Striato-nigro-striatal tract dispersion abnormalities in patients with chronic schizophrenia
The white matter connections between the midbrain dopamine neurons and the striatum are part of a neural system involved in reward-based learning, a process that is impaired in patients with schizophrenia. The striato-nigro-striatal (SNS) tract, which participates in this process, has not as yet been explored. The present study aimed to use diffusion MRI (dMRI) to delineate the SNS tract, and to compare the application of two dMRI measures, Tract Dispersion (TD), an index of white matter morphology, and Fractional Anisotropy (FA), an index of white matter integrity, to detect group differences between patients with chronic schizophrenia (CSZ) and healthy controls (HC). dMRI scans were acquired in 22 male patients with CSZ and 23 age-matched HC. Two-tensor tractography was used in addition to manually-delineated regions of interest to extract the SNS tract. A mixed-model analysis of variance was used to investigate differences in TD and FA between CSZ patients and HC. The associations between TD and behavioral measures were also explored. Patients and controls differed significantly in TD (P = 0.04), but not in FA (P = 0.69). The group differences in TD were driven by a higher TD in the right hemisphere in the CSZ group. Higher TD correlated significantly with poorer performance in the Iowa Gambling Task (IGT) when combining the scores of both groups. The findings suggest that dysconnectiviy of the SNS tract which is associated with schizophrenia, could arise from abnormalities in white matter morphology. These abnormalities may potentially reflect irregularities in brain development.
KeywordsDiffusion MRI Reward processing Psychotic symptoms
This study was supported by The National Institutes of Health (P50MH080272 (RWM (Program Director) MK, PGN, MN, MES), R01AG04252 (MK), R01MH102377 (MK)), the Veterans Affairs Merits Awards (JJL, RWM) (I01CX000176 (MES), and a NARSAD Young Investigator Award (22591 (PS)).
Compliance with ethical standards
Conflict of interest
Ana Maria Rivas-Grajales, Peter Savadjiev, Marek Kubicki, Paul G. Nestor, Margaret Niznikiewicz, Robert W. McCarley, Carl-Fredrik Westin, Martha E. Shenton and James J. Levitt declare that they have no conflicts of interest.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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