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      Developmental aspects of cortical excitability and inhibition in depressed and healthy youth: an exploratory study

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          Abstract

          Objectives: The objective of this post-hoc exploratory analysis was to examine the relationship between age and measures of cortical excitability and inhibition.

          Methods: Forty-six participants (24 with major depressive disorder and 22 healthy controls) completed MT, SICI, ICF, and CSP testing in a cross-sectional protocol. Of these 46 participants, 33 completed LICI testing. Multiple linear robust regression and Spearman partial correlation coefficient were used to examine the relationship between age and the TMS measures.

          Results: In the overall sample of 46 participants, age had a significant negative relationship with motor threshold (MT) in both the right ( r s = −0.49, adjusted p = 0.007; β = −0.08, adjusted p = 0.001) and left ( r s = −0.42, adjusted p = 0.029; β = −0.05, adjusted p = 0.004) hemispheres. This significant negative relationship of age with MT was also observed in the sample of depressed youth in both the right ( r s = −0.70, adjusted p = 0.002; β = −0.09, adjusted p = 0.001) and left ( r s = −0.54, adjusted p = 0.034; β = −0.05, adjusted p = 0.017) hemispheres, but not in healthy controls. In the sample of the 33 participants who completed LICI testing, age had a significant negative relationship with LICI (200 ms interval) in both the right ( r s = −0.48, adjusted p = 0.05; β = −0.24, adjusted p = 0.007) and left ( r s = −0.64, adjusted p = 0.002; β = −0.23, adjusted p = 0.001) hemispheres. This negative relationship between age and LICI (200 ms interval) was also observed in depressed youth in both the right ( r s = −0.76, adjusted p = 0.034; β = −0.35, adjusted p = 0.004) and left ( r s = −0.92, adjusted p = 0.002; β = −0.25, adjusted p = 0.001) hemispheres.

          Conclusion: These findings suggest that younger children have higher MTs. This is more pronounced in depressed youth than healthy controls. LICI inhibition may also increase with age in youth.

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          Most cited references 47

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          On the cellular and network bases of epileptic seizures.

          The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear as a transformation of otherwise normal brain rhythms. The cerebral cortex and hippocampus are particularly prone to the generation of the large, synchronized bursts of activity underlying many forms of seizures owing to strong recurrent excitatory connections, the presence of intrinsically burst-generating neurons, ephaptic interactions among closely spaced neurons, and synaptic plasticity. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike-wave activity, again mediated both by intrinsic membrane properties and synaptic interactions. The interaction of the cerebral cortex and the thalamus, in conjunction with intrathalamic communication, can also generate spike waves similar to those occurring during human absence seizure discharges. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic "runaway" excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances.
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            Noninvasive brain stimulation: from physiology to network dynamics and back.

            Noninvasive brain stimulation techniques have been widely used for studying the physiology of the CNS, identifying the functional role of specific brain structures and, more recently, exploring large-scale network dynamics. Here we review key findings that contribute to our understanding of the mechanisms underlying the physiological and behavioral effects of these techniques. We highlight recent innovations using noninvasive stimulation to investigate global brain network dynamics and organization. New combinations of these techniques, in conjunction with neuroimaging, will further advance the utility of their application.
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              The role of GABA(B) receptors in intracortical inhibition in the human motor cortex.

              While GABA(B) receptors are thought to have an important role in mediating long interval intracortical inhibition (LICI) in the human motor cortex, the effect of a selective GABA(B) receptor agonist on this measure has not been directly tested. Nine healthy volunteers ingested either 50 mg baclofen (BAC) or placebo (PBO) in a randomized, double blind crossover design, with the second session one week later. We used transcranial magnetic stimulation to assess motor threshold, motor evoked potential (MEP) amplitude, cortical silent period (CSP) duration, short interval intracortical inhibition (SICI) and LICI before and 90 min following drug intake. There was no specific effect of drug on motor threshold, MEP amplitude or CSP duration. BAC resulted in a significant increase in LICI (P=0.002) and a significant decrease in SICI (P=0.046) while PBO had no effect. Our findings demonstrate that the enhanced GABA(B) receptor activation results in differential effects on these two measures of intracortical inhibition in the human motor cortex. The increase in LICI is likely to be a result of increased GABA(B) receptor mediated inhibitory post-synaptic potentials, while the reduction in SICI may relate to the activation of pre-synaptic GABA(B) receptors reducing GABA release.
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                Author and article information

                Contributors
                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                02 September 2014
                2014
                : 8
                Affiliations
                1Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic Rochester, MN, USA
                2Division of Biostatistics, Department of Clinical Sciences, UT Southwestern Medical Center Dallas, TX, USA
                3Department of Psychiatry, UT Southwestern Medical Center Dallas, TX, USA
                4Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, NC, USA
                5Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto Toronto, ON, Canada
                Author notes

                Edited by: Lindsay M. Oberman, E.P. Bradley Hospital and Warren Alpert Medical School of Brown University, USA

                Reviewed by: Sudha Kilaru Kessler, University of Pennsylvania School of Medicine, USA; Motoaki Nakamura, Kanagawa Psychiatric Center, Japan

                *Correspondence: Paul E. Croarkin, Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Generose, Rochester, MN 55905, USA e-mail: croarkin.paul@ 123456mayo.edu

                This article was submitted to the journal Frontiers in Human Neuroscience.

                Article
                10.3389/fnhum.2014.00669
                4151107
                Copyright © 2014 Croarkin, Nakonezny, Lewis, Zaccariello, Huxsahl, Husain, Kennard, Emslie and Daskalakis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 55, Pages: 9, Words: 7242
                Categories
                Neuroscience
                Original Research Article

                Neurosciences

                adolescents, depression, neurodevelopment, csp, icf, sici, lici, tms

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