Researchers Mix with Clinicians at 2015 NeuroFutures Conference in Portland

by James Cavuoto, editor

July 2015 issue

About 200 neuroscientists, clinicians, and neural engineers from the Northwest and beyond attended the second annual NeuroFutures Conference, held in Portland, OR earlier this month. The event was hosted by Oregon Health and Science University, with support from the University of Washington, the Allen Institute for Brain Science, and the Northwest Neuro Neighborhood.

Keynote speaker Helen Mayberg from Emory University gave attendees an update on her efforts at developing new DBS therapies for depression and other mood disorders. Mayberg alternately expressed frustration and optimism with progress over the last 10 years since publication of her pioneering work with Andres Lozano on DBS of Cg25 for treatment resistant depression. “Things don’t always go exactly the way you thought they would,” she said referencing two failed clinical trials, one sponsored by Medtronic and the other by St. Jude Medical.

Mayberg did not abandon her efforts to treat depression with neuromodulation after the failed BROADEN trial, but instead chose to deconstruct the neural circuits that were active in responders versus nonresponders to DBS therapy. Working with Cameron McIntyre at the Cleveland Clinic, she used DTI tractography to isolate the white matter tracts that were activated by DBS leads and that produced a therapeutic benefit.

It turned out that it was not the Cg25 target that was most relevant, but rather the tracts from there leading to ventromedial prefrontal cortex, nucleus accumbens, and the cingulum bundle. She also discovered that there was a longer recovery period for patients undergoing DBS for treatment resistant depression—data after two years of neuromodulation therapy was better than after three or six months, a finding that was similar to results for vagus nerve stimulation for depression.

Mayberg also found considerable individual variability resulting from branching of white matter bundles. After changing the DBS contact so as to hit all four bundles in each hemisphere, responder rate increased from 41 percent after six months to 85 percent after two years. Mayberg believes that cortical plasticity may play an important role in neuromodulation for depression.

One of Mayberg’s primary goals is to develop biomarkers that not only indicate the presence of a psychiatric disorder such as major depression, but also suggest a therapeutic approach that is most likely to succeed. She has found that metabolic activity in the right anterior insula might be one such biomarker. Patients with decreased rAI activity were more likely to respond to psychotherapy than the pharmaceutical agent escitalopram, while patients with increased rAI activity showed the reverse tendency. Her team has also noted high metabolic activity in subgenual anterior cingulate in patients that do not respond to standard psychiatric treatment, making this subpopulation a potentially rich target for neuromodulation therapies. She is also looking at possible local field potential biomarkers from Cg25 that might be usable in the operating room and she has noticed changes in frontal EEG theta power after one month of therapy that may be clinically meaningful.

With appropriate biomarkers in place, Mayberg would like to see future clinical trials of DBS for depression with more tightly focused endpoints. “With DBS for Parkinson’s you modulate very specific symptoms. We don’t yet do that for psychiatry,” she said. “We don’t have plaques or tangles to measure or tremor that we can observe. But when a patient is profoundly depressed and their sense of being dead goes away, I don’t have a metric for that.” She advises any future neuromodulation vendor targeting depression be in it for the long haul. She would like to see a device that incorporates bilateral stimulation and a closed-loop paradigm that modifies stimulation parameters based on feedback from neural biomarkers.

In another talk, Don Tucker from Electrical Geodesics described his firm’s high-density EEG system and its use with a new tDCS system from the company. “We can’t imagine why you would want to do fMRI anymore,” he said, only partly in jest. EGI seeks to use EEG as a guide for neuromodulation therapy.

Terry Sejnowski from the Salk Institute described several different levels of investigation of the brain, which he said incorporates 11 orders of magnitude. Looking at EEG sleep recordings, he suggested that stage 2 sleep spindles in the 11 Hz range might be involved with consolidating memory. His team developed a coupled oscillator model of sleep spindles based on interplay between excitatory and inhibitory cells in the thalamus.

Robert Greenberg from Second Sight Medical gave attendees an update of his firm’s efforts in visual prostheses. He said the company’s Argus II retinal prosthesis system is currently reimbursed by CMS in most regions of the U.S., although there is no national coverage decision in place. The company is currently building 10 units per month but is capable of ramping that up to 100 units per month, he said.

Greenberg also described the company’s Orion 1 cortical stimulation system for treatment of blindness. The system is currently in animal trials with human trials slated to begin next year.

Dan Rizzuto from the University of Pennsylvania described his institutions’s efforts in DARPA’s Restoring Active Memory program, which includes eight clinical centers using memory testing and brain stimulation. Thus far, 69 patients have participated in 250 sessions.

Rizzuto noted that 50 Hz stimulation of the hippocampus appears to impair verbal memory on average. But he also noted that the effect of stimulation is variable across subjects and is developing a biomarker that may help identify patients likely to benefit from stimulation. The classifier is based on the relative theta and gamma power gathered from intracranial recording 400 milliseconds after the presentation of a stimulus.

Carlos Pena, the director of the CDRH’s division of neurological and physical medicine devices, described the makeup of the new FDA division. He described a new program for accelerating approval of devices targeting life-threatening or irreversibly debilitating disorders.