In the middle of the human brain there is a tiny struc­ture shaped like an elon­gated donut that plays a cru­cial role in man­aging how the body func­tions. Mea­suring just 10 mil­lime­ters in length and six mil­lime­ters in diam­eter, the hollow struc­ture is involved in a com­plex array of behav­ioral, cog­ni­tive, and affec­tive phe­nomena, such as the fight or flight response, pain reg­u­la­tion, and even sexual activity, according to North­eastern senior research sci­en­tist Ajay Satpute.

With a name longer than the struc­ture itself, the “mid­brain peri­aque­ductal gray region,” or PAG, is extra­or­di­narily dif­fi­cult to inves­ti­gate in humans because of its size and intri­cate struc­ture, he said.

In research pub­lished online this week in the journal Pro­ceed­ings of the National Academy of Sci­ence, Sat­pute and his col­leagues at Northeastern’s Inter­dis­ci­pli­nary Affec­tive Sci­ence Lab­o­ra­tory explain how they hur­dled these chal­lenges by using state-​​of-​​the art imaging to cap­ture this com­plex neural activity. The research could ulti­mately help sci­en­tists explore the grounds of human emo­tion like never before.

This fmri brain scan is related to the research.

Using a high-​​field strength fMRI magnet, Ajay Sat­pute and his colleagues in the Interdisciplinary Affective Science Lab achieved images of the human brain stem (left and center) at resolutions not possible before (right). Credited to Ajay Satpute, Northeastern University.

“The PAG’s func­tional prop­er­ties occur at such small spa­tial scales that we need to cap­ture its activity at very high res­o­lu­tion in order to under­stand it,” he explained.

Until recently, neu­roimaging studies have been car­ried out on func­tional mag­netic res­o­nance imaging, or fMRI, instru­ments con­taining mag­nets of up to three Teslas, a mea­sure of mag­netic field strength. These instru­ments pro­vide crit­ical data for under­standing how the brain’s dif­ferent areas respond to dif­ferent stimuli, but when those areas become suf­fi­ciently small and com­pli­cated, their res­o­lu­tion falls short.

In the case of the tiny PAG, this problem is para­mount because the PAG wraps around a hollow core, or “aque­duct,” con­taining cere­brospinal fluid, Sat­pute said. Tra­di­tional fMRI instru­ments cannot dis­tin­guish neural activity occur­ring in the PAG from that occur­ring in the CS fluid. Even more dif­fi­cult is iden­ti­fying where within the PAG itself spe­cific responses originate.

In col­lab­o­ra­tion with researchers at the Mass­a­chu­setts Gen­eral Hos­pital in Boston, Sat­pute and his col­leagues used a high-​​tech fMRI instru­ment that con­tains a seven-​​Tesla magnet. The force of the instru­ment is so strong (albeit harm­less) that one can feel its pull when simply walking by. Cou­pled with painstaking manual data analyses, Sat­pute was able to resolve activity in sub-​​regions of the PAG with more pre­ci­sion than ever before.

With their method in hand, the research team showed 11 human research sub­jects images of burn vic­tims, gory injuries, and other con­tent related to threat, harm, and loss while keeping tabs on the PAG’s activity. Researchers also showed the sub­jects neu­tral images such and then com­pared results between the two scenarios.

The proof-​​of-​​concept study showed emotion-​​related activity con­cen­trated in par­tic­ular areas of the PAG. While sim­ilar results have been demon­strated in animal models, nothing like it had pre­vi­ously been shown in human brains.

Using this method­ology, the researchers said they would not only gain a better under­standing of the PAG but also be able to inves­ti­gate a range of brain-​​related research ques­tions beyond this par­tic­ular structure.

Seven-​​Tesla brain imaging pro­vides an unprece­dented view of regions like the PAG while they respond to stimuli, said Lisa Feldman Bar­rett, director of the Inter­dis­ci­pli­nary Affec­tive Sci­ence Lab­o­ra­tory. “Studies like this are a crit­ical step for­ward in bridging human and non­human animal studies of emo­tion, because they offer a level of res­o­lu­tion in human brains that was pre­vi­ously pos­sible only in studies of non-​​human animal,” she said.

Notes about this neuroimaging research

Written by Angela Herring
Contact: Angela Herring – Northeastern University
Source: Northeastern University press release
Image Source: The image is credited to Ajay Satpute, Northeastern University and is adapted from the press release.
Original Research: Abstract for “Identification of discrete functional subregions of the human periaqueductal gray” by Ajay B. Satpute, Tor D. Wager, Julien Cohen-Adad, Marta Bianciardi, Ji-Kyung Choi, Jason T. Buhle, Lawrence L. Wald, and Lisa Feldman Barrett in PNAS. Published online September 30 2013 doi:10.1073/pnas.1306095110