Damasio’s hoarders also had damage in the anterior cingulate, the structure that in OCD patients screams something is wrong. But the hoarders’ anterior cingulates were remarkably quiet. It apparently detected nothing amiss whatsoever, despite goat paths and ceiling-high piles of stuff. In contrast, subcortical structures that, in lab rats, drive the animals to acquire and retain objects were unimpaired. That led the Iowa team to posit that hoarding arose in their brain-damaged patients because the prefrontal regions that usually ride herd on acquisition were sidelined by injury. Result: “the drive to collect food and other objects operates without its usual acquired cognitive constraints,” the scientists wrote, resulting in a “disinhibited hoarding drive running relatively free.”
Free indeed. One of the volunteers, a sixty-nine-year-old housewife with a damaged frontal cortex, filled a two-car garage with mostly broken furniture, appliances, lawn ornaments, pet supplies, and clothing scrounged from neighbors’ trash piles. She never tried to use or repair the items. “Her closets and drawers were overflowing,” the Iowa team wrote, “and more clothing . . . was stacked throughout the house.” When a twenty-seven-year-old was left with damage to the frontal cortex, after neurosurgery to repair a brain aneurysm, he began collecting tools, wire, and scrap metal, also from neighbors’ trash, filling his basement and garage. A welder who also sustained frontal damage developed a behavior akin to the bullet collector’s: he felt compelled to collect grains of corn scattered in fields near his home after the harvest (this was Iowa, remember). “He collected corn almost daily,” the scientists wrote, “accumulating large piles and continuing to collect as it rotted and attracted rodents. . . . He also began to bring home found scrap metal and discarded automobile and appliance parts.”
The Iowa study identified structural anomalies in the brains of people who suddenly became hoarders. To glimpse the mental activity hoarders engage in when faced with the decision at the core of their disorder—keep or toss?—required looking for functional anomalies.
A study a few years later did just that. In research presented to the 2007 meeting of the American College of Neuropsychopharmacology, UCSD’s Saxena also found that the anterior cingulate seems to be functionally AWOL in hoarders. He performed neuroimaging on twenty compulsive hoarders and eighteen healthy controls. Compulsive hoarders had significantly lower activity in the anterior cingulate than controls. The worse the hoarding, the lower the anterior cingulate activity, Saxena found: “It’s as if in ordinary circumstances, like looking at the condition of their home, they can’t tell something is wrong.”
But was that lower activity causally related to hoarding? To find out, psychologist David Tolin of the Institute for Living in Hartford, Connecticut, and his colleagues performed an ingenious experiment. They had forty-three compulsive hoarders, thirty-one people with OCD, and thirty-three healthy people come to their lab with a few of their belongings, such as junk mail or an old newspaper. While lying in an MRI tube, the volunteers watched a video screen display one piece of junk mail or newspaper at a time, interspersed with papers belonging to the researchers, in each case preceded by a screen with the word yours or ours so the volunteers did not waste time discerning who that old receipt belonged to. (Tolin has also done the experiment with other possessions, such as empty food containers and toys.) In each case, he asked: Should the assistant shred this one? How about this one? Or this? These were actual, real-time decisions, not a lab game: if the volunteer gave the okay the item would be shredded in front of their eyes. They had six seconds to decide.
Not surprisingly, the hoarders chose to discard significantly fewer of their own possessions than the OCD patients or healthy volunteers did, Tolin’s team reported in 2012 in JAMA Psychiatry. The amount of anxiety, indecisiveness, and sadness the hoarders said they felt while making their decisions was much greater than the OCD and healthy participants felt. And the more anxiety, indecisiveness, sadness, and “not just right” feelings they experienced, the fewer of their possessions they agreed to have shredded.
For the most part, the pattern of activity in the hoarders’ brains resembled that of nonhoarders. There were two screaming exceptions, however: the functional MRI picked up distinctive patterns of activity that seemed to underlie the distress the hoarders reported from deciding whether or not to allow their papers to be shredded. When hoarders had to pick “save or toss” for the researchers’ papers, there was relatively low activity in the anterior cingulate cortex, the region Damasio and Saxena had identified as being damaged or indolent in many hoarders.
When the hoarders in Tolin’s fMRI looked at their own stuff and had to decide to keep it or toss it, activity in the anterior cingulate and insula soared, both compared to baseline and to healthy brains. The more severe the hoarding, the greater the activity spike. In addition, the higher hoarders rated their sense of indecisiveness (What should I do? I know I should say it’s okay to shred that ancient envelope, but . . . ) and the severity of their “not just right” feeling, the higher the insula and anterior cingulate activity.
The finding of increased activity in the anterior cingulate may seem to contradict the Saxena and Damasio finding that hoarders have abnormally low activity there. But remember that those observations were made when the hoarders’ brains were essentially in neutral, not being asked to think about anything. In the Tolin study, hoarders’ brains were forced to judge whether something was or soon would be amiss, namely, whether giving the okay to shred a dearly beloved supermarket circular was a mistake of cataclysmic proportions. Under these circumstances, the anterior cingulate behaved like a teenager who’d slept all day and awoke half an hour before a big test, exploding with frantic activity as if to make up for lost time. The anterior cingulate seemed to say, My job is to assess whether something is wrong in a situation, and the situation is that you’re asking whether it’s okay to toss that old paper? Hell yes, there’s something wrong! The hoarders felt anxious and afraid they’d make a misery-inducing decision. The anterior cingulate screamed, “Mistake! Mistake!” at full volume.
As for the insula, this structure deep in the folds of the cortex had long been a mystery, with conflicting findings about its function. Damasio finally cracked the secret: the insula processes and interprets bodily sensations, such as a fast heart rate and sweating, and links it to an emotion—in this example, anxiety. The insula also seems to assess the emotional salience of stimuli, monitor errors, and evaluate risks. To anthropomorphize, the insula takes input about bodily states linked to emotional experiences, figures out what emotions triggered the bodily state (fear, euphoria, anxiety . . . ), and then sends its conclusions to higher-order cognitive regions so you consciously think, Hmmm, my heart is racing, I must be nervous. This likely comes into play when hoarders are forced to decide whether to condemn long-held papers to capital punishment in a shredder. Their first reaction is anxiety, which leaves a somatic imprint, perhaps a racing pulse. The insula receives that input and translates it into “the emotion in play here is anxiety.”
Together, the anterior cingulate and insula are “at the core of a ‘salience network,’ ” Tolin and his colleagues wrote. Low activity in this network contributes “to the diminished motivation and poor insight frequently observed in patients with hoarding disorder.” Unable to distinguish the significant and worthwhile from the trivial and worthless, they keep and value all of it. But when hoarders are confronted with possessions they have already accumulated, these regions become hyperactive, producing a feeling that something is not right, a sense that you are in danger of making the wrong decision. Hence the decision to keep, save, hoard.
At least one more brain region underlies hoarding. For a 2008 study in Molecular Psychiatry, researchers at King’s College London had twenty-nine OCD patients (thirteen with and sixteen without hoarding symptoms) and twenty-one healthy controls lie in an MRI tube. The volunteers viewed three types of pictures: of objects commonly hoarded by patients (old magazines and newspapers, em
pty food containers, clothes, and toys), of scenes that healthy volunteers had rated highly disgusting and anxiety-provoking (mutilated bodies, spiders, cockroaches, human waste), and of neutral or mildly positive scenes (furniture, nature, pets).
When viewing photos of hoarded stuff, which they were instructed to imagine belonged to them, hoarders showed greater activation (compared to nonhoarders) just behind the forehead, in a structure called the ventromedial prefrontal cortex. That was intriguing, for this region has two key functions: it is decision-making central, and it suppresses emotional reactions to negative images, thoughts, and experiences. In the latter role, you can think of the ventromedial prefrontal as the comforting mother who tells an upset child, There, there, it’s not so bad—or, in the case of hoarders seeing junk, Don’t worry about the grease on that old pizza box; we can clean it up and use it to store newspapers! As a decision-maker, the ventromedial prefrontal is especially important in making choices in situations where the outcomes are uncertain, ambiguous, or possibly risky. In the hoarders, it was as if this structure were frantically trying to figure out whether to be upset about the theoretical annihilation of hoarded stuff even though it belonged to a stranger, and simultaneously trying to quiet the anxiety provoked by the instruction to imagine it as their own and being ordered to toss it.
I wish I could describe comparable neuroimaging research on compulsive shoppers, exercisers, gamers, and Internet surfers. Unfortunately, the few studies that have been done have used so few volunteers, have not been replicated, or have used such questionable designs that they tell us almost nothing. For instance, a 2011 study in the Journal of Consumer Policy imaged the brains of twenty-three compulsive shoppers when they were shown things for sale, when they were shown the price, and then when they decided whether or not to buy. Seeing the item, the shoppers had higher activity (relative to controls) in the nucleus accumbens, a key part of the dopamine circuit, Gerhard Raab of Germany’s Ludwigshafen University of Applied Sciences and colleagues reported. Seeing the price, the shoppers showed relatively lower activation of the insula (which interprets the emotional reasons behind bodily states such as a racing heart) and the anterior cingulate, the error-detection structure that is hyperactive in OCD. That might lead you to craft a story of compulsive shoppers getting deliriously excited when anticipating acquiring a shiny new bauble, and not caring about price, perhaps lacking the neural machinery to judge an item’s value. Except for one thing: when the volunteers decided whether or not to buy, the anterior cingulate became more active. Again, it’s all too easy to glibly explain that compulsive shoppers’ error detectors finally kick into gear . . . but a finding of lower anterior cingulate activity at the point of making a purchase decision would inspire an equally reasonable-sounding explanation (“they can’t tell when they’re about to make a mistake”). Without an a priori hypothesis about the brain activity behind a behavior, neuroimaging becomes a fishing expedition where you can’t tell if the catch is a prized marlin or an old boot.
When Yale’s Marc Potenza and Robert Leeman reviewed the neurobiology of behavioral addictions and compulsive behaviors in the Canadian Journal of Psychiatry in 2013, their account was shot through with warnings like “there have been seemingly opposing results” and diplomatic caveats like “methodological details may contribute to these differing results.” The only safe thing to say about compulsive behaviors is that they probably involve dysfunction of the brain’s dopamine-fueled reward circuits. Fortunately, that’s something where the science has a decades-long foundation to stand on.
The Strange Case of the Parkinson’s Patients
At one level, the neurobiology of compulsions runs on conditioned learning, the kind discovered by Ivan Petrovich Pavlov (1849–1936). The Russian physiologist was studying the digestive system, using dogs as his laboratory model, when he noticed that food caused the canines to salivate. But so, too, did the mere arrival of a lab worker. Since every time food appeared an assistant in standard scientific attire also arrived, Pavlov hypothesized, perhaps the dogs were reacting to the lab coats. In a series of experiments, he identified the conditioned stimulus and response. Most famously, Pavlov rang a bell when the dogs were fed. The dogs learned to associate the ringing, another conditioned stimulus, with food. After a few rounds of this the mere sound of the bell, with nary a scrap of meat in sight, triggered drooling.
People in the grip of a compulsion are like Pavlov’s drooling dogs. A compulsion pairs an urge to get rid of a painful emotion—anxiety—with a behavior that succeeds in doing that. Anxiety about missing an important text is vanquished by constantly checking your smartphone. The receding of that anxiety becomes paired with the behavior: voilà, conditioned learning. That’s the argument Szymanski was making when he explained that giving in to an OCD compulsion relieves anxiety, teaching the brain to do so.
But the desperation and anxiety that drive compulsive behavior can’t be explained by Pavlovian conditioning alone. Patients with Parkinson’s disease, of all things, revealed that something else is going on.
For reasons known only to the gods of evolution, the neurochemical dopamine has jobs in the brain as different as driving a bus and cooking meth. In the substantia nigra, a structure near the base of the brain, dopamine carries signals that allow smooth, controlled movement. When dopamine-producing neurons die, the result is tremors in the hands, arms, legs, jaw, and face; and impaired balance and coordination—Parkinson’s disease. Dopamine is also responsible for sending you to the moon and back during the most mind-blowing orgasmic experiences. That’s because it operates not only in the substantia nigra but also within the reward circuits, which are centered on the nucleus accumbens (of OCD infamy). These circuits calculate how rewarding an experience feels compared to how rewarding you expected it to be. Experiences that meet or exceed expectations feel great, bringing the brain a sense of reward.
You can imagine the possibilities for crossed wires in these quite separate movement and reward systems. Pharmacologists didn’t.
For decades physicians had treated Parkinson’s disease with the drug levodopa, which is a precursor to dopamine. The idea is that if you feed the brain lots of dopamine precursor, it will churn out more dopamine, sort of like turbo-charging deliveries of flour and sugar to a bakery might yield more cupcakes. In the 1990s, however, a new class of drugs was introduced. Called dopamine agonists, they are, like levodopa, also essentially replacement therapy. But they act further downstream, fitting into dopamine receptors. At the risk of belaboring the analogy, it would be like getting customers to eat the sugar and flour directly, without waiting for the ingredients to be baked into cupcakes.
Once a dopamine agonist docks with a dopamine receptor, it triggers an over-the-top reaction. Think of it as plugging a little 1970s-era clock radio into an outlet, getting tinny sound, then one day plugging in a 400-watt guitar amplifier instead, and the first chords of “Smoke on the Water” blow out your eardrums. That’s what taking a dopamine agonist is like: same receptor, different molecular entity plugged in, super-charged result. “Dopamine agonists act on receptors like a superdopamine,” said psychiatrist Michael Bostwick of the Mayo Clinic in Rochester, Minnesota. “They glom on.”
Easy to say now. But in September 2000, a team of neurologists and psychiatrists at Hospital Universitario Doce de Octubre in Madrid, Spain, reported that ten of their levodopa-treated Parkinson’s patients had suddenly become pathological gamblers. Slot machines were the preferred vice. That suggested “it could be related to the dopaminergic” treatment, Dr. José Antonio Molina and his colleagues wrote in the journal Movement Disorders. This hint of a link between sudden compulsive gambling and dopamine drugs had “apparently never been reported” before.
But something close had been. In 1989 neurologist Ryan Uitti and colleagues found that thirteen of their Parkinson’s patients developed hypersexuality soon after beginning levodopa therapy. His discovery, however, appeared in a low-profile journal, Clinical Neuropha
rmacology, and attracted little notice. And over the course of just two weeks in 1999, neurologist Mark Stacy, then director of the Muhammad Ali Parkinson Research Center in Phoenix, learned that two of his Parkinson’s patients, whose medication he had just increased, immediately went on a gambling spree and lost $60,000 each. But he presented the observation in a poster at the Movement Disorders Meeting, not publishing a paper until 2003.
By then, the new generation of dopamine agonists had been in use for nearly a decade, which might make it seem odd that compulsive behaviors were not linked to the drugs until 2000. “But it just wasn’t something you asked,” said neurologist Erika Driver-Dunckley. “Patients would come in and you’d ask about their movement disorder. Why would it occur to anyone to ask if a Parkinson’s patient had suddenly developed compulsive urges to gamble or look at porn?”
After the Spanish report, however, neurologists started both asking and scrutinizing their old notes. At the Muhammad Ali Center, Driver-Dunckley and Stacy began combing through the database of Parkinson’s patients seen from May 1, 1999, to April 30, 2000. Presto: of 1,281 taking dopamine agonists, nine had also mentioned a sudden onset of compulsive gambling, they and their colleagues reported in the journal Neurology in 2003.
That small incidence didn’t exactly constitute an epidemic, but remember that this was a look-through-the-files, retrospective analysis limited by the “don’t ask, don’t tell” quandary that Driver-Dunckley alluded to: neurologists had no more reason to ask a Parkinson’s patient if he had started feeling inexorably drawn to casinos than an ophthalmologist had reasons to ask about bunions. Once she did start asking, Driver-Dunckley told me, “Patients would bring up that they’d gone through a divorce because they’d cheated with a prostitute, or that they’d lost all of their money gambling. That was unusual enough by itself, but even more so because Parkinson’s patients have been described as goody-two-shoes”—straitlaced, risk-averse people whose dwindling supply of dopamine leaves them bereft of the brain signals that deliver hedonic hits. “After just a couple of cases I thought, huh, this might be significant,” she continued. “They weren’t telling me they had spent a little more money gambling than they usually did. It would be, ‘I just spent all of my retirement savings gambling.’ Some blew it all in a week, and some did it by going to casinos every week for a month. But it wasn’t just gambling and hypersexuality. We also had people who developed compulsive hair combing or house cleaning.”
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