Neural circuits that affect social functioning in dementia

The dependency that humans have on each other for survival creates a great need to correctly process social information and likely drove our brains to be highly specialized towards social functioning. These processes are however affected in some types of dementia. The earliest clinical presentation seen in patients with behavioral variant frontotemporal dementia (bvFTD) are a diminished response to other people’s needs, decreased interpersonal warmth, impairment in socially appropriate behavior and lack of empathy. These symptoms significantly burden their caregivers and are likely linked to disrupted connectivity within intrinsic brain networks. This thesis explores how network integrity influences social behavior, with a focus on the salience network (SN) and the semantic appraisal network (SAN).

Our findings show that the SN plays a central role in interpreting others' intentions, surpassing the role of other brain circuits. Using dynamic causal modeling, we also found that sensitivity to social cues depends heavily on the SN’s output from the periaqueductal gray to right hemisphere structures. In bvFTD, this directional connectivity seems disrupted, and any remaining sensitivity appears driven by left-sided pathways. This suggests that the SN, and the direction of information flow among SN nodes, is vital for decoding socially relevant information. The SAN was shown to support understanding of social concepts, with structural integrity of regions like the subgenual ACC and anterior temporal lobes predicting performance on the newly developed Social Interaction Vocabulary Test, which distinguished social semantic processing from general semantic knowledge. Since this social semantic processing task was not yet available in a non-English format, we made a translation of this task and tested the psychometric validity, which was sufficient.

Together, these results highlight how damage to specific nodes in the SN and SAN undermines the ability to detect and evaluate social signals and contribute to the unique social deficits observed in some types of dementia. This information can support more accurate diagnosis and identification of targets for intervention, and it offers insight to caregivers to better comprehend and cope with dementia that affects their loved ones’ social functioning.