Is living on the coast associated with midlife multimorbidity in England and Wales? A cross-birth cohort analysis of the relationship between long-term residence and selective migration.

Functional neurological disorder (FND) is a common, costly, and potentially disabling condition at the neurology-psychiatry intersection, characterized by motor, sensory, and cognitive symptoms. Mixed symptoms occur in one-quarter to one-half of individuals, with others developing distinct functional neurological symptoms longitudinally. The most well-studied FND phenotypes are the motor (FND-motor) and seizure (FND-seizure) variants, frequently co-occurring with affective and trauma-related conditions. The biopsychosocial complexity of FND underscores the importance of multidisciplinary care, with clinical trials and naturalistic cohort studies supporting roles for psychotherapy and physical rehabilitation. Nonetheless, there is individual-level heterogeneity regarding clinical trajectories. As such, there is a need to investigate how brain network organization relates to FND symptom change over time. Resting-state functional connectivity (rsFC) alterations in somatomotor (SMN), ventral attention (VAN)/salience, and default mode (DMN) networks, among others, have been identified across FND cohort studies. Several studies found aberrant connectivity between the VAN/salience network and motor control regions, and between the temporoparietal junction (TPJ) and sensorimotor regions. Work from our group identified altered functional network architecture in FND, marked by increased cortical integration (- connectivity) for SMN regions, with heightened connections to the VAN, DMN, and frontoparietal (FPN) networks. These findings support the hypothesis that distributed, network-level disruptions play a role in the pathophysiology of FND, with potential relevance as baseline predictors of clinical trajectories and as mechanisms underlying longitudinal symptom change. Research has begun to explore neuroimaging correlates of clinical trajectories in FND. For example, improvements in functional tremor following cognitive behavioural therapy (CBT) were linked to decreased anterior cingulate and paracingulate activations. Following 1 week of multidisciplinary treatment, increased amygdala-ventromedial prefrontal cortex functional connectivity was observed in the subset of FND-motor patients with a favourable response. Improved outcomes in a mixed FND cohort have been associated with greater supplementary motor area signal variability, whereas worse outcomes were associated with higher baseline left insula variability. In earlier FND research, we identified an association between improved symptom scores and relative baseline increases in left centromedial amygdala-to-right anterior insula rsFC. Nonetheless, much of the literature has relied on region-of-interest (ROI) approaches, examined either baseline predictors or post-treatment mechanisms in isolation, or focused on narrowly defined subpopulations (e.g. euthymic individuals only). This underscores the need for longitudinal, whole-brain investigations that examine both predictors and mechanisms of symptom change in a representative FND cohort.