White Matter Damage Impairs Access to Consciousness in Multiple Sclerosis

a r t i c l e i n f o Global neuronal workspace theory predicts that damage to long-distance white matter (WM) tracts should impair access to consciousness during the perception of brief stimuli. To address this issue, we studied visual backward masking in 18 patients at the very first clinical stage of multiple sclerosis (MS), a neurological disease characterized by extensive WM damage, and in 18 matched healthy subjects. In our masking paradigm, the visibility of a digit stimulus increases non-linearly as a function of the interval duration between this target and a subsequent mask. In order to characterize quantitatively, for each subject, the transition between non-conscious and conscious perception of the stimulus, we used non-linear regression to fit a sigmoid curve to objective performance and subjective visibility reports as a function of target-mask delay. The delay corresponding to the inflexion point of the sigmoid, where visibility suddenly increases, was termed the " non-linear transition threshold " and used as a summary measure of masking efficiency. Objective and subjective non-linear transition thresholds were highly correlated across subjects in both groups, and were higher in patients compared to controls. In patients, variations in the non-linear transition threshold were inversely correlated to the Magnetization transfer ratio (MTR) values inside the right dorsolateral prefrontal WM, the right occipito-frontal fasciculus and the left cerebellum. This study provides clinical evidence of a relationship between impairments of conscious access and integrity of large WM bundles, particularly involving prefrontal cortex, as predicted by global neuronal workspace theory. Introduction Understanding neural mechanisms underlying conscious perception remains an unsolved question in cognitive neuroscience. Whether conscious perception is an early phenomenon localized in posterior occipital and temporal brain areas or whether it requires a larger network involving anterior frontal and parietal areas is still controversial. In fact, some theoretical models support an essential role of distributed long-distance brain networks in visual awareness These models have been corroborated by functional neuroimaging studies showing that access of sensory stimuli to conscious report correlated with the activation of higher associative cortices, particularly parietal, prefrontal and anterior cin-Sergent et al., 2005). In particular, backward masking paradigm, in which the visibility of a briefly flashed stimulus is reduced when followed after a short delay by a second stimulus called the mask, has been used to differentiate conscious from non-conscious processing of visual stimuli. Dehaene et al. (2001) showed in an fMRI study using …

[1]  S. Dehaene,et al.  White matter damage impairs access to consciousness in multiple sclerosis , 2009, NeuroImage.

[2]  André Ali Chérif,et al.  Intact subliminal processing and delayed conscious access in multiple sclerosis , 2007, Neuropsychologia.

[3]  Deepak N. Pandya,et al.  The occipitofrontal fascicle in humans: A quantitative, in vivo, DT-MRI study , 2007, NeuroImage.

[4]  S. Dehaene,et al.  Brain Dynamics Underlying the Nonlinear Threshold for Access to Consciousness , 2007, PLoS biology.

[5]  Alexander Maye,et al.  Temporal dynamics of access to consciousness in the attentional blink , 2007, NeuroImage.

[6]  D. Louis Collins,et al.  Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion , 2007, NeuroImage.

[7]  Bertrand Audoin,et al.  Structure of WM bundles constituting the working memory system in early multiple sclerosis: A quantitative DTI tractography study , 2007, NeuroImage.

[8]  Stanislas Dehaene,et al.  Preserved subliminal processing and impaired conscious access in schizophrenia. , 2006, Archives of general psychiatry.

[9]  S. Dehaene,et al.  Conscious, preconscious, and subliminal processing: a testable taxonomy , 2006, Trends in Cognitive Sciences.

[10]  David H. Miller,et al.  Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis. , 2006, Brain : a journal of neurology.

[11]  D. Pandya,et al.  Fiber Pathways of the Brain , 2006 .

[12]  Paul M Matthews,et al.  Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. , 2006, Brain : a journal of neurology.

[13]  R. Mccoll,et al.  Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity , 2005, NeuroImage.

[14]  My-Van Au Duong,et al.  Altered Functional Connectivity Related to White Matter Changes inside the Working Memory Network at the Very Early Stage of MS , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  S. Dehaene,et al.  Timing of the brain events underlying access to consciousness during the attentional blink , 2005, Nature Neuroscience.

[16]  J. Driver,et al.  Visibility Reflects Dynamic Changes of Effective Connectivity between V1 and Fusiform Cortex , 2005, Neuron.

[17]  Bertrand Audoin,et al.  Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis , 2005, Human brain mapping.

[18]  Bertrand Audoin,et al.  Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis , 2005, NeuroImage.

[19]  S. Dehaene,et al.  Is Consciousness a Gradual Phenomenon? Evidence for an All-or-None Bifurcation During the Attentional Blink , 2004 .

[20]  My-Van Au Duong,et al.  Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis , 2004, Journal of magnetic resonance imaging : JMRI.

[21]  Kimron Shapiro,et al.  Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Martin P Paulus,et al.  From sensory processes to conscious perception , 2004, Consciousness and Cognition.

[23]  J B Poline,et al.  Letter Binding and Invariant Recognition of Masked Words , 2004, Psychological science.

[24]  M. Chun,et al.  The Neural Fate of Consciously Perceived and Missed Events in the Attentional Blink , 2004, Neuron.

[25]  J. Changeux,et al.  A neuronal network model linking subjective reports and objective physiological data during conscious perception , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C H Polman,et al.  The Brief Repeatable Battery of Neuropsychological Tests: normative values allow application in multiple sclerosis clinical practice , 2001, Multiple sclerosis.

[27]  J B Poline,et al.  Cerebral mechanisms of word masking and unconscious repetition priming , 2001, Nature Neuroscience.

[28]  S. Dehaene,et al.  Unconscious semantic priming extends to novel unseen stimuli , 2001, Cognition.

[29]  C. Frith,et al.  Neural correlates of change detection and change blindness , 2001, Nature Neuroscience.

[30]  J. Eastwood,et al.  Perception without awareness: perspectives from cognitive psychology , 2001, Cognition.

[31]  S. Dehaene,et al.  Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework , 2001, Cognition.

[32]  M Cercignani,et al.  Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis , 2001, Journal of neurology, neurosurgery, and psychiatry.

[33]  B. Breitmeyer,et al.  Recent models and findings in visual backward masking: A comparison, review, and update , 2000, Perception & psychophysics.

[34]  Ronald A. Rensink,et al.  Competition for consciousness among visual events: the psychophysics of reentrant visual processes. , 2000, Journal of experimental psychology. General.

[35]  G. Comi,et al.  Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI , 2000, Neurology.

[36]  Nikos Evangelou,et al.  Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis , 2000, Annals of neurology.

[37]  M Filippi,et al.  A magnetization transfer histogram study of normal-appearing brain tissue in MS , 2000, Neurology.

[38]  F. Barkhof,et al.  Axonal loss in multiple sclerosis lesions: Magnetic resonance imaging insights into substrates of disability , 1999, Annals of neurology.

[39]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[40]  G. Rees,et al.  Covariation of activity in visual and prefrontal cortex associated with subjective visual perception. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S Dehaene,et al.  A neuronal model of a global workspace in effortful cognitive tasks. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Richard L. Abrams,et al.  Three Cognitive Markers of Unconscious Semantic Activation , 1996, Science.

[43]  P. Merikle,et al.  Priming with and without awareness , 1984, Perception & psychophysics.

[44]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[45]  I. Allen,et al.  A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis , 1979, Journal of the Neurological Sciences.

[46]  J. R. Doyle Semantic activation without conscious identification in dichotic listening , parafoveal vision , and visual masking : A survey and appraisal , 2008 .

[47]  J. Ranjeva,et al.  Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. , 2005, AJNR. American journal of neuroradiology.

[48]  L. Martí-Bonmatí,et al.  Spectroscopic axonal damage of the right locus coeruleus relates to selective attention impairment in early stage relapsing-remitting multiple sclerosis. , 2004, Brain : a journal of neurology.