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Brain Region Senses Setbacks, Redirects Action
Confronted with a new construction project on a normally clear street, the average driver will detour around the traffic jam or plot a different route for the next day’s commute.
In devising this strategy, one region of the brain seems to take charge of sensing setbacks and switching to a new course of action. The findings, the first direct human evidence of this localized function, are reported in the December 2004 Nature Neuroscience by a group of neurosurgeons and psychiatrists at Massachusetts General Hospital.
Building on a long history of studying the brain in consenting patients during neurosurgery, (from left) Ziv Williams, Tarek Abuelem, Ramin Amirnovin, and Emad Eskandar have combined direct intraoperative recordings with simple behavioral experiments to analyze normal function and pathological changes in the brain. (Photo by Graham Ramsay)
The study is “an experimental tour de force” for its “remarkable window into human brain function, only rarely available to scientists,” wrote William Gehring and Stephan Taylor of the University of Michigan in an accompanying commentary.
A Surgical Window
The findings come from neuronal recordings of five people who consented to take a few minutes during delicate surgery on their brains to move a joystick to the left or right in response to simple commands on a computer screen.
For the experiment, “$$$$$” flashed on the screen every time patients correctly moved the joystick, rewarding them the highest prize (15 cents) and telling them to repeat the same move. A double arrow, “<>,” indicated a direction change to win the same top prize. Occasionally, “$$$” would pop up, yielding a reduced reward (9 cents) and telling the subjects to change direction for the higher incentive.
The patients performed the tasks before and after a rare procedure called a cingulotomy. The operation had no relationship to the experiment except that with the patients’ consent, it afforded access to a specific region of the brain and a chance for direct evidence of the region’s function. A cingulotomy ablates the tiny area known as the dorsal anterior cingulate cortex. The same thin microelectrodes that helped neurosurgeons Ziv Williams, HMS clinical fellow in surgery, and Emad Eskandar, HMS assistant professor of surgery, precisely define the surgical site also recorded the activity of individual neurons during the brief experiments.
The surgery is a last-ditch effort to treat severe depression, obsessive–compulsive disorder, and bipolar affective disorder when all else seems to have failed. Even in these cases, the problem likely is not in the cingulate, which the study authors believe to be comparatively normal in these patients. Instead, the surgical lesion may disrupt a nearby circuit, leading to gradual clinical benefits three to six months later, presumably emerging as the brain adapts, said co-author Scott Rauch, HMS associate professor of psychiatry at MGH.
Of the total 134 neurons recorded across the five patients, about one third reacted to the direction change signals. Most of these were stimulated by the $$$ reduced-reward cue. Interestingly, the neurons began firing about three seconds before anyone moved the joystick, predicting when people would correctly change direction after seeing $$$, said Williams, first author of the paper.
Other convincing evidence that these neurons are important to this error-monitoring behavior came from data collected after the cingulotomy. Patients showed a dramatic reduction in changing joystick direction in response to the $$$ signal, compared to prompts by the neutral <>. There was no change with $$$$$.
“That tells us they were impaired in their capacity to perceive the reduced reward and to change behavior accordingly,” said Eskandar, the senior author. “Somehow, the cingulate is important in telling a person that a previously fruitful or productive activity is now less so. It may be the part of the brain that tells you something is not working anymore and it’s time to try something new.”
The findings add a new layer of evidence to noninvasive imaging studies, which have implicated this part of the cingulate in detecting errors, monitoring personal conflicts, and performing new behavior.
“Conducted with appropriate care and precaution, studies like this one will be critical in supplementing the more widely available noninvasive tools of cognitive neuroscience,” write Gehring and Taylor.
Eskandar and his MGH colleagues also have applied their pioneering intraoperative recording techniques to explore the pathology behind Parkinson’s disease. In the Dec. 15 Journal of Neuroscience, they report how an experimental task briefly disrupts the pathological signals in the diseased area of the brain. The Parkinson’s study took place in the midst of a therapeutic procedure to implant an adjustable electrode to reduce or modify the abnormal neuronal activity underlying the disease. When the 11 consenting patients used a joystick to guide a green dot to its target on a computer screen, the characteristic abnormal electrical bursts in the dopamine-starved cells of the subthalamic nucleus took on a more normal firing rate. The study was led by Ramin Amirnovin, HMS clinical fellow in surgery.
In both studies, the decisions to perform surgery were based on clinical indications and consultation with clinicians not involved in the research; the decisions were not related to participation in the studies. For the cingulotomies, patients underwent even more extensive review by an independent multidisciplinary committee, said Rauch.
One limit of the studies is the likely stressful surgical setting. And in the cingulate study, “one wonders how much the difference between a 15- and 9-cent reward concerns someone lying in an operating room in the midst of brain surgery,” Gehring and Taylor write.
“It’s a very complicated process,” Williams said. “We don’t presume to know how people are able to make strategic decisions, but we think this area [of the cingulate] plays a significant role in linking those two parts of the world, perception and action.”
— Carol Cruzan Morton