Sequential neural changes during motor learning in schizophrenia

Positron emission tomography (PET) was used to investigate differences in neural plasticity associated with learning a unique motor task in patients with schizophrenia and healthy volunteers. Working with a robotic manipulandum, subjects learned reaching movements in a force field. Visual cues were provided to guide the reaching movements. PET rCBF measures were acquired while participants learned the motor skill over successive runs. The groups did not differ in behavioral performance but did differ in their rCBF activity patterns. Healthy volunteers displayed blood flow increases in primary motor cortex and supplementary motor area with motor learning. The patients with schizophrenia displayed an increase in the primary visual cortex with motor learning. Changes in these regions were positively correlated with changes in each group's motor accuracy, respectively. This is the first study to employ a unique arm-reaching motor learning test to assess neural plasticity during multiple phases of motor learning in patients with schizophrenia. The patients may have an inability to rapidly tune motor cortical neural populations to a preferred direction. The visual system, however, appears to be highly compensated in schizophrenia and the inability to rapidly modulate the motor cortex may be substantially corrected by the schizophrenic group's visuomotor adaptations.

[1]  E. Bizzi,et al.  Postural force fields of the human arm and their role in generating multijoint movements , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  R. Shadmehr,et al.  Inhibitory control of competing motor memories , 1999, Experimental Brain Research.

[3]  H. Olpe,et al.  Effects of subchronic clozapine treatment on long-term potentiation in rat prefrontal cortex , 2004, European Neuropsychopharmacology.

[4]  G. Teskey,et al.  Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation , 2004, Neuroscience.

[5]  Deborah A. Yurgelun-Todd,et al.  Functional magnetic resonance imaging in schizophrenia: cortical response to motor stimulation , 2004, Psychiatry Research: Neuroimaging.

[6]  G. Buzsáki,et al.  Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies , 2006, Neuron.

[7]  E. Vaadia,et al.  Preparatory activity in motor cortex reflects learning of local visuomotor skills , 2003, Nature Neuroscience.

[8]  Yasmin L. Hashambhoy,et al.  Neural Correlates of Reach Errors , 2005, The Journal of Neuroscience.

[9]  Leslie G. Ungerleider,et al.  Imaging Brain Plasticity during Motor Skill Learning , 2002, Neurobiology of Learning and Memory.

[10]  M. Fahle Perceptual learning: specificity versus generalization , 2005, Current Opinion in Neurobiology.

[11]  R. Johansson,et al.  Prediction Precedes Control in Motor Learning , 2003, Current Biology.

[12]  Karl J. Friston,et al.  Tests for Distributed, Nonfocal Brain Activations , 1995, NeuroImage.

[13]  A. Karni,et al.  The time course of learning a visual skill , 1993, Nature.

[14]  R. Shadmehr Generalization as a behavioral window to the neural mechanisms of learning internal models. , 2004, Human movement science.

[15]  Peter Herscovitch,et al.  Brain blood flow measured with intravenous H/sub 2//sup 15/O. I. Theory and error analysis , 1983 .

[16]  Reza Shadmehr,et al.  Internal models of limb dynamics and the encoding of limb state , 2005, Journal of neural engineering.

[17]  T. Brashers-Krug,et al.  Functional Stages in the Formation of Human Long-Term Motor Memory , 1997, The Journal of Neuroscience.

[18]  E. Bizzi,et al.  Neuronal activity in the supplementary motor area of monkeys adapting to a new dynamic environment. , 2004, Journal of neurophysiology.

[19]  B J Geesaman,et al.  Maps of complex motion selectivity in the superior temporal cortex of the alert macaque monkey: a double-label 2-deoxyglucose study. , 1997, Cerebral cortex.

[20]  K. Takenouchi,et al.  Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging , 2001, Psychological Medicine.

[21]  R. Malenka,et al.  Central error-correcting behavior in schizophrenia and depression , 1986, Biological Psychiatry.

[22]  S. Deutsch,et al.  Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction , 1996, Biological Psychiatry.

[23]  D. Wolpert,et al.  Explaining the symptoms of schizophrenia: Abnormalities in the awareness of action , 2000, Brain Research Reviews.

[24]  Claude Alain,et al.  Neurophysiological evidence of error-monitoring deficits in patients with schizophrenia. , 2002, Cerebral cortex.

[25]  Gabriele Ende,et al.  Cortical response to motor stimulation in neuroleptic-naive first episode schizophrenics , 2000, Psychiatry Research: Neuroimaging.

[26]  P. Strick,et al.  Multiple output channels in the basal ganglia. , 1993, Science.

[27]  R. Shadmehr,et al.  Long-term adaptation to dynamics of reaching movements: a PET study , 2001, Experimental Brain Research.

[28]  M. Hallett,et al.  Frontal and parietal networks for conditional motor learning: a positron emission tomography study. , 1997, Journal of neurophysiology.

[29]  L. Elliot Hong,et al.  Specific motion processing pathway deficit during eye tracking in schizophrenia: A performance-matched functional magnetic resonance imaging study , 2005, Biological Psychiatry.

[30]  Eilon Vaadia,et al.  Viewing and doing: similar cortical mechanisms for perceptual and motor learning , 2004, Trends in Neurosciences.

[31]  M. Hallett,et al.  Early consolidation in human primary motor cortex , 2002, Nature.

[32]  R Shadmehr,et al.  Time-dependent motor memory processes in amnesic subjects. , 1998, Journal of neurophysiology.

[33]  Leslie G. Ungerleider,et al.  Functional MRI evidence for adult motor cortex plasticity during motor skill learning , 1995, Nature.

[34]  E. Bizzi,et al.  Consolidation in human motor memory , 1996, Nature.

[35]  R. Shadmehr,et al.  Interacting Adaptive Processes with Different Timescales Underlie Short-Term Motor Learning , 2006, PLoS biology.

[36]  R Shadmehr,et al.  Spatial Generalization from Learning Dynamics of Reaching Movements , 2000, The Journal of Neuroscience.

[37]  E. Bullmore,et al.  Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation , 2002, Schizophrenia Research.

[38]  Carsten Schmidt-Samoa,et al.  Reduced size of the pre-supplementary motor cortex and impaired motor sequence learning in first-episode schizophrenia , 2006, Schizophrenia Research.

[39]  Leslie G. Ungerleider,et al.  Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning , 2003, Neuropsychologia.

[40]  G. Orban,et al.  Charting the Lower Superior Temporal Region, a New Motion-Sensitive Region in Monkey Superior Temporal Sulcus , 2006, The Journal of Neuroscience.

[41]  C. Carter,et al.  Anterior cingulate cortex activity and impaired self-monitoring of performance in patients with schizophrenia: an event-related fMRI study. , 2001, The American journal of psychiatry.

[42]  D. Wolpert,et al.  Evidence for sensory prediction deficits in schizophrenia. , 2005, The American journal of psychiatry.

[43]  G. Schuierer,et al.  Motor-induced brain activation in cortical, subcortical and cerebellar regions in schizophrenic inpatients. A whole brain fMRI fingertapping study , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[44]  Karl J. Friston,et al.  Combining Spatial Extent and Peak Intensity to Test for Activations in Functional Imaging , 1997, NeuroImage.

[45]  M. Laubach,et al.  Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task , 2022 .

[46]  Tomaso Poggio,et al.  Generalization in vision and motor control , 2004, Nature.

[47]  P. Gribble,et al.  Are there distinct neural representations of object and limb dynamics? , 2006, Experimental Brain Research.

[48]  J. Donoghue,et al.  Strengthening of horizontal cortical connections following skill learning , 1998, Nature Neuroscience.

[49]  Leslie G. Ungerleider,et al.  Cortical connections of visual area MT in the macaque , 1986, The Journal of comparative neurology.

[50]  H. Eichenbaum,et al.  Spatial and behavioral correlates of hippocampal neuronal activity , 1989 .

[51]  H. Komatsu,et al.  Relation of cortical areas MT and MST to pursuit eye movements. I. Localization and visual properties of neurons. , 1988, Journal of neurophysiology.

[52]  A. Pfefferbaum,et al.  A deficit profile of executive, memory, and motor functions in schizophrenia , 1994, Biological Psychiatry.

[53]  F A Mussa-Ivaldi,et al.  Adaptive representation of dynamics during learning of a motor task , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  J. Malley,et al.  Habit and skill learning in schizophrenia: evidence of normal striatal processing with abnormal cortical input. , 2002, Learning & memory.

[55]  P. Strick,et al.  Basal-ganglia 'projections' to the prefrontal cortex of the primate. , 2002, Cerebral cortex.

[56]  B. Turetsky,et al.  Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. , 2007, The American journal of psychiatry.

[57]  E. Bizzi,et al.  Neuronal Correlates of Motor Performance and Motor Learning in the Primary Motor Cortex of Monkeys Adapting to an External Force Field , 2001, Neuron.

[58]  S. Wise,et al.  Evolution of Directional Preferences in the Supplementary Eye Field during Acquisition of Conditional Oculomotor Associations , 1996, The Journal of Neuroscience.

[59]  D. Wolpert,et al.  Abnormalities in the awareness and control of action. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[60]  Karl J. Friston,et al.  Estimating Smoothness in Statistical Parametric Maps: Variability of p Values , 1995, Journal of computer assisted tomography.

[61]  J. Mather,et al.  Motor control of schizophrenics--II. Manual control and tracking: sensory and motor deficits. , 1984, Journal of psychiatric research.

[62]  Scott T. Grafton,et al.  Dorsal premotor cortex and conditional movement selection: A PET functional mapping study. , 1998, Journal of neurophysiology.

[63]  L. Schad,et al.  Sensorimotor Cortex and Supplementary Motor Area Changes in Schizophrenia , 1995, British Journal of Psychiatry.

[64]  Andreas Keil,et al.  Dynamical aspects of motor and perceptual processes in schizophrenic patients and healthy controls , 1998, Schizophrenia Research.

[65]  Lothar R. Schad,et al.  Motor Dysfunction and Sensorimotor Cortex Activation Changes in Schizophrenia: A Study with Functional Magnetic Resonance Imaging , 1999, NeuroImage.

[66]  Leslie G. Ungerleider,et al.  The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[67]  R. Shadmehr,et al.  Neural correlates of motor memory consolidation. , 1997, Science.

[68]  Bao-Ming Li,et al.  Deficit in conditional visuomotor learning by local infusion of bicuculline into the ventral prefrontal cortex in monkeys , 2000, The European journal of neuroscience.

[69]  R. Wurtz,et al.  A Pathway in Primate Brain for Internal Monitoring of Movements , 2002, Science.

[70]  J A Frank,et al.  Abnormal functional lateralization of the sensorimotor cortex in patients with schizophrenia , 1997, Neuroreport.

[71]  P. Matthews,et al.  Changing brain networks for visuomotor control with increased movement automaticity. , 2004, Journal of neurophysiology.

[72]  Tamar Flash,et al.  Multiple shifts in the representation of a motor sequence during the acquisition of skilled performance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[73]  S P Wise,et al.  The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta). , 2001, Behavioral neuroscience.

[74]  M. Mintun,et al.  Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[75]  Henry H. Holcomb,et al.  Practice, learning, and the likelihood of making an error: how task experience shapes physiological response in patients with schizophrenia , 2004, Psychopharmacology.

[76]  P. Matthews,et al.  Distinguishable brain activation networks for short- and long-term motor skill learning. , 2005, Journal of neurophysiology.

[77]  Gabriele Ende,et al.  Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients , 1999, Schizophrenia Research.

[78]  J. Tanji,et al.  Activity in the Lateral Prefrontal Cortex Reflects Multiple Steps of Future Events in Action Plans , 2006, Neuron.

[79]  P. Maruff,et al.  Attention, motor control and motor imagery in schizophrenia: implications for the role of the parietal cortex , 2004, Schizophrenia Research.

[80]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[81]  Michael I. Jordan,et al.  An internal model for sensorimotor integration. , 1995, Science.

[82]  E. Bizzi,et al.  Cortical correlates of learning in monkeys adapting to a new dynamical environment. , 2000, Proceedings of the National Academy of Sciences of the United States of America.