Evidence for metaplasticity in the human visual cortex

The threshold and direction of excitability changes induced by low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) in the primary motor cortex can be effectively reverted by a preceding session of transcranial direct current stimulation (tDCS), a phenomenon referred to as “metaplasticity”. Here, we used a combined tDCS–rTMS protocol and visual evoked potentials (VEPs) in healthy subjects to provide direct electrophysiological evidence for metaplasticity in the human visual cortex. Specifically, we evaluated changes in VEPs at two different contrasts (90 and 20 %) before and at different time points after the application of anodal or cathodal tDCS to occipital cortex (i.e., priming), followed by an additional conditioning with low- or high-frequency rTMS. Anodal tDCS increased the amplitude of VEPs and this effect was paradoxically reverted by applying high-frequency (5 Hz), conventionally excitatory rTMS (p < 0.0001). Similarly, cathodal tDCS led to a decrease in VEPs amplitude, which was reverted by a subsequent application of conventionally inhibitory, 1 Hz rTMS (p < 0.0001). Similar changes were observed for both the N1 and P1 component of the VEP. There were no significant changes in resting motor threshold values (p > 0.5), confirming the spatial selectivity of our conditioning protocol. Our findings show that preconditioning primary visual area excitability with tDCS can modulate the direction and strength of plasticity induced by subsequent application of 1 or 5 Hz rTMS. These data indicate the presence of mechanisms of metaplasticity that keep synaptic strengths within a functional dynamic range in the human visual cortex.

[1]  M. Ptito,et al.  TMS of the occipital cortex induces tactile sensations in the fingers of blind Braille readers , 2007, Experimental Brain Research.

[2]  Lisa Koski,et al.  Report Brain Plasticity in the Adult: Modulation of Function in Amblyopia with Rtms , 2022 .

[3]  S. Rossi,et al.  Transcallosal inhibition dampens neural responses to high contrast stimuli in human visual cortex , 2011, Neuroscience.

[4]  C. C. Law,et al.  Formation of receptive fields in realistic visual environments according to the Bienenstock, Cooper, and Munro (BCM) theory. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Martin Eimer,et al.  The neural signature of phosphene perception , 2010, Human brain mapping.

[6]  B. Fierro,et al.  Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation , 2002, Experimental Brain Research.

[7]  Vittorio Porciatti,et al.  Normative data for onset VEPs to red-green and blue-yellow chromatic contrast , 1999, Clinical Neurophysiology.

[8]  R. Sadleir,et al.  Predicted current densities in the brain during transcranial electrical stimulation , 2006, Clinical Neurophysiology.

[9]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[10]  H. Spekreijse,et al.  Standard for Visual Evoked Potentials 1995 , 1996, Vision Research.

[11]  S. Tobimatsu,et al.  Studies of human visual pathophysiology with visual evoked potentials , 2006, Clinical Neurophysiology.

[12]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[13]  Dennis J. L. G. Schutter,et al.  Retinal origin of phosphenes to transcranial alternating current stimulation , 2010, Clinical Neurophysiology.

[14]  Walter Paulus,et al.  Facilitation of visuo‐motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans , 2004, The European journal of neuroscience.

[15]  F. Bandini,et al.  The visuo-cognitive and motor effect of amantadine in non-Caucasian patients with Parkinson's disease. A clinical and electrophysiological study , 2002, Journal of Neural Transmission.

[16]  M. Nitsche,et al.  Pharmacological Modulation of Cortical Excitability Shifts Induced by Transcranial Direct Current Stimulation in Humans , 2003, The Journal of physiology.

[17]  Á. Pascual-Leone,et al.  Fast Backprojections from the Motion to the Primary Visual Area Necessary for Visual Awareness , 2001, Science.

[18]  C. Miniussi,et al.  Random Noise Stimulation Improves Neuroplasticity in Perceptual Learning , 2011, The Journal of Neuroscience.

[19]  W. Abraham.  Metaplasticity: tuning synapses and networks for plasticity , 2008, Nature Reviews Neuroscience.

[20]  Albert Gjedde,et al.  Erratum: Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects (Proceedings of the National Academy of Sciences of the United States of America (August 29, 2006) 103, 35 (13256-13260) DOI: 10.1073/pnas.0602925103) , 2006 .

[21]  L. Bindman,et al.  The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long‐lasting after‐effects , 1964, The Journal of physiology.

[22]  A. Schleicher,et al.  Transmitter receptors and functional anatomy of the cerebral cortex , 2004, Journal of anatomy.

[23]  N Accornero,et al.  Polarization of the human motor cortex through the scalp , 1998, Neuroreport.

[24]  G. Cosentino,et al.  Does habituation depend on cortical inhibition? Results of a rTMS study in healthy subjects , 2011, Experimental Brain Research.

[25]  M. Bear,et al.  Promoting neurological recovery of function via metaplasticity. , 2010, Future neurology.

[26]  Robert Chen,et al.  Short interval intracortical inhibition and facilitation during the silent period in human , 2007, The Journal of physiology.

[27]  R. Racine,et al.  Long-Term Depression and Depotentiation in the Sensorimotor Cortex of the Freely Moving Rat , 2000, The Journal of Neuroscience.

[28]  J. Schoenen,et al.  Deficient habituation of evoked cortical potentials in migraine: a link between brain biology, behavior and trigeminovascular activation? , 1996, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[29]  I. Bodis-Wollner,et al.  Cortical contrast gain control in human spatial vision. , 1988, The Journal of physiology.

[30]  M. Hallett,et al.  Depression of motor cortex excitability by low‐frequency transcranial magnetic stimulation , 1997, Neurology.

[31]  H. Shouval,et al.  Structural Plasticity Can Produce Metaplasticity , 2009, PloS one.

[32]  B. Greenberg,et al.  Menstrual cycle effects on cortical excitability , 1999, Neurology.

[33]  David C. Burr,et al.  Brief periods of monocular deprivation disrupt ocular balance in human adult visual cortex , 2011, Current Biology.

[34]  Pieter R Roelfsema,et al.  The role of primary visual cortex (V1) in visual awareness , 2000, Vision Research.

[35]  Á. Pascual-Leone,et al.  Modulatory effects of low‐ and high‐frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation , 2005, The Journal of physiology.

[36]  O. Creutzfeldt,et al.  Influence of transcortical d-c currents on cortical neuronal activity. , 1962, Experimental neurology.

[37]  Niraj S. Desai,et al.  Homeostatic plasticity in the CNS: synaptic and intrinsic forms , 2003, Journal of Physiology-Paris.

[38]  M. Hallett,et al.  Modeling the current distribution during transcranial direct current stimulation , 2006, Clinical Neurophysiology.

[39]  Walter Paulus,et al.  Transcranial direct current stimulation and the visual cortex , 2006, Brain Research Bulletin.

[40]  L. Cohen,et al.  Enhanced excitability of the human visual cortex induced by short-term light deprivation. , 2000, Cerebral cortex.

[41]  Walter Paulus,et al.  Bidirectional modulation of primary visual cortex excitability: a combined tDCS and rTMS study. , 2007, Investigative ophthalmology & visual science.

[42]  Claire E. J. Cheetham,et al.  Homeostatic plasticity mechanisms are required for juvenile, but not adult, ocular dominance plasticity , 2012, Proceedings of the National Academy of Sciences.

[43]  J. Rothwell,et al.  Preconditioning of Low-Frequency Repetitive Transcranial Magnetic Stimulation with Transcranial Direct Current Stimulation: Evidence for Homeostatic Plasticity in the Human Motor Cortex , 2004, The Journal of Neuroscience.

[44]  Carlo Miniussi,et al.  The neural mechanisms of the effects of transcranial magnetic stimulation on perception. , 2010, Journal of neurophysiology.

[45]  E. Bienenstock,et al.  Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  M. Ghilardi,et al.  N70 and P100 can be independently affected in multiple sclerosis. , 1991, Electroencephalography and clinical neurophysiology.

[47]  Juha Silvanto,et al.  Stimulation of the human frontal eye fields modulates sensitivity of extrastriate visual cortex. , 2006, Journal of neurophysiology.

[48]  M. Nitsche,et al.  Safety criteria for transcranial direct current stimulation (tDCS) in humans , 2003, Clinical Neurophysiology.

[49]  G. Turrigiano.  Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement. , 2011, Annual review of neuroscience.

[50]  M. Bear,et al.  Metaplasticity: the plasticity of synaptic plasticity , 1996, Trends in Neurosciences.

[51]  M. Bear,et al.  Visual Experience and Deprivation Bidirectionally Modify the Composition and Function of NMDA Receptors in Visual Cortex , 2001, Neuron.

[52]  Brian N. Pasley,et al.  State-Dependent Variability of Neuronal Responses to Transcranial Magnetic Stimulation of the Visual Cortex , 2009, Neuron.

[53]  B. Sabel.  Plasticity and restoration of vision after visual system damage: an update. , 2008, Restorative neurology and neuroscience.

[54]  Simone Rossi,et al.  Transcranial magnetic stimulation , 2007, Neurology.

[55]  J. Rothwell,et al.  Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects , 2004, Biological Psychiatry.

[56]  Simone Rossi,et al.  Cortico-Cortical Connectivity between Right Parietal and Bilateral Primary Motor Cortices during Imagined and Observed Actions: A Combined TMS/tDCS Study , 2011, Front. Neural Circuits.

[57]  M. Nitsche,et al.  Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. , 2002, Brain : a journal of neurology.

[58]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[59]  M. Bear,et al.  Experience-dependent modification of synaptic plasticity in visual cortex , 1996, Nature.

[60]  M. Nitsche,et al.  GABAergic modulation of DC stimulation‐induced motor cortex excitability shifts in humans , 2004, The European journal of neuroscience.

[61]  Walter Paulus,et al.  Transcranial Direct Current Stimulation and Visual Perception , 2008, Perception.

[62]  V. Lamme,et al.  The distinct modes of vision offered by feedforward and recurrent processing , 2000, Trends in Neurosciences.

[63]  L. Maffei,et al.  Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity , 2007, The Journal of Neuroscience.

[64]  Sarah H Lisanby,et al.  Therapeutic application of repetitive transcranial magnetic stimulation: a review , 2001, Clinical Neurophysiology.

[65]  Mark F Bear,et al.  Evidence for Altered NMDA Receptor Function as a Basis for Metaplasticity in Visual Cortex , 2003, The Journal of Neuroscience.

[66]  Steven A. Hillyard,et al.  Identification of the neural sources of the pattern-reversal VEP , 2005, NeuroImage.

[67]  H. Spekreijse,et al.  Standard for visual evoked potentials 1995. The International Society for Clinical Electrophysiology of Vision. , 1996, Vision research.

[68]  J. Schoenen,et al.  Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine. , 2002, Brain : a journal of neurology.

[69]  G. Turrigiano.  The Self-Tuning Neuron: Synaptic Scaling of Excitatory Synapses , 2008, Cell.

[70]  S. Nelson,et al.  Hebb and homeostasis in neuronal plasticity , 2000, Current Opinion in Neurobiology.