Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders

Biol Psychiatry. 2016 Jun 15;79(12):1016-25. doi: 10.1016/j.biopsych.2015.06.026. Epub 2015 Jul 2.


Background: There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis.

Methods: Resting-state functional magnetic resonance imaging was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early-stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions of interest (ROIs) on the basis of connectivity with six a priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxelwise seed-based analyses to further localize thalamic dysconnectivity.

Results: ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early-stage psychosis patients. PFC hypoconnectivity and motor cortex hyperconnectivity correlated in patients, suggesting that they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypoconnectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described executive control network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory.

Conclusions: Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment.

Keywords: Chronic; Cortex; Early stage; Psychosis; Resting-state fMRI; Thalamus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Affective Disorders, Psychotic / complications
  • Affective Disorders, Psychotic / diagnostic imaging
  • Affective Disorders, Psychotic / physiopathology*
  • Cerebellum / diagnostic imaging
  • Cerebellum / physiopathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology*
  • Connectome / methods*
  • Executive Function / physiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Motor Cortex / diagnostic imaging
  • Motor Cortex / physiopathology
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Psychotic Disorders / complications
  • Psychotic Disorders / diagnostic imaging
  • Psychotic Disorders / physiopathology*
  • Schizophrenia / complications
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / physiopathology*
  • Thalamus / physiopathology*
  • Young Adult