A study from Karolinska Institute investigated empathy loss in behavioral variant frontotemporal dementia (bvFTD) using functional magnetic resonance imaging (fMRI) to analyze brain responses during pain empathy tasks. In 28 patients with bvFTD and 28 controls, researchers observed significant reductions in brain activity in regions associated with affective empathy, but not cognitive empathy.
Behavioral variant frontotemporal dementia (bvFTD) is a condition characterized by significant changes in behavior and personality, with loss of empathy being a central symptom.
Empathy, especially the affective aspect, appears to be impaired independently of other cognitive or socio-emotional functions in these patients.
This study, published by researchers from Karolinska Institute, aimed to investigate how brain responses during pain empathy (PFE) tasks are altered in individuals with bvFTD.
To do this, an already established functional magnetic resonance imaging (fMRI) paradigm was used. This technique allows us to observe how different areas of the brain respond to specific stimuli, offering insights into neural functioning related to empathy.
The researchers recruited 28 individuals diagnosed with bvFTD and 28 cognitively normal participants to form the control group. The diagnosis of bvFTD followed accepted international criteria, and the individuals were assessed using the Interpersonal Reactivity Index (IRI), a tool that measures different dimensions of empathy.
The study was conducted in accordance with international and local ethical guidelines, with written informed consent obtained from all participants.
During the experiments, the participants performed specific tasks involving empathy for pain, while their brain activity was monitored by fMRI. The paradigm included a control condition and a pain condition. The difference in neural response between these conditions was analyzed using the blood oxygen level dependent (BOLD) signal, which indicates brain activity.
To identify differences between the groups, the researchers used appropriate statistical tests. In the case of normally distributed variables, Student's t-tests were applied. For variables with different distributions, Mann-Whitney U tests were used. A P value of less than 0.05 was considered statistically significant.
Two main approaches were used to analyze specific brain areas:
One was based on previous meta-analyses, which identified areas that were generally activated during pain empathy tasks.
The other was based on the pattern of activation observed in controls during the experiment, known as CA-ROI.
The latter approach was used to explore associations between neural activity and the results of the IRI, which reflects the empathic capacity of each individual.
The results showed that controls showed greater activation in 12 brain areas related to pain empathy, while patients with bvFTD showed activation in only 2 areas.
Experimental fMRI paradigm and BOLD signal change in the pain empathy contrast. The figure shows an example of 20 images of a cotton swab touching a hand (A) and 1 example of 20 images of a needle piercing a hand (B) displayed during the functional magnetic resonance imaging (fMRI) experiment. A fixation cross is displayed for 3–5 s, followed by the text “What is the hand feeling?” displayed for 3 s. Subsequently, the image is displayed for 3.5 s, after which a black image is displayed for 4.5 s before a new cycle is initiated with a new fixation cross. Areas with significant increase in blood oxygen level-dependent (BOLD) signal in control participants (C) and in patients with behavioral variant frontotemporal dementia (D) in the pain empathy contrast. The colored bar displays z-scores (red z > 3.1, yellow z = 4.5).
Furthermore, a reduction in BOLD signal was particularly notable in the ROI associated with affective empathy (control: mean increase of 20.86%; bvFTD: mean decrease of -1.26%). Interestingly, cognitive empathy showed no significant changes.
Furthermore, in controls, brain activity in the regions of interest was positively correlated with self-rated empathy on the IRI, while in patients, it was correlated with ratings made by family members.
The results indicate that individuals with bvFTD have reduced neural activity in brain areas that are key to empathy processing.
These regions are known to be affected early in bvFTD, which reinforces the importance of investigating the role of the brain in complex social functions. The study also showed that the level of empathy, as rated by family members, was related to the magnitude of neural activity observed.
Although the results are significant, the study has some limitations. Different MRI scanners were used, which may introduce variability. The sample included both genetic and sporadic cases of bvFTD, which may influence the findings. There was no neuropathological confirmation of the diagnoses, which reduces the absolute accuracy in classifying patients.
These limitations were addressed in sensitivity analyses, but should still be considered when interpreting the results.
This study provides important evidence that empathy, particularly its affective component, is impaired in patients with bvFTD. fMRI has proven to be a powerful tool for exploring these brain alterations and relating them to symptoms observed in patients’ daily lives.
Furthermore, the findings highlight the relevance of diagnostic approaches that integrate neuroimaging and behavioral assessments.
READ MORE:
Altered Empathy Processing in Frontotemporal Dementia
Olof Lindberg, Tie-Qiang Li, Cecilia Lind, Susanna Vestberg, Ove Almkvist, Mikael Stiernstedt, Anita Ericson, Nenad Bogdanovic, Oskar Hansson, Luke Harper, Eric Westman,Caroline Graff, Theofanis Tsevis, Peter Mannfolk, Håkan Fischer, Gustav Nilsonne, Predrag Petrovic, Lars Nyberg, Lars-Olof Wahlund, and Alexander F. Santillo
JAMA Netw Open. 2024;7(12):e2448601.
doi:10.1001/jamanetworkopen.2024.48601
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