From: [log in to unmask] [mailto:[log in to unmask]] On Behalf Of Now@NEJM
Sent: February 08, 2012 19:04
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Subject: Now@NEJM: Memory Enhancement and Deep-Brain Stimulation 

Now@NEJM: Memory Enhancement and Deep-Brain Stimulation 


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Memory Enhancement and Deep-Brain Stimulation 
Posted: 08 Feb 2012 02:00 PM PST
We all fear forgetting. Go out with the stove left on, forget your house keys, lose your way in a familiar neighborhood. These common events provoke both annoyance and deep worry: Are these the first signs of Alzheimer’s? Will my memory worsen until I can’t even remember my family, or my own self?
Scientific understanding of memory, and its loss, has been so murky that memory loss caused by Alzheimer’s or other types of dementia have long remained a veritable black box. Even the medications aimed to slow the progression of memory loss have limited success.
In recent years, however, brain imaging and electrophysiology have led to improved understanding of the mechanism of memory formation. Largely through animal studies, scientists have shown the brain’s medial temporal structures – specifically the hippocampus and entorhinal cortex – to be essential for memory formation. Furthermore, studies of patients with neurologic disorders have established deep-brain stimulation to be a valuable technique to modify brain function.
With this background, Dr. Nanthia Suthana and colleagues posed the question whether deep-brain stimulation in specific zones improved memory.
Their provocative answer, published in this week’s NEJM:  Yes, it can.
In their study, the researchers enrolled seven patients with epilepsy that had not been responsive to medication. All were already going to receive intracranial electrodes for 7 – 10 days to determine the site of seizure onset.   Based on clinical criteria, six of these seven patients had electrodes implanted in the entorhinal cortex, five had electrodes implanted in the hippocampus and four had electrodes in both these regions.
The researchers then set out to explore how stimulating these electrodes affected memory formation. To this end, all subjects were asked to complete a task where they had to navigate through a virtual town on a computer. The task was split up into different sessions, where participants learned routes to a number of virtual stores. In some of the learning blocks, the electrodes were stimulated; in others, they weren’t.  After a 2-minute control interval, the participants then had to navigate to each of the stores without any electrode stimulation.
What the researchers found, notably, was that the participants were better able to navigate their way to a virtual store whose route they’d learned while undergoing electrode stimulation of the entorhinal cortex. Patients were graded on their ability to navigate quickly and use the most direct route.
On average, there was a 64% reduction in “excess path length” (circuitous wandering before arriving at the goal destination) for locations that had been learned while the patients received entorhinal stimulation. On the contrary, stimulating the hippocampus did not result in a consistent effect.
The authors conclude that their results “show that spatial learning in humans can be enhanced by electrical stimulation of the entorhinal area.” They do note, however, that their study subjects all had epilepsy and thus it remains unclear how the results could be applied to other populations.  It is also not known how, and whether, such stimulation can improve retention of other types of learning, like verbal or autobiographical. Furthermore, stimulation was applied specifically during the learning phase in this study; it’s not clear whether stimulation during the act of recall could improve performance.  Finally, it’s not known how long the benefits of stimulation persist.
However, the results hold promise, writes neurologist Sandra E. Black in an accompanying editorial. She notes that while the findings need replication in larger and more heterogeneous cohorts, they might hold promise for patients suffering from a wide range of neurologic disorders affecting memory.
While deep-brain stimulation would likely not benefit patients in the end stages of Alzheimer’s dementia, according to Black, there could be applications earlier on in the disease process. Alternately, patients with injuries to the hippocampus who suffer memory impairment might, one day, also benefit from applications of this technique.
“Although current evidence is preliminary,” Black writes, “the potential application of deep-brain stimulation in amnestic disorders is enticing.”



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