Psychosis is a debilitating trans-diagnostic syndrome characterized by hallucinations and delusions (Rehm and Shield 2019). The thalamus and its cortical connections play a crucial role in the pathophysiology of psychosis (Onofrj et al. 2023; Moustafa et al. 2017). However, despite often referred to as one structure, the thalamus is composed of separate nuclei with distinct cortical connections (Sherman and Guillery 2006). Recent investigations revealed lower volumes of only the medial thalamic subnuclei in first-episode psychosis patients (Thalhammer et al., 2023, in revision). Correspondingly, the current study hypothesizes selectively aberrant medial thalamus-cortex connections in adults with early psychosis.We investigated thalamo-cortical structural connectivity in 52 controls and 77 subjects with psychosis from the Human Connectome Project for Early Psychosis (https://www.humanconnectome.org/study/human-connectome-project-for-early-psychosis). Cortical regions and thalamic subnuclei were segmented using FreeSurfer. Diffusion-weighted images were preprocessed using FSL to derive fractional anisotropy measures (FA). Probabilistic tractography between thalamus and cortex was performed to derive connection probability and connection density measures. Group differences in thalamic microstructure and thalamocortical projections were investigated using ANCOVA with Tukey’s post-hoc test.We found lower connection probability (F(1,111)=4.23, p=0.04) and lower connection density (F(1,111)=4.10, p=0.05) specifically in tracts between the medial thalamus and the frontal cortex in psychosis. The microstructure of all thalamic subnuclei examined with FA was not altered in psychosis. Aberrant connection markers were not linked with psychosis symptoms.Results demonstrate selectively aberrant thalamo-cortical connectivity for medial thalamus nuclei and frontal cortices in early psychosis. Data support the prominent role of medial thalamus in psychosis spectrum disorders.