Cortical Plasticity

Congenital auditory deprivation (deafness) leads to a dysfunctional intrinsic cortical microcircuitry. This chapter reviews these deficits with a particular emphasis on layer-specific activity within the primary auditory cortex. Evidence for a delay in activation of supragranular layers and reduction in activity in infragranular layers is discussed. Such deficits indicate the incompetence of the primary auditory cortex to not only properly process thalamic input and generate output within the infragranular layers, but also incorporate top-down modulations from higher order auditory cortex into the processing within primary auditory cortex. Such deficits are the consequence of a misguided postnatal development. Maturation of primary auditory cortex in deaf animals shows evidence of a developmental delay and further alterations in gross synaptic currents, spread of activation, and morphology of local field potentials recorded at the cortical surface. Additionally, degenerative changes...

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Leber congenital amaurosis (LCA) is a rare hereditary retinal degeneration caused by mutations in more than a dozen genes. RPE65, one of these mutated genes, is highly expressed in the retinal pigment epithelium where it encodes the retinoid isomerase enzyme essential for the production of chromophore which forms the visual pigment in rod and cone photoreceptors of the retina. Congenital loss of chromophore production due to RPE65-deficiency together with progressive photoreceptor degeneration cause severe and progressive loss of vision. RPE65-associated LCA recently gained recognition outside of specialty ophthalmic circles due to early success achieved by three clinical trials of gene therapy using recombinant adeno-associated virus (AAV) vectors. The trials were built on multitude of basic, pre-clinical and clinical research defining the pathophysiology of the disease in human subjects and animal models, and demonstrating the proof-of-concept of gene (augmentation) therapy. Subst...

The cortical representation of the sensory environment is continuously modified by experience. Changes in spatial (receptive field) and temporal response properties of cortical neurons underlie many forms of natural learning. The scale and direction of these changes appear to be determined by specific features of the behavioral tasks that evoke cortical plasticity. The neural mechanisms responsible for this differential plasticity remain unclear partly because important sensory and cognitive parameters differ among these tasks. In this report, we demonstrate that differential sensory experience directs differential plasticity using a single paradigm that eliminates the task-specific variables that have confounded direct comparison of previous studies. Electrical activation of the basal forebrain (BF) was used to gate cortical plasticity mechanisms. The auditory stimulus paired with BF stimulation was systematically varied to determine how several basic features of the sensory input ...

There is increasing evidence that environmental and neuropharmacologic treatments enhance stroke recovery. Functional magnetic resonance imaging and transcranial magnetic stimulation have significantly broadened our understanding of the neuroanatomic relationships involved in recovery from brain injury due to stroke. These tools have also demonstrated the role for pharmacologic enhancement of cortical plasticity coupled with behavioral interventions. Robot-assisted therapy and partial body weight-supported treadmill gait training have demonstrated the role for technologic intervention in the modern neuro-rehabilitation setting. Current research using hemi-field ocular prisms and patching techniques suggest a role in the rehabilitation of hemianopsia and visual neglect. Finally, many advances have been made in the understanding of common stroke complications, such as depression, dysphagia, venous thromboembolic disease, incontinence, and spasticity.

Monocular deprivation experiments can be used to distinguish between different ideas concerning properties of cortical synaptic plasticity. Monocular deprivation by lid suture causes a rapid disconnection of the deprived eye connected to cortical neurons whereas total inactivation of the deprived eye produces much less of an ocular dominance shift. In order to understand these results one needs to know how lid suture and retinal inactivation affect neurons in the lateral geniculate nucleus (LGN) that provide the cortical input. Recent experimental results by Linden showed that monocular lid suture and monocular inactivation do not change the mean firing rates of LGN neurons but that lid suture reduces correlations between adjacent neurons whereas monocular inactivation leads to correlated firing. These, somewhat surprising, results contradict assumptions that have been made to explain the outcomes of different monocular deprivation protocols. Based on these experimental results we modify our assumptions about inputs to cortex during different deprivation protocols and show their implications when combined with different cortical plasticity rules. Using theoretical analysis, random matrix theory and simulations we show that high levels of correlations reduce the ocular dominance shift in learning rules that depend on homosynaptic depression (i.e., Bienenstock-Cooper-Munro type rules), consistent with experimental results, but have the opposite effect in rules that depend on heterosynaptic depression (i.e., Hebbian/principal component analysis type rules).

Somatosensory evoked potentials (SEP) to ipsilateral and contralateral median nerve stimulations were recorded from subdural electrode grids over the perirolandic areas in 41 patients with medically refractory focal epilepsies who underwent evaluation for epilepsy surgery. All patients showed clearly defined, high-amplitude contralateral median SEPs. In addition, four patients showed ipsilateral SEPs. Compared with the contralateral SEPs, ipsilateral SEPs were very localized, had a different spatial distribution, were of considerably lower amplitude, had a longer latency (1.2-17.8 ms), did not show an initial negativity, and were markedly attenuated during sleep. Stimulation of the subdural electrodes overlying the sensory hand area was associated with contralateral hand paresthesias, but no ipsilateral hand paresthesias, occurred. It was concluded that subdurally recorded cortical SEPs to ipsilateral stimulation of the median nerve (M) reflect unconscious sensory input from the han...

Intracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the effects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF affects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no effect on the normal developmental segregation of geniculocortical afferents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-...

Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease.

In this brief review, the body of work on hand use and cortical plasticity is reviewed. The hand movements and sensory inputs are represented in the mammalian primary motor cortex and the anterior parietal strip. The dominant organizational rules are that representational area is proportional to peripheral innervation, and that cortical architecture is columnar with limited horizontal spread. The representational area and columnar structure can be shaped by behavior and other input manipulations. The central core systems, and especially cholinergic inputs, act as teachers of the cerebral cortex by marking behavioral reinforcers with the release of acetylcholine. This marking is both necessary and sufficient for plasticity to occur in sensory cortex. As a result of this temporal marking of reinforcing events, nearly coincident inputs over restricted sensory, or motor, segments form coherent representations in primary sensory or motor cortex. Focal dystonia is a problem in which overuse of the hand leads to a lack of motor control, and especially inappropriate use of sensory feedback for motor control. Receptive field size, and columnar architecture, are highly abnormal in this disorder. The deficiencies in focal dystonia, and their appropriate treatment, can be understood by applying the principles of cortical plasticity to the behavioural manipulations that cause focal dystonia.