Social cognition (SC) is a fundamental neurocognitive capability that refers to the perception, processing, and interpretation of social information (Henry et al., 2016). SC is also critical for the understanding of oneself and others, as well as of societal norms and procedures. Disturbances of SC can exist in many neuropsychiatric or chronic neurological disorders; more over, they also can happen in patients with stroke (Henry et al., 2016). Impairments in SC have been correlated with poorer outcomes, including quality of life, mental health problems, unemployment, and loneliness (Phillips et al., 2010). Even in stroke patients with good physical recovery, SC impairments may hinder reintegration to everyday life (Qu et al., 2022a,b).

Adams et al. (2019) reported that SC deficit in stroke can be identified in four core domains: theory of mind, social perception, affective empathy, and social behavior. Social behavior refers to how a person performs during interactions with other people (Santamaría-García et al., 2022). Besides with social behavior, long-term impairments in SC are even present in mildly affected stroke patients; and these impairments may perplex such patients permanently (Nijsse et al., 2019).

The exact pathophysiological mechanism of SC impairment has not been identified. Gunaydin et al. (2014) demonstrated that the optogenetic control of cells that specifically contribute to projections from the ventral tegmental area to the nucleus accumbens modulate the social behavior. In an animal experiment, the researchers found that in mice with striatal cholinergic interneurons ablation, the normal pattern of social exploration was replayed continuously and, arising compulsive social behavior (Yanina et al., 2017). These specific neurons often form specific structure or circuit. Chaudhury et al. (2013) reported that, in the ventral tegmental area, dopamine neurons in the brain’s reward circuit have a crucial role in mediating stress responses, including determining susceptibility versus resilience to social-stress-induced behavioral abnormalities. Kana et al. (2021) found in patients with Alzheimer’s dementia that the medial septum/vertical diagonal band of Broca and nucleus basalis magnocellularis cholinergic neurons play distinct roles in social interaction and social recognition memory (Kana et al., 2021). As the intact SC related to different scope of neural structure, from neurotransmitter to structural brain abnormalities, involve in the extensive white matter may contribute to changes in SC (Wang and Olson, 2018).

Several factors might contribute to the disturbance of social behavior after stroke. A previous study revealed that the severity of SC impairments is determined mainly by demographic factors (Adams et al., 2020). However, the putative risk factors of social behavioral changes in patients with stroke are not well understood, especially in relation to neuroimaging features. Hence, the present study tried to explore the clinical and neuroimaging factors which may correlate with changes in social behavior in patients with ischemic stroke.

During the study period, we had totally screened 515 patients with first-ever acute ischemic stroke. Finally, 80 patients were included in the analysis according to selection criteria (Figure 1).

The study population consisted of 51 (63.8%) men and 29 (36.2%) women (Table 1). The mean age was 60.53 ± 9.51 years and the NIHSS score on discharge was 1 (0–2).

The results of other SC on follow-up were as follows (mean [range]): empathy, 37.5 (30.5–48); facial expression right recognition, 37 (29.5–45); facial expression remote wrong recognition, 50 (40–65). There were no significant correlations between neither deficit or positive behavioral changes and the above other aspects of social cognition.

We conducted a protocol of multimodal MRI and assessed changes in the social behavior of patients on 3 months post-stroke. The volumes of various subcortical, ventricular structures and WMH using the three-dimensional T1-weighted images were calculated by an automatic tool. Our main findings were that larger DWMH volumes and poorer mRS scores on follow-up were significantly correlated with more severe deficit behavioral changes in patients with subacute ischemic stroke (Figure 2).

White matter connectivity is essential for organized human behavior. Working together with gray matter to enable the large repertoire of human cognitive capacities (Filley and Fields, 2016). WMH can be found in stroke; and relate to many complications, such as decreased cortical thickness (Dickie et al., 2020), cognitive decline/ dementia (Tziaka et al., 2023), stroke-related mood disorders/depression (Kim et al., 2011; Zhang et al., 2023), physical recovery (Dai et al., 2022), and even functional status (Qu et al., 2022a,b). According to histopathologic research by Fazekas et al. (1993) WMH are usually distributed between PVH and confluent DWMH, and can be measured using a semiquantitative method known as the Fazekas grade scale. Benefit from the advanced neuroimaging analysis techniques, we now can precisely quantify the volumes of either PVH or DWMH, leading to more comprehensive insight to the relationship between WMH and stroke. Similar to a previous study (Kim et al., 2022), the median DWMH volume was 0.82 (0.369–1.46) ml in the presented study. Furthermore, our main finding was that larger DWMH volumes were significantly correlated with greater FBI deficit behavior scores. This finding suggests that more severe changes in deficit social behaviors are associated with larger DWMH volumes in subacute ischemic stroke. A relationship between WMH and SC impairment has also been observed in other studies. For example, a previous study investigating the contribution of WMH and cortical thickness to empathy found that cortical atrophy and WMH volume may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases (Ozzoude et al., 2022). Moreover, Yang et al. (2022) reported that a higher WMH load is correlated with mild behavioral impairment in patients with normal cognitive function. The latent causality between WMH and SC impairment may be explained by pathological changes that are highlighted by modal magnetic resonance techniques. The extension of hyperintensities alongside the lateral ventricles, as a small rim or even a halo of PVH, appears to be associated with both a thin rim of subependymal gliosis and a wider, smooth band of white matter tissue, with reduced staining for myelin around the lateral ventricles (Fazekas et al., 1998).

The presented study tried to investigated the relationship between the changes in the social behavior and the infarcts (Figure 3), cortical / subcortical structures, cholinergic pathways and white matter. The left cortical infarct was although related to deficit behavioral changes in the univariate analysis, but it was not significant correlation after adjusted for the confounders. And it found that the social behavior was not correlated to involvement of neither the cortical/subcortical structures or cortical cholinergic pathways, except for white matter lesions. The intact SC require a collection of large-scale networks in diverse brain regions. The operation and coordination of such highly distributed brain areas would be impossible without the presence of extensive white matter tracts for the long-range transmission of communication; this neuroanatomical infrastructure might be more crucial for SC than for other cognitive functions that are underpinned by a single structure or a small set of anatomically clustered brain structures (Wang and Olson, 2018).

In the present study, poorer physical status was also correlated with more severe social behavior changes in the subacute phase of ischemic stroke. Clinical factors other than the severity of stroke (as assessed by the NIHSS) may determine the severity of social impairments in stroke patients. Poorer physical function is significantly correlated with reduced abilities of daily living, which may induce multiple dysfunctions such as memory and executive dysfunctions (McDonald et al., 2019). Because our study mainly included stroke patients with mild residual disabilities, it was a relatively homogeneous sample for studying social behavioral changes in ischemic stroke (Nijsse et al., 2019).

Our study had the following strengths. First, it was a longitudinal and prospective study. Second, we assessed social behavior in patients with mild stroke, who were with mild impairments in motor, cognitive and activities of daily living functioning, logically revealed changes in social behavior after ischemic stroke. Third, we used the advanced neuroimaging analysis techniques on the basis of a multimodal MRI protocol. There were also some limitations in this study. First, the sample size was relatively small. Second, we did not investigated the general cognition on the follow-up. Third, although we had excluded severe aphasia according to NIHSS score, in consideration of language impairments have devastating effects on the behavior and mood of affected individuals (Edelkraut et al., 2022), however, we did not specially assess the relationship of the brain damage that occurred in language-dominant left hemisphere and the negative symptoms of behavioral changes. This need to be improved in the further study.

In conclusion, we found that larger DWMH volume and poorer mRS on follow-up were significantly correlated with deficit behavioral changes in subacute ischemic stroke.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

The studies involving humans were approved by Ethics Committee of the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

J-FQ: Data curation, Formal analysis, Investigation, Visualization, Writing – original draft. H-HH: Data curation, Formal analysis, Investigation, Resources, Writing – review & editing. J-FL: Formal analysis, Investigation, Methodology, Resources, Writing – review & editing. Y-QZ: Methodology, Resources, Software, Validation, Writing – review & editing. W-YC: Data curation, Formal analysis, Investigation, Resources, Writing – review & editing. LS: Investigation, Methodology, Resources, Validation, Writing – review & editing. LZ: Formal analysis, Investigation, Supervision, Visualization, Writing – review & editing. YK-C: Conceptualization, Supervision, Validation, Visualization Writing – review & editing. Y-SL: formal-analysis, investigation, resources, supervision, writing-review-editing.