Parkinson’s disease and deep brain stimulation (DBS) procedures sometimes used to treat it can alter personality, including key traits that make a person, in essence, who they are.

While many patients and families report positive changes, there is a need to better identify exactly what personality characteristics may be affected and to what degree personality is altered. Knowing such information could help clinicians and researchers to provide more concise informed consent, says Cynthia Kubu, PhD, a neuropsychologist in the Cleveland Clinic’s Center for Neurological Restoration.

Kubu recently received a $1.6 million grant over four years to study patients’ and family members’ perspectives regarding personality changes in Parkinson’s disease and DBS. The study is funded by the NIH’s Brain Research through Advancing Innovative Neurotechnology (BRAIN) initiative. The project is now in its fifth year, studying brain disorders like Alzheimer’s, autism, epilepsy, schizophrenia, and traumatic brain injury. A central question is how these conditions affect the brain in terms of altering personality, an area Kubu is keenly interested in as a neuropsychologist.

“What I tend to hear most often from my patients and their family members in the context of Parkinson’s disease — before they have even had the DBS — is that there are no significant [personality] changes. Or they will say he is more withdrawn, more anxious, quieter. There are dimensions of neurological disorders in which personality changes are much more dramatic. That’s because they affect different parts of the brain. In which case, they may be more irritable or short-tempered or inappropriate, but that is a different kind of disorder. This grant is focusing only on patients with Parkinson’s disease.”

The study’s data could be applicable to other conditions, as Kubu tries to discern whether existing measures capture personality characteristics most valued by patients and families.

“We are going to compare — measure, essentially — what the patient and the family members think are most important personality characteristics, and have them kind of rate those and then see how well they are correlated with existing personality measures,” she says. The extent to which the most common existing personality measures really reflect patients’ and families’ values are most important, she adds.

Kubu is recruiting 150 patients with Parkinson’s disease. Each patient will have a family member or a close friend who will participate in the study essentially as an observer of personality changes.

“So, we will have 300 people total enrolled in the study,” she says. “Fifty of those will be within a few years of the diagnosis of Parkinson’s disease; 50 will be five to seven years from their diagnosis of Parkinson’s; and 50 will be those scheduled to have DBS. We will talk to those 50 patients as well their family member or close friend, before surgery, six months after surgery, and 12 months after surgery.”

‘What Trait Would You Least Like to Lose?’

We asked Kubu to provide more detail on this cutting-edge research, particularly as patients and loved ones try to assess whether the subject’s sense of humor, for example, has been affected by the disease and/or the intervention.

IRB Advisor: Can you tell us a little about your background that has led you to this path of research?

Kubu: I am first and foremost a clinician — a neuropsychologist. Neuropsychology is the study of the brain and behavior, and we know certain parts of the brain are important for certain thinking skills. Some parts are important to memory, attention, language, but also aspects of our mood and personality — kind of who we are. Throughout my 25-year career, I’ve worked primarily with functional neurosurgery teams. In the last 18 years, I’ve worked primarily with deep brain stimulation [DBS] teams. My job is to see these patients before they go to have a deep brain surgery. Most people think Parkinson’s disease is mostly a movement disorder — tremors, rigidity, trouble walking, and balance problems. But we know there are a number of non-motor symptoms that can occur with Parkinson’s disease as well, including changes in thinking, mood, or personality.

IRB Advisor: What is involved in DBS?

Kubu: Deep brain stimulation is a procedure in which a tiny hole is drilled into the skull and an electrode is implanted deep in the brain with a connecting cable to something like a pulse generator — it’s kind of like a cardiac pacemaker that’s placed in the chest. You control the stimulation of that electrode to maximize benefit and minimize harm or side effects. The procedure is highly effective in treating the motor symptoms of Parkinson’s disease.

[For the most part], it doesn’t really impact their thinking or the non-motor symptoms. My job with the deep brain stimulation team is to kind of help identify what are the potential risks to these people that go on to have an elective surgical procedure designed to improve their quality of life. That’s where the ethics comes in because it is related essentially to informed consent. The concern I have after seeing thousands of these patients is that the existing measures to look at personality may not capture what is most important to patients and their family members. From the IOM patient-centered care ethical mandate, and from a clinician’s perspective, that is probably what is most important — what is most meaningful to the patient.

IRB Advisor: So, you want to better identify and measure personality changes associated with Parkinson’s disease and DBS?

Kubu: The goal of this study is really to identify the personality characteristics of the patients and, in a separate interview, what their families and friends think are the most important things that really define who the patient is. Then, to see if there are changes associated with Parkinson’s disease and deep brain stimulation on the characteristics that are identified. That feeds into an informed consent issue that is relevant to ethics.

Furthermore, we know from some of the literature, there are some people who think it is bizarre to have an implant in the brain. Some of the literature in the philosophy realm or bioethics has questioned this [in terms of] your surrounding identity. If you’ve got this implant [in your brain], are you really you? There are a few isolated case studies in which patients did show some pretty dramatic changes as the result of stimulation, and that was quickly addressed. The vast majority of people, though, really don’t observe changes — at least, that’s been my clinical experience.

IRB Advisor: How do the data to date inform this topic?

Kubu: What we can say is that some pilot data suggest patients and family members attribute more negative changes to the Parkinson’s disease. Then, after DBS, the majority say they haven’t observed any changes, or if there are changes they tend to be positive and more like who [the patient] was before the disease. In terms of the [personality characteristics] that are most important from the patient and family perspective, about 75% of the patients said they did not see any changes in their personality related to the DBS, and 25% said they are more like they used to be. And that helps in terms of the informed consent decision-making. I think what is unique is that this is very much from the patients’ and the family’s perspective, which is what matters the most.

IRB Advisor: Just to clarify, the NIH grant you received will be used to try and improve the informed consent process and/or review different measures of personality and possibly develop new ones?

Kubu: That is really the issue. My goal is really empirical nueroethics — to use the data to help other DBS teams identify what are personality and meaningful changes that occur in the context of Parkinson’s disease and/or with DBS. That can help better inform clinicians when they go through potential risks, benefits, and side effects, so that there are data to guide that and it also can be used to develop measures that more clearly and accurately reflect patients’ values, which is also ethics and then informed consent specifically regarding deep brain stimulations.

IRB Advisor: So, patients and families may ask if the subject will lose a sense of humor or no longer appreciate some aspect of life that is currently vital?

Kubu: That is the question we are trying to answer. I don’t think there are really very many measures of sense of humor in terms of a personality scale. We are trying to identify what are those big buckets of things that people think are most important. I don’t think it is necessarily going to be how smart you are. It’s going to be, for example, how you interact with other people because I think we are interrelational beings. What are the things that you never want to see that person lose? It could be sense of humor.

We are going to parse out the things that people value most in the humanity of their loved ones. I think some of the same things are going to bubble up to the top. Then, we can start to look at a couple of things. For example, we can design measures that reflect those measures if they don’t already exist. Or, identify personality measures that do reflect those values. Then we can start to look at what are the underlying neuroanatomical correlates as well. Can we use those data to help other patient populations?