White matter microstructure predicts cognitive training-induced improvements in attention and executive functioning in schizophrenia

We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70h (~16weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70h of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.

[1]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[2]  M S Buchsbaum,et al.  MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia , 1998, Neuroreport.

[3]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[4]  M. Casanova,et al.  Functional and anatomical aspects of prefrontal pathology in schizophrenia. , 1997, Schizophrenia bulletin.

[5]  Susumu Mori,et al.  The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains , 2017, NeuroImage.

[6]  P. Bartolomeo,et al.  Attention and spatial cognition: Neural and anatomical substrates of visual neglect. , 2017, Annals of physical and rehabilitation medicine.

[7]  A. D. de Crespigny,et al.  Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. , 1999, Archives of general psychiatry.

[8]  D J Hawkes,et al.  An Information Theory Approach to the Alignment of Images Containing Measurement Inhomogeneity: Application to Mr Surface Coil Angiography of the Brain , .

[9]  G J Barker,et al.  In vivo investigation of white matter pathology in schizophrenia with magnetisation transfer imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[10]  R. Kikinis,et al.  Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study , 2003, Biological Psychiatry.

[11]  J C Gore,et al.  Preliminary evidence of improved verbal working memory performance and normalization of task-related frontal lobe activation in schizophrenia following cognitive exercises. , 2000, The American journal of psychiatry.

[12]  D. Bassett,et al.  Emerging Evidence of Connectomic Abnormalities in Schizophrenia , 2011, The Journal of Neuroscience.

[13]  M. Merzenich,et al.  Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. , 2006, Progress in brain research.

[14]  Michael F. Green,et al.  What are the functional consequences of neurocognitive deficits in schizophrenia? , 1996, The American journal of psychiatry.

[15]  A. MacDonald,et al.  Brain Correlates of Cognitive Remediation in Schizophrenia: Activation Likelihood Analysis Shows Preliminary Evidence of Neural Target Engagement. , 2015, Schizophrenia bulletin.

[16]  M. Catani,et al.  A diffusion tensor imaging tractography atlas for virtual in vivo dissections , 2008, Cortex.

[17]  M. Brammer,et al.  Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia. , 2002, The British journal of psychiatry : the journal of mental science.

[18]  R. Henry,et al.  Diffusion Tensor MR Imaging and Fiber Tractography: Theoretic Underpinnings , 2008, American Journal of Neuroradiology.

[19]  Walter Ritter,et al.  Associated deficits in mismatch negativity generation and tone matching in schizophrenia , 2000, Clinical Neurophysiology.

[20]  T. Klingberg.  Development of a superior frontal–intraparietal network for visuo-spatial working memory , 2006, Neuropsychologia.

[21]  Sophia Vinogradov,et al.  Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains , 2014, NeuroImage.

[22]  Theo G. M. van Erp,et al.  Diffusion Tensor Imaging of the Superior Longitudinal Fasciculus and Working Memory in Recent-Onset Schizophrenia , 2008, Biological Psychiatry.

[23]  B. Wexler,et al.  Successful computer-based visual training specifically predicts visual memory enhancement over verbal memory improvement in schizophrenia , 2011, Schizophrenia Research.

[24]  N. Costes,et al.  How can cognitive remediation therapy modulate brain activations in schizophrenia? An fMRI study , 2011, Psychiatry Research: Neuroimaging.

[25]  S. Vinogradov,et al.  Supplementing Intensive Targeted Computerized Cognitive Training With Social Cognitive Exercises for People With Schizophrenia: An Interim Report , 2017, Psychiatric rehabilitation journal.

[26]  P. McGuire,et al.  White matter deficits in schizophrenia are global and don’t progress with age , 2017, The Australian and New Zealand journal of psychiatry.

[27]  Carl-Fredrik Westin,et al.  DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity , 2005, NeuroImage.

[28]  Manzar Ashtari,et al.  Reduced frontal white matter integrity in Early-Onset schizophrenia: a preliminary study , 2004, Biological Psychiatry.

[29]  M. Witter,et al.  Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions , 2003, Neuropsychologia.

[30]  Stephen M. Smith,et al.  Crossing fibres in tract-based spatial statistics , 2010, NeuroImage.

[31]  A. Meyer-Lindenberg,et al.  Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia , 2012, Neuropsychopharmacology.

[32]  N C Andreasen,et al.  Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Julia P. Owen,et al.  Abnormal white matter microstructure in children with sensory processing disorders☆ , 2013, NeuroImage: Clinical.

[34]  Alex Fornito,et al.  Abnormal white matter microstructure in schizophrenia: A voxelwise analysis of axial and radial diffusivity , 2008, Schizophrenia Research.

[35]  Michael B. First,et al.  The DSM Series and Experience with DSM-IV , 2002, Psychopathology.

[36]  Michael F. Green,et al.  A novel, online social cognitive training program for young adults with schizophrenia: A pilot study , 2014, Schizophrenia Research: Cognition.

[37]  G. Vingerhoets,et al.  Brain Connectomics of Visual-Motor Deficits in Children with Developmental Coordination Disorder. , 2016, The Journal of pediatrics.

[38]  D. Javitt.  When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. , 2009, Annual review of clinical psychology.

[39]  G. Pergola,et al.  The role of the thalamus in schizophrenia from a neuroimaging perspective , 2015, Neuroscience & Biobehavioral Reviews.

[40]  Karl J. Friston.  The disconnection hypothesis , 1998, Schizophrenia Research.

[41]  G. Rizzolatti,et al.  The organization of the cortical motor system: new concepts. , 1998, Electroencephalography and clinical neurophysiology.

[42]  T. Kinoshita,et al.  Diffusion Tensor Magnetic Resonance Imaging of Disruption of Regional White Matter in Schizophrenia , 2003, Neuropsychobiology.

[43]  P Bartolomeo,et al.  Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[44]  Michael Sanfilipo,et al.  Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study. , 2003, The American journal of psychiatry.

[45]  Feliberto de la Cruz,et al.  Structural and functional dysconnectivity of the fronto-thalamic system in schizophrenia: A DCM-DTI study , 2015, Cortex.

[46]  R. Kikinis,et al.  Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. , 2002, The American journal of psychiatry.

[47]  Philip D. Harvey,et al.  White matter changes in schizophrenia: evidence for myelin-related dysfunction. , 2003, Archives of general psychiatry.

[48]  G. V. Simpson,et al.  When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia. , 2009, Schizophrenia bulletin.

[49]  Alan Connelly,et al.  Track density imaging (TDI): Validation of super resolution property , 2011, NeuroImage.

[50]  P. Skudlarski,et al.  Brain Connectivity Is Not Only Lower but Different in Schizophrenia: A Combined Anatomical and Functional Approach , 2010, Biological Psychiatry.

[51]  P. Hof,et al.  Oligodendrocyte pathophysiology: a new view of schizophrenia. , 2007, The international journal of neuropsychopharmacology.

[52]  J. Bogousslavsky,et al.  The thalamus and behavior , 2006, Neurology.

[53]  Derek K. Jones,et al.  Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia , 2006, Human brain mapping.

[54]  Alan Connelly,et al.  Track-density imaging (TDI): Super-resolution white matter imaging using whole-brain track-density mapping , 2010, NeuroImage.

[55]  Sophia Vinogradov,et al.  Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. , 2009, The American journal of psychiatry.

[56]  Julia P. Owen,et al.  Edge density imaging: Mapping the anatomic embedding of the structural connectome within the white matter of the human brain , 2015, NeuroImage.

[57]  Kristen M. Haut,et al.  Prefrontal Cortical Changes Following Cognitive Training in Patients with Chronic Schizophrenia: Effects of Practice, Generalization, and Specificity , 2010, Neuropsychopharmacology.

[58]  E. Bullmore,et al.  Meta-analysis of diffusion tensor imaging studies in schizophrenia , 2009, Schizophrenia Research.

[59]  M. Merzenich,et al.  Principles of neuroplasticity-based rehabilitation. , 2013, Progress in brain research.

[60]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

[61]  Gregory V. Simpson,et al.  Computerized Cognitive Training Restores Neural Activity within the Reality Monitoring Network in Schizophrenia , 2012, Neuron.

[62]  G. Rizzolatti,et al.  The Organization of the Frontal Motor Cortex. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[63]  John G. Csernansky,et al.  Anterior thalamic radiation integrity in schizophrenia: A diffusion-tensor imaging study , 2010, Psychiatry Research: Neuroimaging.

[64]  W H Wong,et al.  Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Michael F. Green,et al.  The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. , 2008, The American journal of psychiatry.

[66]  A. MacDonald,et al.  Increases in Intrinsic Thalamocortical Connectivity and Overall Cognition Following Cognitive Remediation in Chronic Schizophrenia. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.