Trends in Neurosciences
Volume 35, Issue 12, December 2012, Pages 715-722
Journal home page for Trends in Neurosciences

Opinion
Harnessing plasticity to understand learning and treat disease

https://doi.org/10.1016/j.tins.2012.09.002Get rights and content

A large body of evidence suggests that neural plasticity contributes to learning and disease. Recent studies suggest that cortical map plasticity is typically a transient phase that improves learning by increasing the pool of task-relevant responses. Here, I discuss a new perspective on neural plasticity and suggest how plasticity might be targeted to reset dysfunctional circuits. Specifically, a new model is proposed in which map expansion provides a form of replication with variation that supports a Darwinian mechanism to select the most behaviorally useful circuits. Precisely targeted neural plasticity provides a new avenue for the treatment of neurological and psychiatric disorders and is a powerful tool to test the neural mechanisms of learning and memory.

Introduction

Neurological and psychiatric disorders account for one-third of the total disease burden in the developed world [1]. Current surgical, behavioral, and pharmacological treatments generally lack the power and precision necessary to modify aberrant circuits and restore normal function. Effective treatments are possible if tools can be developed that operate at the same temporal and spatial scales as the brain (i.e., milliseconds and micrometers). The first half of this article summarizes the evidence that precisely timed release of neuromodulators may prove to be a valuable tool to manipulate fine-scale neural connectivity in humans. In the second half, I propose a new perspective on brain function that may explain a range of apparently contradictory observations related to cortical map plasticity associated with learning and disease.

Section snippets

Reversing pathological brain plasticity

Although neural plasticity is generally viewed as an adaptive process, there is considerable evidence that plasticity can also be maladaptive 2, 3, 4, 5. For example, brain changes in response to nerve damage or cochlear trauma appear to be responsible for many types of chronic pain and tinnitus. Significant injury-induced changes in map organization, spontaneous activity, neural synchronization, and stimulus selectivity have been observed in multiple regions of the central nervous system 2, 4.

A functional role for map plasticity

An important factor limiting the potential of directed plasticity to treat neurological and psychiatric conditions is an inadequate understanding of neural coding and the role that neural plasticity plays in learning and in disease. For example, despite the key historical role of map plasticity studies in advancing understanding of neural plasticity, the function of map plasticity in associative or skill learning remains uncertain.

A few weeks of training of humans or animals on a task that

Learning as a Darwinian process

The Expansion–Renormalization model is based on principles of Darwinian selection. In ecosystems and market economies, the Darwinian two-step model [i.e., (i) replication with variation; and (ii) selection] is highly effective at generating robust and complex networks 69, 70. Given the power and flexibility of evolutionary algorithms, it is surprising that map plasticity has not been seriously entertained as a source of replication with variation upon which reinforcement-based selection could

Model predictions

This new model is able to account for a diverse set of findings that were poorly explained by earlier models of learning and plasticity, and makes specific testable predictions.

  • (i)

    A Darwinian system explains how map expansion speeds learning without being necessary for task performance [12].

  • (ii)

    This model explains why blocking map plasticity slows, but does not prevent, new learning [46].

  • (iii)

    Storage of new skills and memories in small stable networks can explain the low degree of interference among large

Concluding remarks

New insights into the regulation and expression of neural plasticity are likely to aid the refinement of plasticity-based therapies to treat a variety of brain disorders. It is possible that the neural exploration mechanisms that support learning can sometimes lead to pathological networks that are maladaptive. Depending on the connectivity of neurons in the network, pathological spontaneous activity in a small population could trigger disturbing phantoms sensations, such as tinnitus, pain,

Acknowledgments

A special thanks to Aage Moller, Dean Buonomano, Dirk De Ridder, Robert Liu, Robert Rennaker, Jonathan Fritz, Larry Cauller, Navzer Engineer, Tracy Rosen, Jonathan Ploski, Kamalini Ranasinghe, Christa McIntyre, Crystal Engineer, Amanda Reed, and Mike Deweese for their stimulating discussion and constructive criticism of this manuscript. This work was supported by grants from the National Institute for Deafness and Other Communication Disorders (grant numbers: R01DC010433, R43DC010084,

References (114)

  • A.V. Tzingounis et al.

    Arc/Arg3. 1: linking gene expression to synaptic plasticity and memory

    Neuron

    (2006)
  • L.H. Brennaman

    Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity

    Neurobiol. Dis.

    (2011)
  • M.G. Zhao

    Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory

    Neuron

    (2005)
  • J.W. Pilley et al.

    Border collie comprehends object names as verbal referents

    Behav. Processes

    (2011)
  • Y. Yotsumoto

    Different dynamics of performance and brain activation in the time course of perceptual learning

    Neuron

    (2008)
  • L. Ma

    Changes in regional activity are accompanied with changes in inter-regional connectivity during 4 weeks motor learning

    Brain Res.

    (2010)
  • K. Molina-Luna

    Motor learning transiently changes cortical somatotopy

    Neuroimage

    (2008)
  • H. Takahashi

    Learning-stage-dependent, field-specific, map plasticity in the rat auditory cortex during appetitive operant conditioning

    Neuroscience

    (2011)
  • A. Hernández

    Decoding a perceptual decision process across cortex

    Neuron

    (2010)
  • G.M. Hodgson

    Darwinian coevolution of organizations and the environment

    Ecol. Econ.

    (2010)
  • H.L. Read

    Functional architecture of auditory cortex

    Curr. Opin. Neurobiol.

    (2002)
  • F. Crick

    Neural edelmanism

    Trends Neurosci.

    (1989)
  • D. De Ridder et al.

    The Darwinian plasticity hypothesis for tinnitus and pain

    Prog. Brain Res.

    (2007)
  • J.S. Bakin et al.

    Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig

    Brain Res.

    (1990)
  • S. Atiani

    Task difficulty and performance induce diverse adaptive patterns in gain and shape of primary auditory cortical receptive fields

    Neuron

    (2009)
  • J. Wolfe

    Sparse and powerful cortical spikes

    Curr. Opin. Neurobiol.

    (2010)
  • P.R. Roelfsema

    Perceptual learning rules based on reinforcers and attention

    Trends Cogn. Sci.

    (2010)
  • J. Olesen et al.

    The burden of brain diseases in Europe

    Eur. J. Neurol.

    (2003)
  • A.R. Møller

    Neural Plasticity and Disorders of the Nervous System

    (2006)
  • A.M. Lozano

    Harnessing plasticity to reset dysfunctional neurons

    N. Engl. J. Med.

    (2011)
  • D.V. Buonomano et al.

    Cortical plasticity: from synapses to maps

    Annu. Rev. Neurosci.

    (1998)
  • H. Flor

    Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation

    Nature

    (1995)
  • W. Mühlnickel

    Reorganization of auditory cortex in tinnitus

    Proc. Natl. Acad. Sci. U.S.A.

    (1998)
  • D.R.M. Langers

    Tinnitus does not require macroscopic tonotopic map reorganization

    Front. Syst. Neurosci.

    (2012)
  • N.D. Engineer

    Reversing pathological neural activity using targeted plasticity

    Nature

    (2011)
  • J.S. Bakin et al.

    Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis

    Proc. Natl. Acad. Sci. U.S.A.

    (1996)
  • M.P. Kilgard et al.

    Cortical map reorganization enabled by nucleus basalis activity

    Science

    (1998)
  • A.C. Puckett

    Plasticity in the rat posterior auditory field following nucleus basalis stimulation

    J. Neurophysiol.

    (2007)
  • R. Moucha

    Background sounds contribute to spectrotemporal plasticity in primary auditory cortex

    Exp. Brain Res.

    (2005)
  • M.P. Kilgard

    Spectral features control temporal plasticity in auditory cortex

    Audiol. Neurootol.

    (2001)
  • M.P. Kilgard et al.

    Plasticity of temporal information processing in the primary auditory cortex

    Nat. Neurosci.

    (1998)
  • M.P. Kilgard

    Spectral features control temporal plasticity in auditory cortex

    Audiol. Neurootol.

    (2001)
  • R. Moucha et al.

    Cortical plasticity and rehabilitation

    Prog. Brain Res.

    (2006)
  • D. Hassert

    The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala

    Behav. Neurosci.

    (2004)
  • A.E. Dorr et al.

    Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission

    J. Pharmacol. Exp. Ther.

    (2006)
  • K.B. Clark

    Enhanced recognition memory following vagus nerve stimulation in human subjects

    Nat. Neurosci.

    (1999)
  • D.J. Englot

    Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response

    J. Neurosurg.

    (2011)
  • J.G. Turner

    Gap detection deficits in rats with tinnitus: a potential novel screening tool

    Behav. Neurosci.

    (2006)
  • J.A. Henry

    General review of tinnitus: prevalence, mechanisms, effects, and management

    J. Speech Lang. Hear. Res.

    (2005)
  • M.P. Kilgard

    Sensory input directs spatial and temporal plasticity in primary auditory cortex

    J. Neurophysiol.

    (2001)
  • Cited by (79)

    • Vagus nerve stimulation for tinnitus: A review and perspective

      2021, Progress in Brain Research
      Citation Excerpt :

      Yet, vagus nerve stimulation can also be paired with external stimuli, driving neuroplasticity by resetting dysfunctional circuits through cortical map expansion. This provides a form of replication with variation that supports a Darwinian mechanism to select the most behaviorally useful circuits (Kilgard, 2012). Vagus nerve stimulation can be clinically performed in 2 ways: non-invasively, i.e. non-surgically and invasively, i.e. surgically.

    • The tactile experience paired with vagus nerve stimulation determines the degree of sensory recovery after chronic nerve damage

      2021, Behavioural Brain Research
      Citation Excerpt :

      Depletion of acetylcholine in the cortex or temporally uncoupling of VNS and rehabilitation prevents enhancement of plasticity and subsequently precludes recovery of motor function, indicating that VNS-directed synaptic plasticity underlies motor recovery. In the context of sensory improvements, pairing VNS with auditory stimuli drives reorganization in auditory circuits that is associated with a reduction in tinnitus [34,36,55,58–60]. Similar mechanisms likely underlie the VNS-dependent enhancement of somatosensory recovery observed here.

    View all citing articles on Scopus
    View full text