A patient with frontotemporal dementia discovers his grandson’s birthday cake in the fridge. He doesn’t think twice before getting out a knife and fork and eating every last piece an hour before the birthday party is set to begin.
For patients with this early-onset neurodegenerative disease, some of the first symptoms are a profound loss of inhibition and empathy, which leads to a change in social behaviour that is completely out of character.
“He wasn’t thinking about his grandson at all; and typically, that loss of empathy extends even for those things where empathy is usually most robust, for example toward pets or grandchildren,” said Dr. Elizabeth Finger, associate professor at Western University’s Schulich School of Medicine & Dentistry and a neurologist at St. Joseph’s Health Care London.
Finger is working with scientists at Robarts Research Institute to find ways to restore some of that empathy in patients with frontotemporal dementia (FTD), which she hopes will also reduce social apathy and improve quality of life for the patient and their families.
FTD is the second most common cause of early onset neurodegenerative dementia, and typically starts before the age of 65. Finger says it is also under-recognized because it is often misdiagnosed as a psychiatric disorder – the symptoms can present like depression or obsessive compulsive disorder.
Working alongside Derek Mitchell and Robert Bartha and using high-field imaging systems at Robarts, Finger used fMRI brain imaging to look specifically at a network in the brain called the limbic system, which is important for emotion and reward processing. These regions are normally activated during emotional expression; however, that activity is significantly reduced in patients with FTD.
“This kind of high-field imaging, found uniquely at Robarts, can show really subtle changes in brain function,” said Bartha. “The changes found in this study help us to understand how the disease is affecting the brain, and gives us new ideas about how and when to treat these patients.”
The hope is that boosting the activity in the limbic region in the brains of patients with FTD might lead to therapies to treat these deficits in emotional processing and empathy.
And Finger, Mitchell and Bartha think they may have the first step toward that goal. Their study showed that two potential therapies – one pharmacologic, and one behavioural intervention – actually ramped up the bold signal in this brain region in FTD patients. The pharmacologic therapy is a nasal oxytocin spray that floods the brain with this hormone associated with social behaviour.
The other therapy is a behavioural exercise where patients are asked to mimic facial expressions that they are shown on a screen while inside the MRI magnet.
Normally, when a person sees someone else who is sad, the observer – without realizing it – makes micro-movements that mimic that sad expression. In turn, the brain activates regions that would be activated as though that person were sad themselves – a phenomenon that is the cornerstone of empathy.
What the researchers found is that when they asked patients to mimic facial expressions, the brain imaging showed a change in this important region of the brain.
“It was really exciting for us because it was the first evidence that even in patients that have reasonably advanced neurodegeneration due to FTD, we could see that there still was some capacity in this region,” said Finger. “It raises the possibility that continuing the pharmacologic or behavioural intervention in a more sustained way might translate into improvement in their real-world emotional processing and their real-world empathy and emotional experience.”
The next step in their research is to test these two interventions for longer periods of time to see if it has an effect on the patient’s behaviour.
This work is just one illustration of the ways that clinician-scientists are working alongside researchers at Robarts to help answer real-world clinical questions. “When we talk about translational research, I think this study is a great example of that paradigm at work,” said Bartha. “Often at Robarts, a clinician who has a really interesting question based on a clinical problem will collaborate with a basic scientist such as myself and together we can develop methodology and techniques to answer these questions.”