Psychiatric and neurological disorders from depression to schizophrenia to Alzheimer’s all seem to be marked by abnormalities in the brain’s electrical patterns. These diseases, which are notoriously difficult to treat, have shown responses to various kinds of electrotherapy, from deep brain stimulation, which involves the placement of electrodes inside the brain itself, to electroconvulsive therapy (so-called “shock treatment”), which causes a seizure in an effort to “reset” the brain.
Frohlich brings to his research a somewhat unusual background that would seem to make him especially suited to this line of work—he trained as an electrical engineer before pursuing a PhD in neurobiology.
“What really causes symptoms [in neurological and psychiatric diseases] and what allows us to walk and talk and dream are the synchronized tiny little electric impulses generated by our brain,” he says. “When we think about the disease process, and therefore potential treatment targets, we think less of receptors and molecules, and more of large-scale electricity patterns in the brain.”
In the two-day study, 16 participants were asked to do two memory exercises at night. Then, before going to sleep, they were fitted with electrodes at specific spots on their scalps. One night, the patients received tACS through the electrodes. On the other night, they got a sham stimulation. Both mornings, they repeated the same memory exercises. The results of one of the exercises (though not the other) improved dramatically after stimulation as compared with the placebo.
“Essentially if you look at the [memory] gain you get just by sleeping—and you do get a memory benefit just from sleeping—when we stimulated, it was almost twice as much,” Frohlich says.
The tACS targeted what’s known as the “sleep spindles,” waves of brain activity believed to aid in storing memories during sleep. In the study, the more the spindles were stimulated, the greater the memory enhancement in the morning.
The stimulation used in the study differed from standard tACS in that it was feedback controlled. The device was programmed to detect sleep spindles in real time and apply stimulation accordingly. This type of tACS enhancement has exciting potential for individualizing treatment, Frohlich says. Brain activity, he explains, changes from moment to moment, and varies widely from individual to individual. The next generation of tACS could take that into account, predicting and responding to brain changes dynamically.
“It works like a thermostat,” he says. “You know what you want the room temperature to be, and as it fluctuates the thermostat turns on the heat or AC to regulate the temperature.”
The 16 study subjects were all healthy. But, since memory formation is impaired in various psychiatric disorders, the team reasons this treatment may be applicable to those with these disorders as well.
“My vision is that we can develop truly novel effective treatments for serious mental illnesses such as depression and schizophrenia,” Frohlich says. “The advantage of tACS is that the actual required hardware is essentially portable, so we and also others have started to think about how to make that technology deployable to the home, perhaps through remote online supervision or monitoring.”
But this, he cautions, may be well down the road.
“This is exciting research, but it’s a first study,” he says. “As with any good science, the results need to be replicated. This is really early days.”
The study, whose first author was postdoctoral researcher Caroline Lustenberger, was recently published in the journal Current Biology.
Frohlich is currently running two clinical trials using tACS, one on depression and one on schizophrenia. Both of these trials involve standard tACS treatment, without the newer feedback loop process. Frohlich hopes to bring that process to clinical trials in the near future.