by Angela Herring

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.

“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.

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

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 PAGwith 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.

Originally published in news@Northeastern on October 3, 2013.