Cortical excitability and post-stroke recovery

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Biochemical Society Transactions (Impact Factor: 3.19). 12/2009; 37(Pt 6):1412-4. DOI: 10.1042/BST0371412
Source: PubMed


Stroke is the leading cause of adult disability. Recent studies show that the brain can engage in a limited process of neural repair after stroke: re-mapping of sensory and motor function and sprouting of new connections in peri-infarct cortex surrounding the stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. The central cellular process in these events is alteration in neuronal response to incoming inputs--manipulations that increase neuronal firing to a given input are likely to induce changes in neuronal structure and alterations in cortical maps. Because post-stroke neural repair and recovery also involves neuronal sprouting and re-mapping of cortical sensory and motor representations, it has been assumed that changes in neuronal excitability underlie neural repair.

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    • "Changes in neuronal excitability, loss of GABAergic inhibition , enhanced glutamatergic transmission, and synaptic plasticity all contribute to neuronal reorganization after stroke. Studies that promote an increase in local brain excitability result in improved function [21, 34, 39, 45] and suggest that decreasing GABA activity within the brain could facilitate structural changes that promote functional recovery [21] [34] [45]. In particular, this enhancement of neuronal excitability involves dampening baseline levels of inhibition. "
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    ABSTRACT: An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of lasting adult disability. Stroke-induced cell death occurs due to an excess release of glutamate. As a consequence to this, a compensatory increased release of GABA occurs that results in the subsequent internalization of synaptic GABA(A) receptors and spillover onto perisynaptic GABA(A) receptors, resulting in increased tonic inhibition. Recent studies show that the brain can engage in a limited process of neural repair after stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. It has been assumed that changes in neuronal excitability underlie processes of neural repair and remapping of cortical sensory and motor representations. Indeed, recent evidence suggests that local inhibitory and excitatory currents are altered after stroke and modulation of these networks to enhance excitability during the repair phase can facilitate functional recovery after stroke. More specifically, dampening tonic GABA inhibition can afford an early and robust improvement in functional recovery after stroke.
    Advances in Pharmacological Sciences 02/2012; 2012(2):708428. DOI:10.1155/2012/708428
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    • "In the present experiments, increasing TMS stimulation intensity by 10% produced changes that were reliably detected by the DI. This finding suggests that calculating the DI on repeated TMS/hd-EEG sessions may be effective in revealing rather fine modifications in cortical excitability (indexed by the response's amplitude) due to pathological alterations, i.e. stroke, epilepsy and depression [49]–[52] or therapeutic interventions, i.e. electroconvulsive therapy, rTMS, neurorehabilitation or drug administration [51], [52]. "
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    ABSTRACT: High-density electroencephalography (hd-EEG) combined with transcranial magnetic stimulation (TMS) provides a direct and non-invasive measure of cortical excitability and connectivity in humans and may be employed to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. However, the diagnostic/monitoring applications of this technique would be limited to the extent that TMS-evoked potentials are either stereotypical (non-sensitive) or random (non-repeatable) responses. Here, we used controlled changes in the stimulation parameters (site, intensity, and angle of stimulation) and repeated longitudinal measurements (same day and one week apart) to evaluate the sensitivity and repeatability of TMS/hd-EEG potentials. In 10 volunteers, we performed 92 single-subject comparisons to evaluate the similarities/differences between pairs of TMS-evoked potentials recorded in the same/different stimulation conditions. For each pairwise comparison, we used non-parametric statistics to calculate a Divergence Index (DI), i.e., the percentage of samples that differed significantly, considering all scalp locations and the entire post-stimulus period. A receiver operating characteristic analysis showed that it was possible to find an optimal DI threshold of 1.67%, yielding 96.7% overall accuracy of TMS/hd-EEG in detecting whether a change in the perturbation parameters occurred or not. These results demonstrate that the EEG responses to TMS essentially reflect deterministic properties of the stimulated neuronal circuits as opposed to stereotypical responses or uncontrolled variability. To the extent that TMS-evoked potentials are sensitive to changes and repeatable over time, they may be employed to detect longitudinal changes in the state of cortical circuits.
    PLoS ONE 04/2010; 5(4):e10281. DOI:10.1371/journal.pone.0010281 · 3.23 Impact Factor
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    ABSTRACT: Glutamate and GABA (gamma-aminobutyric acid) are the predominant excitatory and inhibitory neurotransmitters in the mammalian CNS (central nervous system) respectively, and as such have undergone intense investigation. Given their predominance, it is no wonder that the reciprocal receptors for these neurotransmitters have attracted so much attention as potential targets for the promotion of health and the treatment of disease. Indeed, dysfunction of these receptors underlies a number of well-characterized neuropathological conditions such as anxiety, epilepsy and neurodegenerative diseases. Although intrinsically linked, the glutamatergic and GABAergic systems have, by and large, been investigated independently, with researchers falling into the 'excitatory' or 'inhibitory' camps. Around 70 delegates gathered at the University of St Andrews for this Biochemical Society Focused Meeting aimed at bringing excitation and inhibition together. With sessions on behaviour, receptor structure and function, receptor trafficking, activity-dependent changes in gene expression and excitation/inhibition in disease, the meeting was the ideal occasion for delegates from both backgrounds to interact. This issue of Biochemical Society Transactions contains papers written by those who gave oral presentations at the meeting. In this brief introductory review, I put into context and give a brief overview of these contributions.
    Biochemical Society Transactions 12/2009; 37(Pt 6):1317-22. DOI:10.1042/BST0371317 · 3.19 Impact Factor
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