The neural substrates of social cognition deficits in newly diagnosed multiple sclerosis patients

Abstract

Objective: Cognitive and affective symptoms in multiple sclerosis (MS) can be independently impaired and have different pathways of progression. Cognitive alterations have been described since the earliest MS stages; by contrast, the social cognition (SC) domain has never been investigated in the first year from MS diagnosis. We aimed to evaluate SC and unravel its neural bases in newly diagnosed MS patients.

Methods: Seventy MS patients underwent at diagnosis a 3 T-MRI and a neuropsychological/SC assessment (median time between diagnosis and MRI/cognitive evaluation = 0 months). We tested two matched reference samples: 31 relapsing-remitting MS patients with longer course (mean ± SD disease duration = 7.0 ± 4.5 years) and 38 healthy controls (HCs). Cortical thicknesses (CTh) and volumes of brain regions were calculated.

Results: Newly diagnosed MS patients performed significantly lower than HCs in facial emotion recognition (global: p < 0.001; happiness: p = 0.041, anger: p = 0.007; fear: p < 0.001; disgust: p = 0.004) and theory of mind (p = 0.005), while no difference was found between newly diagnosed and longer MS patients. Compared to lower performers, higher performers in facial emotion recognition showed greater volume of amygdala (p = 0.032) and caudate (p = 0.036); higher performers in theory of mind showed greater CTh in lingual gyrus (p = 0.006), cuneus (p = 0.024), isthmus cingulate (p = 0.038), greater volumes of putamen (p = 0.016), pallidum (p = 0.029), and amygdala (p = 0.032); patients with higher empathy showed lower cuneus CTh (p = 0.042) and putamen volume (p = 0.007).

Interpretations: SC deficits are present in MS patients since the time of diagnosis and remain persistent along the disease course. Specific basal, limbic, and occipital areas play a significant role in the pathogenesis of these alterations.

Figure 1

Global performance in the three social cognition domains among the three groups evaluated: the experimental groups (MS patients at diagnosis, red‐colored) and the two reference groups (healthy controls, green‐colored, and MS patients with a longer course of disease, blue‐colored). Highlighted the results of the statistical comparisons between the experimental group and the two control groups. **p < 0.01; ***p < 0.001.

Figure 2

Significant differences in terms of MRI results between MS patients lower and higher performers in the facial emotion recognition task. *p < 0.05.

Figure 3

Significant differences in terms of MRI results between MS patients lower and higher performers in the theory of mind task. *p < 0.05; **p < 0.01.

Figure 4

Significant differences in terms of MRI results between MS patients lower and higher performers in the empathy questionnaire. *p < 0.05; **p < 0.01.

Figure 5

Brain representations showing regions of interest that showed a significant association with the three domains of social cognition: facial emotion recognition (TOFER‐KF test, red‐colored); theory of mind (RME test, blue‐colored); empathy (EQ questionnaire, green‐colored).