Thalamic Nuclei Connectivity in the Psychosis Continuum: Parsing Clinical Heterogeneity and Individual Trajectories

Objetivo

Psychotic disorders are among the top causes of global disability due to their early onset and poor clinical outcomes. Forty percent of patients show no improvement within the first year despite access to evidence-based treatments. Yet, clinical trajectories after psychosis onset remain highly heterogeneous and poorly understood. Structural and functional thalamocortical dysconnectivity is consistently observed in early-stage psychosis (EP), contributing to persistent symptoms and impaired functional recovery. Research has largely focused on single-modality connectivity features of the thalamus as a whole, neglecting the anatomical specificity of its nuclei in shaping structure-function brain networks and symptom domains. THALAMIND aims to identify clinically relevant nuclei-specific thalamocortical structure-function connectivity coupling (SFCC) along the psychosis continuum (subclinical/schizotypy, EP, chronic). Leveraging multimodal magnetic resonance imaging, THALAMIND will examine how deviations of functional brain signals from the underlying anatomical architecture inform symptom severity, functional impairment, and short- and long-term outcomes. Traditional approaches have primarily focused on static models of SFCC, failing to capture transient dynamic fluctuations in thalamocortical connectivity. This proposal integrates both static and dynamic graph-based connectivity measures to assess spatially and spectrally specific thalamocortical SFCC profiles underlying clinical heterogeneity. Using this state-of-the-art multimodal approach, the proposed research will determine whether altered signal propagation in specific thalamic circuits can inform psychosis physiopathology and outcome prediction in EP. By characterizing clinically relevant thalamocortical SFCC patterns, THALAMIND will enable neurobiologically informed patient stratification to develop personalized early treatment strategies, with the goal of improving functional recovery and reducing disability.