BACKGROUND: Specific thalamic nuclei such as the Mediodorsal and the Pulvinar are known to play
a role in the pathophysiology of schizophrenia. However, the study of microstructural alterations that
take place in these nuclei in terms of gray versus white matter proportions, neurite density and organized
connectivity in the course of the disease has been limited due to the lack of specificity of standard
conventional imaging techniques.
METHODS: Twenty-three patients with a long-standing schizophrenia and thirty-five patients in the
early phase of psychosis as well as age and sex-matched healthy control subjects had their brain scanned
with T1-weighted Magnetic Resonance Imaging and Diffusion Spectrum Imaging. Each thalamus was
then divided into the various sub-nuclei using an atlas-based parcellation approach. Local microstructure
metrics were computed inside the Mediodorsal and Pulvinar nuclei using the recently developed Neurite
Orientation Dispersion and Density Imaging technique (NODDI).
RESULTS: Early-psychosis patients had significantly lower gray matter concentration in both sub-nuclei,
while chronic patients had more misaligned neurites in the Mediodorsal nucleus and an increased neurite
density in the right Pulvinar nucleus. Poor working memory performances in the early-psychosis cohort
were significantly correlated with increased neurite density in the Mediodorsal nucleus, whereas no
correlation was observed in the chronic group. In the Pulvinar nucleus correlations with psychotic positive
and negative symptoms were noted but they did not remain significant after multiple-testing correction.
CONCLUSION: The divergent results found in early-psychosis versus chronic patients may support
sequential pathological steps that take place in the course of the disease in specific thalamic nuclei. We
hypothesize that this sequence goes from a loss of gray matter to a progressive replacement by white
matter through an increased neurite density making up a disorganized network, suggesting a reduction of
complexity and efficiency of the trans-thalamic pathway in schizophrenia.