Trends in Neurosciences
OpinionHarnessing plasticity to understand learning and treat disease
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)
- et al.
Central sensitization: a generator of pain hypersensitivity by central neural plasticity
J. Pain
(2009) Cortical map plasticity improves learning but is not necessary for improved performance
Neuron
(2011)Experience dependent plasticity alters cortical synchronization
Hear. Res.
(2007)Asynchronous inputs alter excitability, spike timing, and topography in primary auditory cortex
Hear. Res.
(2005)Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors
Neuroscience
(2011)Post-training unilateral vagal stimulation enhances retention performance in the rat
Neurobiol. Learn. Mem.
(1995)- et al.
The neuroscience of tinnitus
Trends Neurosci.
(2004) P50 gating deficit in Alzheimer dementia correlates to frontal neuropsychological function
Neurobiol. Aging
(2010)Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex
Exp. Neurol.
(2012)Lesions of the basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning
Neuron
(2003)
Arc/Arg3. 1: linking gene expression to synaptic plasticity and memory
Neuron
Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity
Neurobiol. Dis.
Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory
Neuron
Border collie comprehends object names as verbal referents
Behav. Processes
Different dynamics of performance and brain activation in the time course of perceptual learning
Neuron
Changes in regional activity are accompanied with changes in inter-regional connectivity during 4 weeks motor learning
Brain Res.
Motor learning transiently changes cortical somatotopy
Neuroimage
Learning-stage-dependent, field-specific, map plasticity in the rat auditory cortex during appetitive operant conditioning
Neuroscience
Decoding a perceptual decision process across cortex
Neuron
Darwinian coevolution of organizations and the environment
Ecol. Econ.
Functional architecture of auditory cortex
Curr. Opin. Neurobiol.
Neural edelmanism
Trends Neurosci.
The Darwinian plasticity hypothesis for tinnitus and pain
Prog. Brain Res.
Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig
Brain Res.
Task difficulty and performance induce diverse adaptive patterns in gain and shape of primary auditory cortical receptive fields
Neuron
Sparse and powerful cortical spikes
Curr. Opin. Neurobiol.
Perceptual learning rules based on reinforcers and attention
Trends Cogn. Sci.
The burden of brain diseases in Europe
Eur. J. Neurol.
Neural Plasticity and Disorders of the Nervous System
Harnessing plasticity to reset dysfunctional neurons
N. Engl. J. Med.
Cortical plasticity: from synapses to maps
Annu. Rev. Neurosci.
Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation
Nature
Reorganization of auditory cortex in tinnitus
Proc. Natl. Acad. Sci. U.S.A.
Tinnitus does not require macroscopic tonotopic map reorganization
Front. Syst. Neurosci.
Reversing pathological neural activity using targeted plasticity
Nature
Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis
Proc. Natl. Acad. Sci. U.S.A.
Cortical map reorganization enabled by nucleus basalis activity
Science
Plasticity in the rat posterior auditory field following nucleus basalis stimulation
J. Neurophysiol.
Background sounds contribute to spectrotemporal plasticity in primary auditory cortex
Exp. Brain Res.
Spectral features control temporal plasticity in auditory cortex
Audiol. Neurootol.
Plasticity of temporal information processing in the primary auditory cortex
Nat. Neurosci.
Spectral features control temporal plasticity in auditory cortex
Audiol. Neurootol.
Cortical plasticity and rehabilitation
Prog. Brain Res.
The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala
Behav. Neurosci.
Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission
J. Pharmacol. Exp. Ther.
Enhanced recognition memory following vagus nerve stimulation in human subjects
Nat. Neurosci.
Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response
J. Neurosurg.
Gap detection deficits in rats with tinnitus: a potential novel screening tool
Behav. Neurosci.
General review of tinnitus: prevalence, mechanisms, effects, and management
J. Speech Lang. Hear. Res.
Sensory input directs spatial and temporal plasticity in primary auditory cortex
J. Neurophysiol.
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2021, Progress in Brain ResearchCitation 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 ResearchCitation 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.