Well-timed pulses from
electrodes implanted in the brain can enhance memory in some people, scientists reported on Thursday, in the most rigorous
demonstration to date of how a pacemaker-like approach might help reduce
symptoms of dementia, head
injuries and other conditions.
The report is the result
of decades of work decoding brain signals, helped along in recent years by
large Department
of Defense grants intended to
develop novel treatments for people with traumatic brain injuries,
a signature wound of the Iraq and Afghanistan wars.
The research, led by a
team at the University of Pennsylvania, is published in the journal Current
Biology.
Previous attempts to
stimulate human memory with implanted electrodes had produced mixed results:
Some experiments seemed to
sharpen memory, but others muddled it. The new paper resolves this confusion by
demonstrating that the timing of the stimulation is crucial.
Zapping memory areas when
they are functioning poorly improves the brain’s encoding of new information.
But doing so when those areas are operating well — as they do for stretches of
the day in most everyone, including those with deficits — impairs the process.
“We all have good days and
bad days, times when we’re foggy, or when we’re sharp,” said Michael Kahana,
who with Youssef Ezzyat led the research team. “We found that jostling the
system when it’s in a low-functioning state can jump it to a high-functioning
one.”
Researchers cautioned that
implantation is a delicate procedure and that the reported improvements may not
apply broadly.
The study was of epilepsy patients; scientists still have much
work to do to determine whether this approach has the same potential in people
with other conditions, and if so how best to apply it.
But in establishing the
importance of timing, the field seems to have turned a corner, experts said.
Experts said the new
report gives scientists a needed blueprint for so-called closed-loop cognitive
stimulation: implanted electrodes that both monitor the functional state of
memory areas, moment to moment, and deliver pulses only in the very
microseconds when they’re helpful.
The hope is that such
sensitive, timed implants could bolster thinking and memory in a range of
conditions, including Alzheimer’s and other dementias, as well as deficits from brain injury.
“The cool thing about this
paper is that they showed why stimulation works in some conditions, and why it
doesn’t in others,” said Bradley Voytek, an assistant professor of cognitive
science and neuroscience at the University of California, San Diego, who was
not involved in the work. “It gives us a blueprint for moving forward.”
Justin Sanchez, director
of the biotechnologies office at the Pentagon’s Defense
Advanced Research Projects Agency, which has doled out some $77 million to
advance cognitive stimulation, said: “To me, this paper is one of the
breakthrough moments on this problem, to find locations in the brain to
stimulate in this particular way to boost performance.”
The new study is the
latest chapter in an extraordinary, decades-long collaboration among cognitive
scientists, brain surgeons and people with severe epilepsy being evaluated for
an operation.
The preoperative
“evaluation” is a fishing expedition of sorts, in which doctors sink an array
of electrodes through the top of the skull and wait for a seizure to occur, to see whether it’s
operable.
Many of the electrodes sit
in or near memory areas, and the wait can take weeks in the hospital.
Cognitive scientists use
this opportunity, with patients’ consent, to present memory tests and take
recordings.
This approach — called
direct neural recording, and piggybacking entirely on the clinical placement of
the electrodes — has become the leading edge of research into the biology of
human memory.
This study used data from
150 patients, and had 20 collaborators from institutions around the country,
including Emory University, the University of Washington, the Mayo Clinic and
the University of California, San Francisco.
In a series of
experiments, the researchers had patients memorize lists of words and later,
after a distraction, asked them to freely recall as many of the words as they
could.
All the while, the
scientists monitored a handful of “hot spots” in the brain which, previous work
had shown, were strongly related to memory encoding.
Before the stimulation tests,
the team determined the precise settings for each patient’s high- and
low-functioning states.
Each participant carried
out the word-memorization tests repeatedly, with different words every time;
some lists were memorized with brain stimulation, and other lists with no
stimulation, which served as a control.
The authors then examined
memory performance based on whether stimulation arrived during low- compared
with high-functioning brain states.
The team then
statistically analyzed the results and found that people scored slightly higher
than usual on words when stimulation arrived during a low or foggy state — and
worse, when the pulse arrived in a high state. “The average enhancement effect
was about 12 to 13 percent,” Dr. Kahana said. “And when stimulation arrived in
a good state, the average was about 15 to 20 percent worse than usual.”
Dr. Doris Greenblatt, a
psychiatrist who participated in the trial at Emory, said she sought the
surgery because her epilepsy had long caused memory problems. “Each seizure I
had tore at the fabric of memory, and it was as if my memories weren’t attached
to anything,” Dr. Greenblatt said.
She agreed to the memory
testing for the study. “It was a little humiliating, to be honest,” she said of
the testing. “I would remember one or two items from a list of objects in a
kitchen, for instance, then think, ‘Oh no, what else was there?’ ”
She said she had no idea
whether the electrodes in her brain were stimulating or not. “All I can say is
that it was exhausting, and I worried about how I was doing.” She had the
surgery for her epilepsy a year ago, with Dr. Robert Gross, and has not had a
seizure since; her memory is also improved, she said.
The timed component in
this study represented a clear break from previous approaches. In 2014 the
Defense Department had funded another group testing stimulation in epilepsy
patients — directly to a brain area near the hippocampus, which is crucial to
memory formation.
That approach did not take
into account brain states, the high and low function, and it was not
successful.
“To me,” said Dr. Voytek,
the new approach “is a clear demarcation that the era of dumb stimulators is
over.”
Source: NY Times
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