The benefits of cholinergic enhancement during perceptual learning are long-lasting

The neurotransmitter acetylcholine (ACh) regulates many aspects of cognition, including attention and memory. Previous research in animal models has shown that plasticity in sensory systems often depends on the behavioral relevance of a stimulus and/or task. However, experimentally increasing ACh release in the cortex can result in experience-dependent plasticity, even in the absence of behavioral relevance. In humans, the pharmacological enhancement of ACh transmission by administration of the cholinesterase inhibitor donepezil during performance of a perceptual task increases the magnitude of perceptual learning (PL) and its specificity to physical parameters of the stimuli used for training. Behavioral effects of PL have previously been shown to persist for many months. In the present study, we tested whether enhancement of PL by donepezil is also long-lasting. Healthy human subjects were trained on a motion direction discrimination task during cholinergic enhancement, and follow-up testing was performed 5–15 months after the end of training and without additional drug administration. Increases in performance associated with training under donepezil were evident in follow-up retesting, indicating that cholinergic enhancement has beneficial long-term effects on PL. These findings suggest that cholinergic enhancement of training procedures used to treat clinical disorders should improve long-term outcomes of these procedures.

[1]  Aaron R. Seitz,et al.  Psychophysics: Is subliminal learning really passive? , 2003, Nature.

[2]  B. Feige,et al.  Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers , 2006, Neuropsychopharmacology.

[3]  Dennis M. Levi,et al.  Decoupling location specificity from perceptual learning of orientation discrimination , 2010, Vision Research.

[4]  J. Hobson,et al.  Visual Discrimination Task Improvement: A Multi-Step Process Occurring During Sleep , 2000, Journal of Cognitive Neuroscience.

[5]  S. Klein,et al.  Rule-Based Learning Explains Visual Perceptual Learning and Its Specificity and Transfer , 2010, The Journal of Neuroscience.

[6]  B. Dosher,et al.  Mechanisms of perceptual learning , 1999, Vision Research.

[7]  Pengjing Xu,et al.  Perceptual learning improves contrast sensitivity and visual acuity in adults with anisometropic amblyopia , 2006, Vision Research.

[8]  A. Baddeley,et al.  Context-dependent memory in two natural environments: on land and underwater. , 1975 .

[9]  M. Kilgard,et al.  Cortical map reorganization enabled by nucleus basalis activity. , 1998, Science.

[10]  J. Maunsell,et al.  The Effect of Perceptual Learning on Neuronal Responses in Monkey Visual Area V4 , 2004, The Journal of Neuroscience.

[11]  Aaron R. Seitz,et al.  A common framework for perceptual learning , 2007, Current Opinion in Neurobiology.

[12]  R. Sekuler,et al.  A specific and enduring improvement in visual motion discrimination. , 1982, Science.

[13]  S. Hochstein,et al.  Attentional control of early perceptual learning. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[14]  E. Ahissar,et al.  A neuronal analogue of state-dependent learning , 2000, Nature.

[15]  A. Watson,et al.  Quest: A Bayesian adaptive psychometric method , 1983, Perception & psychophysics.

[16]  M. Lai,et al.  Neurochemical basis for symptomatic treatment of Alzheimer's disease , 2010, Neuropharmacology.

[17]  Takeo Watanabe,et al.  Perceptual learning without perception , 2001, Nature.

[18]  D. Sagi.  Perceptual learning in Vision Research , 2011, Vision Research.

[19]  M. Sarter,et al.  Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention , 2002, Neuroscience.

[20]  T. Iwasaki,et al.  Involvement of benzodiazepine/GABA-A receptor complex in ethanol-induced state-dependent learning in rats , 1995, Brain Research.

[21]  M. Merzenich,et al.  Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  S. Klein,et al.  Complete Transfer of Perceptual Learning across Retinal Locations Enabled by Double Training , 2008, Current Biology.

[23]  A. Landau,et al.  Cholinergic Enhancement Increases the Effects of Voluntary Attention but Does Not Affect Involuntary Attention , 2010, Neuropsychopharmacology.

[24]  M. Hasselmo,et al.  Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition , 2011, Neuropsychopharmacology.

[25]  Takeo Watanabe,et al.  Perceptual learning rules based on reinforcers and attention , 2010, Trends in Cognitive Sciences.

[26]  G. Orban,et al.  Practising orientation identification improves orientation coding in V1 neurons , 2001, Nature.

[27]  Michael Belkin,et al.  Improving vision in adult amblyopia by perceptual learning. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D G Pelli,et al.  The VideoToolbox software for visual psychophysics: transforming numbers into movies. , 1997, Spatial vision.

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

[30]  M. Greenlee,et al.  Nicotine facilitates memory consolidation in perceptual learning , 2013, Neuropharmacology.

[31]  Aaron R. Seitz,et al.  The phenomenon of task-irrelevant perceptual learning , 2009, Vision Research.

[32]  R. Sekuler,et al.  Direction-specific improvement in motion discrimination , 1987, Vision Research.

[33]  Louise S. Delicato,et al.  Acetylcholine contributes through muscarinic receptors to attentional modulation in V1 , 2008, Nature.

[34]  M. Silver,et al.  Cholinergic Enhancement Augments Magnitude and Specificity of Visual Perceptual Learning in Healthy Humans , 2010, Current Biology.

[35]  J. Mollon,et al.  Three remarks on perceptual learning. , 1996, Spatial vision.

[36]  B. Everitt,et al.  AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  Lisa M. Giocomo,et al.  Neuromodulation by Glutamate and Acetylcholine can Change Circuit Dynamics by Regulating the Relative Influence of Afferent Input and Excitatory Feedback , 2007, Molecular Neurobiology.

[38]  D Sagi,et al.  Where practice makes perfect in texture discrimination: evidence for primary visual cortex plasticity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Dennis M. Levi,et al.  Perceptual learning as a potential treatment for amblyopia: A mini-review , 2009, Vision Research.

[40]  D H Brainard,et al.  The Psychophysics Toolbox. , 1997, Spatial vision.

[41]  B. Dosher,et al.  Mechanisms of perceptual learning , 1999, Vision Research.

[42]  W. Singer,et al.  Pharmacological induction of use-dependent receptive field modifications in the visual cortex. , 1988, Science.

[43]  Ariel Rokem,et al.  A model of encoding and decoding in V1 and MT accounts for motion perception anisotropies in the human visual system , 2009, Brain Research.