PMID- 29667043 OWN - NLM STAT- MEDLINE DCOM- 20190812 LR - 20200401 IS - 1931-7565 (Electronic) IS - 1931-7557 (Print) IS - 1931-7557 (Linking) VI - 13 IP - 2 DP - 2019 Apr TI - Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia: a two-tensor tractography study. PG - 472-481 LID - 10.1007/s11682-018-9862-8 [doi] AB - The "cognitive dysmetria" hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder. FAU - Hamoda, Hesham M AU - Hamoda HM AD - Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA, USA. hesham.hamoda@childrens.harvard.edu. AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hesham.hamoda@childrens.harvard.edu. FAU - Makhlouf, A T AU - Makhlouf AT AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. FAU - Fitzsimmons, J AU - Fitzsimmons J AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Rathi, Y AU - Rathi Y AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Makris, N AU - Makris N AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Mesholam-Gately, R I AU - Mesholam-Gately RI AD - Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. FAU - Wojcik, J D AU - Wojcik JD AD - Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. FAU - Goldstein, J AU - Goldstein J AD - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Division of Women's Health, Connors Center for Women's Health & Gender Biology; Departments of Psychiatry and Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - McCarley, R W AU - McCarley RW AD - Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA, USA. FAU - Seidman, L J AU - Seidman LJ AD - Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. FAU - Kubicki, M AU - Kubicki M AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Shenton, M E AU - Shenton ME AD - Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. AD - Veterans Affairs Boston Healthcare System, Brockton Division, Brockton, MA, USA. LA - eng GR - R01 MH102377/MH/NIMH NIH HHS/United States GR - P50 MH080272/MH/NIMH NIH HHS/United States GR - R01MH097979/National Institute of Mental Health/ GR - R01 MH097979/MH/NIMH NIH HHS/United States GR - R01MH102377/National Institute of Mental Health/ GR - NIH P50MH080272/National Institute of Mental Health/ GR - T32 MH016259/MH/NIMH NIH HHS/United States GR - R01MH050740/National Institute of Mental Health/ GR - SCDMH82101008006/Commonwealth Research Center/ PT - Journal Article PL - United States TA - Brain Imaging Behav JT - Brain imaging and behavior JID - 101300405 MH - Adult MH - Anisotropy MH - Brain/pathology MH - Cross-Sectional Studies MH - Diffusion Tensor Imaging/*methods MH - Female MH - Gyrus Cinguli/pathology MH - Humans MH - *Image Processing, Computer-Assisted MH - Male MH - Prefrontal Cortex/pathology MH - Schizophrenia/*pathology MH - Thalamus/*pathology MH - White Matter/*pathology MH - Young Adult PMC - PMC6192863 MID - NIHMS960485 OTO - NOTNLM OT - MRI OT - Schizophrenia OT - Thalamus OT - Tractography EDAT- 2018/04/19 06:00 MHDA- 2019/08/14 06:00 PMCR- 2020/04/01 CRDT- 2018/04/19 06:00 PHST- 2018/04/19 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2018/04/19 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - 10.1007/s11682-018-9862-8 [pii] AID - 10.1007/s11682-018-9862-8 [doi] PST - ppublish SO - Brain Imaging Behav. 2019 Apr;13(2):472-481. doi: 10.1007/s11682-018-9862-8.