Researchers Uncover New Pathways In the Brain

By: 
Gary Boas
February 23, 2016

In a recent study, a team of investigators mapped the neuronal pathways between regions of the brain involved in homeostasis. Shown here, for example, are the neuroanatomic trajectories of the human lateral forebrain bundle (LFB) and the superolateral medial forebrain bundle (slMFB), from the right lateral (A) and superior (B) perspectives. Both are involved in what the investigators call the central homeostatic network.

The Martinos Center’s Brian Edlow and colleagues have found evidence of previously unidentified connections between regions of the brain. The findings, reported in the journal Brain Connectivity, could help to advance care for patients at risk for a range of homeostatic disorders.

In the Brain Connectivity study, the researchers mapped the neuronal pathways between regions of the brain known to play a role in homeostasis—in addition to mediating adaptations to stress, these pathways are implicated in diseases such as epilepsy and sudden infant death syndrome (SIDS).

They achieved this, said Edlow, Director of the MGH Laboratory for NeuroImaging of Coma and Consciousness and an affiliated faculty member in the MGH Martinos Center for Biomedical Imaging, by performing diffusion spectrum imaging tractography in six healthy subjects using the Human Connectome MRI scanner at the Center. The only one of its kind in the world at the time of the study, the scanner offers the angular resolution needed to disentangle the complex crossing neuronal fibers in the brain, particularly within the human brainstem.

The findings provided the initial evidence in the human brain for connectivity between homeostatic sites in the caudal brainstem and the forebrain, and furthermore supported the idea that these interconnected nodes form what the researchers call an integrated central homeostatic network (CHN). Better understandings of CHN connectivity in healthy subjects ultimately could facilitate improved care for patients with abnormal connectivity.

Edlow emphasized that the findings still need to be validated using other tract-tracing techniques in postmortem human brain tissue. If they are, though, they could provide a number of opportunities to improve care for patients with homeostatic disorders. For example, by mapping the potentially abnormal connections between the hippocampus and the brainstem in patients with temporal lobe epilepsy, clinicians may be able to identify patients at risk of Sudden Unexplained Death in Epilepsy (SUDEP) and even come up with personalized treatments to help prevent sudden death.

Another potential application: preventing Sudden Infant Death Syndrome. The laboratory of Hannah C. Kinney, a Boston Children’s Hospital researcher and the senior author of the Brain Connectivity study, has shown that there may be structural abnormalities in the hippocampus associated with increased risk of sudden death. “If we can identify these types of abnormalities in the nodes and/or connections of the CHN soon after birth,” Edlow said, “we can potentially develop new therapeutic strategies to prevent SIDS.”

The study also included co-first author Jennifer McNab and collaborating author Thomas Witzel, both of the Martinos Center, who performed acquisition, processing and analysis of the data.