Study: Personalized, closed-loop neuromodulation can (one day) become a “pacemaker for the brain”

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Click image above to watch 2‑minute video explain­ing the study

Treat­ing Severe Depres­sion with On-Demand Brain Stim­u­la­tion (UCSF press release):

UCSF Health physi­cians have suc­cess­ful­ly treat­ed a patient with severe depres­sion by tap­ping into the spe­cif­ic brain cir­cuit involved in depres­sive brain pat­terns and reset­ting them using the equiv­a­lent of a pace­mak­er for the brain.

“This study points the way to a new par­a­digm that is des­per­ate­ly need­ed in psy­chi­a­try,” said Andrew Krys­tal, PhD, pro­fes­sor of psy­chi­a­try and mem­ber of the UCSF Weill Insti­tute for Neu­ro­sciences. “We’ve devel­oped a pre­ci­sion-med­i­cine approach that has suc­cess­ful­ly man­aged our patient’s treat­ment-resis­tant depres­sion by iden­ti­fy­ing and mod­u­lat­ing the cir­cuit in her brain that’s unique­ly asso­ci­at­ed with her symptoms.”

Pre­vi­ous clin­i­cal tri­als have shown lim­it­ed suc­cess for treat­ing depres­sion with tra­di­tion­al deep brain stim­u­la­tion (DBS), in part because most devices can only deliv­er con­stant elec­tri­cal stim­u­la­tion, usu­al­ly only in one area of the brain. A major chal­lenge for the field is that depres­sion may involve dif­fer­ent brain areas in dif­fer­ent people.

What made this proof-of-prin­ci­ple tri­al suc­cess­ful was the dis­cov­ery of a neur­al bio­mark­er – a spe­cif­ic pat­tern of brain activ­i­ty that indi­cates the onset of symp­toms – and the team’s abil­i­ty to cus­tomize a new DBS device to respond only when it rec­og­nizes that pat­tern. The device then stim­u­lates a dif­fer­ent area of the brain cir­cuit, cre­at­ing on-demand, imme­di­ate ther­a­py that is unique to both the patient’s brain and the neur­al cir­cuit caus­ing her illness.

This cus­tomized approach alle­vi­at­ed the patient’s depres­sion symp­toms almost imme­di­ate­ly, Krys­tal said, in con­trast to the four- to eight-week delay of stan­dard treat­ment mod­els and has last­ed over the 15 months she has had the implant­ed device. For patients with long-term, treat­ment-resis­tant depres­sion, that result could be trans­for­ma­tive … To per­son­al­ize the ther­a­py, Chang put one of the device’s elec­trode leads in the brain area where the team had found the bio­mark­er and the oth­er lead in the region of Sarah’s depres­sion cir­cuit where stim­u­la­tion best relieved her mood symp­toms. The first lead con­stant­ly mon­i­tored activ­i­ty; when it detect­ed the bio­mark­er, the device sig­naled the oth­er lead to deliv­er a tiny (1mA) dose of elec­tric­i­ty for 6 sec­onds, which caused the neur­al activ­i­ty to change.

The Study:

Closed-loop neu­ro­mod­u­la­tion in an indi­vid­ual with treat­ment-resis­tant depres­sion (Nature Medicine)

  • Abstract: Deep brain stim­u­la­tion is a promis­ing treat­ment for neu­ropsy­chi­atric con­di­tions such as major depres­sion. It could be opti­mized by iden­ti­fy­ing neur­al bio­mark­ers that trig­ger ther­a­py selec­tive­ly when symp­tom sever­i­ty is ele­vat­ed. We devel­oped an approach that first used mul­ti-day intracra­nial elec­tro­phys­i­ol­o­gy and focal elec­tri­cal stim­u­la­tion to iden­ti­fy a per­son­al­ized symp­tom-spe­cif­ic bio­mark­er and a treat­ment loca­tion where stim­u­la­tion improved symp­toms. We then implant­ed a chron­ic deep brain sens­ing and stim­u­la­tion device and imple­ment­ed a bio­mark­er-dri­ven closed-loop ther­a­py in an indi­vid­ual with depres­sion. Closed-loop ther­a­py result­ed in a rapid and sus­tained improve­ment in depres­sion. Future work is required to deter­mine if the results and approach of this n-of‑1 study gen­er­al­ize to a broad­er population.

The Study in Context: