Anne L Wheeler1, M Mallar Chakravarty2, Jason P Lerch3, Jon Pipitone2, Zafiris J Daskalakis4, Tarek K Rajji5, Benoit H Mulsant6, Aristotle N Voineskos7. 1. Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 2. Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; 3. Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; 4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; 5. Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 6. Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; 7. Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; aristotle.voineskos@camh.ca.
Abstract
BACKGROUND: Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder. METHODS: T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18-55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored. RESULTS: Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance. CONCLUSIONS: We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia.
BACKGROUND: Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder. METHODS: T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18-55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored. RESULTS: Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance. CONCLUSIONS: We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia.
Authors: Aristotle N Voineskos; Nancy J Lobaugh; Sylvain Bouix; Tarek K Rajji; Dielle Miranda; James L Kennedy; Benoit H Mulsant; Bruce G Pollock; Martha E Shenton Journal: Brain Date: 2010-03-17 Impact factor: 13.501
Authors: Mera S Barr; Faranak Farzan; Tarek K Rajji; Aristotle N Voineskos; Daniel M Blumberger; Tamara Arenovich; Paul B Fitzgerald; Zafiris J Daskalakis Journal: Biol Psychiatry Date: 2012-10-03 Impact factor: 13.382
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Authors: Alyson M Rich; Youngsun T Cho; Yanqing Tang; Aleksandar Savic; John H Krystal; Fei Wang; Ke Xu; Alan Anticevic Journal: Psychiatry Res Neuroimaging Date: 2016-02-12 Impact factor: 2.376
Authors: Luanna Dixson; Henrik Walter; Michael Schneider; Susanne Erk; Axel Schäfer; Leila Haddad; Oliver Grimm; Manuel Mattheisen; Markus M Nöthen; Sven Cichon; Stephanie H Witt; Marcella Rietschel; Sebastian Mohnke; Nina Seiferth; Andreas Heinz; Heike Tost; Andreas Meyer-Lindenberg Journal: Proc Natl Acad Sci U S A Date: 2014-06-16 Impact factor: 11.205