Wednesday, December 06, 2006

I Should've Forgotten That

The illustration above is from a brand new paper by Feredoes, Tononi, and Postle that used the latest in transcranial magnetic stimulation (TMS) technology to transiently disrupt bits of cortex (targeted regions indicated by markers) during a verbal working memory task. They were particularly interested in a phenomenon called proactive interference, in which previously remembered information infereres with the ability to remember new material. Overcoming PI involves the inhibition of recently remembered but currently irrelevant information.

Now back to TMS. The authors used repetitive TMS (rTMS) to test whether the left inferior frontal gyrus (IFG) was necessary for overcoming proactive interference. [They had their reasons for suspecting this, based on the existing literature.] They also applied rTMS to brain regions that were not expected to affect proactive interference (postcentral gyrus, motor cortex, and supplementary motor area) to control for non-specific effects.

Here's the coolest part (my emphasis):
rTMS was delivered with a Magstim Standard Rapid magnetic stimulator fit with a 70 mm figure 8 air-cooled stimulating coil (Magstim Co., Whitland, Wales, U.K.). Localization of the stimulating coil was accomplished via infrared-based frameless stereotaxy (eXimia Navigated Brain Stimulation, Nexstim, Helsinki, Finland). For each subject resting motor threshold (MT) was determined as the intensity at which single pulses applied over the hand area of right M1 produced a visible muscle twitch in five out of ten consecutive trials.
eXimia NBS Navigation System, as featured in Medgadget!

The results conformed to their prediction [but you might not believe it based on the figure below, particularly since non-rTMS performance in the left PCG condition was so poor]: rTMS over left IFG (but not other areas) impaired accuracy on working memory trials in which proactive interference was an issue (denoted by blue arrows), but not on other types of trials.

Feredoes E, Tononi G, Postle BR. (2006). Direct evidence for a prefrontal contribution to the control of proactive interference in verbal working memory. Proc. Natl. Acad. Sci. Published online before print December 6, 2006.

Controlling the effects of proactive interference (PI), the deleterious effect of prior mental activity on current memory representations, is believed to be a key function of the prefrontal cortex. This view is supported by neuroimaging evidence for a correlation between the longer reaction times caused by high PI conditions of a working memory task and increased activity in left inferior frontal gyrus (IFG) of the prefrontal cortex. An alternative that has never been ruled out, however, is that this left IFG effect may merely reflect sensitivity to such nonspecific factors as difficulty and/or time on task. To resolve this confound, we applied the interference methodology of repetitive transcranial magnetic stimulation (rTMS) to the left IFG and two control regions while subjects performed delayed letter recognition. rTMS was guided with high-resolution magnetic resonance images and was time-locked to the onset of the memory probe. The effect of rTMS, a disruption of accuracy restricted to high-PI probes, was specific to the left IFG. These results demonstrate that unpredictable, phasic disruption of the left IFG selectively disrupts control of responses to high-conflict verbal working memory probes, and they conclusively reject nonspecific alternative accounts.
And below is what the authors have to say about their study in the popular press:
Controlling confusion -- Researchers make insight into memory, forgetting

. . .

"Psychologists have known for decades that the intuitive notion of decay is probably less of a factor in forgetting than is interference," he says. Interference occurs, he says, when "other remembered information disrupts, competes with or confuses the information that you want to remember."

Interference is always present, Postle says, but we don't always notice it.

. . .

In the current study, volunteers read a group of letters ("F, B, P, X"), and were asked a few seconds later whether a particular letter had appeared in the most recent group (Did you just see a "Z"). In this type of test, having seen a "Z" in the string-before-last causes interference that makes the task more difficult. The subjects take longer to respond, and are more likely to incorrectly say "yes."

The research set-up was designed to be a simplified version of many everyday memory challenges, says Postle. Without a good sorting mechanism, our brains would be utterly confused by the vast amount of observations, ideas and memories that we have stored away. We might, for example, dial the phone number of the friend we just called rather than the one we intended to call.

In previous studies of interference, the IFG consistently lit up in brain scans, showing that it does something when the memory tries to deal with interference. But the IFG could simply be contributing some type of generic processing power to the task, says Postle.

However, the new study proved that the IFG is essential to blocking interference, he says, because accuracy plummeted when the IFG got a brief jolt of magnetic stimulation at the exact moment when the subject was confronting confusion.

Eventually, Postle hopes that locating the site of specific memory operations in the brain may help the millions of people with declining memories. "Understanding how the brain controls interference may be a first step to helping people with memory problems," he says.

The precise system used to target the magnetic pulse has many other applications in neuroscience research and treatment, Tononi adds. "TMS can be used not only to disrupt brain activity, but also to change it. If applied repeatedly, TMS can strengthen certain circuits that have become pathologically weak," he says.

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