studies show that homeostatic forebrain nodes receive sensory information concerning extrinsic threats and intrinsic metabolic derangements from the brainstem, resulting in arousal from sleep, heightened attention and vigilance during waking, and visceral and somatic motor defenses.  Yet despite emerging evidence for brainstem–forebrain interactions in regulating homeostasis, little direct information about the neuroanatomic connections between homeostatic regions of the brainstem and forebrain is available in the human brain. The current study provides an initial foundation for elucidating the connectome of homeostasis in the normal human brain, as well as for mapping disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

The current study utilised ultra-high resolution diffusion spectrum imaging tractography in the brains of six healthy human adults using the MGH-USC Connectome MRI scanner to elucidate the structural connectome of selected brainstem and forebrain regions related to homeostasis. Results provide evidence of a ‘central homeostatic network’ (CHN) that expands upon prior models of the limbic system by integrating forebrain and brainstem structures involved in human homeostasis.

Data findings identify specific connections between six brainstem sites and seven forebrain regions that play a role in the critical function of homeostasis. Results show that this is the process by which the brain integrates the regulatory and restorative systems in the body to maintain health and adapt to environmental challenges.  The lab state that their findings lay the foundation for further exploration of the neuroanatomic basis of homeostasis in the normal human brain. They go on to add that their data also provides a basis for studying the potential role that abnormal connectivity in this brain network may play in disorders of homeostasis, such as sudden death and epilepsy.

The team surmise that their study has detected previously unknown neural anatomy using the MGH-USC Human Connectome MRI scanner.  For the future, the researchers state that they envision that a connectogram can be built for each disorder of the CHN based upon cohort analysis, enabling clinicians to define which nodes and/or connections are pathogenic and warrant targeted therapies. They go on to conclude that it may be possible to use structural connectivity maps to pinpoint specific fiber bundles involved in different homeostatic disorders.

Source: Mary Ann Liebert, Inc./Genetic Engineering News

 

Divergence of the medial forebrain bundle, LFB, and ventral tegmental tracts in the posterior hypothalamus. (A) Anterior view of streamlines generated from the locus coeruleus (dark blue), dorsal raphe (turquoise), and median raphe (green) superimposed upon axial and coronal T1-weighted images (center inset) for a representative subject. In the posterior hypothalamus, streamlines from the locus coeruleus, dorsal raphe, and median raphe diverge as the follows: (1) slMFB, connecting to the prefrontal cortex; (2) VTTR, connecting to the paraventricular nuclei of the thalamus (Thal); (3) the VTTC, connecting to the anterior hypothalamus and basal forebrain, running alongside the imMFB; and (4) LFB, connecting to temporal limbic sites. (B) Zoomed view of the image in (A) demonstrates the divergence of the slMFB, VTTR, VTTC, and LFB in the posterior hypothalamus. Anatomic landmark; third ventricle (3V).  The Structural Connectome of the Human Central Homeostatic Network.  Edlow et al 2015.

Divergence of the medial forebrain bundle, LFB, and ventral tegmental tracts in the posterior hypothalamus. (A) Anterior view of streamlines generated from the locus coeruleus (dark blue), dorsal raphe (turquoise), and median raphe (green) superimposed upon axial and coronal T1-weighted images (center inset) for a representative subject. In the posterior hypothalamus, streamlines from the locus coeruleus, dorsal raphe, and median raphe diverge as the follows: (1) slMFB, connecting to the prefrontal cortex; (2) VTTR, connecting to the paraventricular nuclei of the thalamus (Thal); (3) the VTTC, connecting to the anterior hypothalamus and basal forebrain, running alongside the imMFB; and (4) LFB, connecting to temporal limbic sites. (B) Zoomed view of the image in (A) demonstrates the divergence of the slMFB, VTTR, VTTC, and LFB in the posterior hypothalamus. Anatomic landmark; third ventricle (3V). The Structural Connectome of the Human Central Homeostatic Network. Edlow et al 2015.

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