Your brain is supposed to fire a “hold your horses” signal when faced with a tough choice. But a brain implant that stops the tremors of Parkinson’s disease may block that signal — a new explanation for why some Parkinson’s patients become hugely impulsive.
Scientists have long known that anti-Parkinson medications occasionally spark compulsions like pathological gambling.
Research published Thursday found another treatment, a pacemaker-like brain implant, can trigger a completely different kind of impulsiveness. How different? The drugs leave a subset of patients unlikely to learn from bad experiences, like a losing poker hand.
The brain implant doesn’t hinder learning. In contrast, those patients can make hasty decisions as the brain loses its automatic tendency to hesitate when faced with conflict, University of Arizona researchers reported online in the journal Science.
In fact, the first patient they studied displayed an alarming example when he saw something across the room he wanted and tried to dash over without his wheelchair. Neuroscientist Michael Frank had to catch the man before he fell.
“Deep brain stimulation,” or DBS, involves placing electrodes into a small region called the subthalamic nucleus, an area important for controlling movement. But it also is where scientists believe the brain yells: “Stop, weigh your options!”
Frank’s theory: When electrodes fire to disrupt excessive movement, they also may block that signal.
“It makes a lot of sense,” said Dr. Valerie Voon, a psychiatrist with the National Institutes of Health’s neurology center, after reviewing the research.
The study doesn’t offer easy solutions. But it could affect how neurologists counsel Parkinson’s patients after DBS surgery.
“Because they don’t have those brakes in place, you need to teach someone to slow down” when faced with certain decisions, Voon said.
At least 1 million Americans have Parkinson’s, suffering increasingly severe tremors and periodically stiff or frozen limbs as brain cells quit producing dopamine, a chemical crucial for movement. There is no cure. Standard treatments include medications to stimulate dopamine and, once those fail, DBS surgery to control tremors.
Doctors have long noticed varying degrees of impulsiveness in Parkinson’s patients, from making uncensored remarks to rare cases of extreme behavior such as compulsive gambling, shopping, eating or sex. Changing medications or doses often solves extreme symptoms — if patients or their families report the worrisome behavior.
Frank wondered what role the brain implant plays.
His team used specialized computer games to probe decision-making in 15 Parkinson’s patients taking dopamine drugs, 17 others who received DBS, and 14 healthy older adults.
First, participants were shown pairs of Japanese characters and told to pick the “correct” one. It was baffling — what makes one symbol better, especially if you don’t know Japanese? But as the computer screen beamed back “Correct!” or “Incorrect!” their brains learned to prefer some characters over others.
Then Frank paired the symbols differently: “Correct” ones together to simulate “win-win” decisions; “incorrect” pairings to model choosing the lesser of two evils; and easy “right-wrong” pairs.
Healthy people and Parkinson’s patients on dopamine drugs hesitated briefly when faced with win-win or lose-lose choices, allowing time to weigh options. But DBS patients didn’t hesitate with lose-lose choices — and actually sped up win-win decisions.
Remarkably, switch off the brain implant and DBS patients quit rushing the close calls.
As in previous research, medicated patients were less likely to learn which “wrong” symbols to avoid, backing the theory that dopamine drugs can hinder learning from negative feedback.
But do the DBS patients’ hasty choices really matter in a win-win situation, where there’s no clearly wrong answer?
In the real world, definitely, said Arizona’s Frank. Say your job offers a range of 401K options. Sure, any one is better than no investment, but just grabbing the first one might not be the most lucrative.
It hasn’t been obvious that different treatments cause different impulsive behaviors, said Dr. Kathleen Shannon of Chicago’s Rush University Hospital.
“They all seem to make bad decisions and have trouble making decisions,” she said. Now, “I’ll start to look at my patients differently.”
What is Parkinson’s Disease?
Parkinson’s disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. PD usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of PD patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions. There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.
Is there any treatment?
At present, there is no cure for PD, but a variety of medications provide dramatic relief from the symptoms. Usually, patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of parkinsonian cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity. Other drugs, such as bromocriptine, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. In May 2006, the FDA approved rasagiline to be used along with levodopa for patients with advanced PD or as a single-drug treatment for early PD.
In some cases, surgery may be appropriate if the disease doesn’t respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In DBS, electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work correctly.
What is the prognosis?
PD is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. Although some people become severely disabled, others experience only minor motor disruptions. Tremor is the major symptom for some patients, while for others tremor is only a minor complaint and other symptoms are more troublesome. No one can predict which symptoms will affect an individual patient, and the intensity of the symptoms also varies from person to person.
What research is being done?
The National Institute of Neurological Disorders and Stroke (NINDS) conducts PD research in laboratories at the National Institutes of Health (NIH) and also supports additional research through grants to major medical institutions across the country. Current research programs funded by the NINDS are using animal models to study how the disease progresses and to develop new drug therapies. Scientists looking for the cause of PD continue to search for possible environmental factors, such as toxins, that may trigger the disorder, and study genetic factors to determine how defective genes play a role. Other scientists are working to develop new protective drugs that can delay, prevent, or reverse the disease.