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      Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs) Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP) Analysis in Patients with Major Depressive Disorder

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          Abstract

          Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram ( n = 32, 10.0 ± 4.0 mg/day), sertraline ( n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation ( n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders ( p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP ( p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group ( p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

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          A standardized boundary element method volume conductor model.

          We used a 3-compartment boundary element method (BEM) model from an averaged magnetic resonance image (MRI) data set (Montreal Neurological Institute) in order to provide simple access to realistically shaped volume conductor models for source reconstruction, as compared to individually derived models. The electrode positions were transformed into the model's coordinate system, and the best fit dipole results were transformed back to the original coordinate system. The localization accuracy of the new approach was tested in a comparison with simulated data and with individual BEM models of epileptic spike data from several patients. The standard BEM model consisted of a total of 4770 nodes, which describe the smoothed cortical envelope, the outside of the skull, and the outside of the skin. The electrode positions were transformed to the model coordinate system by using 3-5 fiducials (nasion, left and right preauricular points, vertex, and inion). The transformation consisted of an averaged scaling factor and a rigid transformation (translation and rotation). The potential values at the transformed electrode positions were calculated by linear interpolation from the stored transfer matrix of the outer BEM compartment triangle net. After source reconstruction the best fit dipole results were transformed back into the original coordinate system by applying the inverse of the first transformation matrix. Test-dipoles at random locations and with random orientations inside of a highly refined reference BEM model were used to simulate noise-free data. Source reconstruction results using a spherical and the standardized BEM volume conductor model were compared to the known dipole positions. Spherical head models resulted in mislocation errors at the base of the brain. The standardized BEM model was applied to averaged and unaveraged epileptic spike data from 7 patients. Source reconstruction results were compared to those achieved by 3 spherical shell models and individual BEM models derived from the individual MRI data sets. Similar errors to that evident with simulations were noted with spherical head models. Standardized and individualized BEM models were comparable. This new approach to head modeling performed significantly better than a simple spherical shell approximation, especially in basal brain areas, including the temporal lobe. By using a standardized head for the BEM setup, it offered an easier and faster access to realistically shaped volume conductor models as compared to deriving specific models from individual 3-dimensional MRI data.
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            The problem of functional localization in the human brain.

            Functional imaging gives us increasingly detailed information about the location of brain activity. To use this information, we need a clear conception of the meaning of location data. Here, we review methods for reporting location in functional imaging and discuss the problems that arise from the great variability in brain anatomy between individuals. These problems cause uncertainty in localization, which limits the effective resolution of functional imaging, especially for brain areas involved in higher cognitive function.
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              Intensity dependence of auditory evoked potentials as an indicator of central serotonergic neurotransmission: a new hypothesis.

              Because of the increasing importance of the central serotonergic neurotransmission for pathogenetic concepts and its role as a target of pharmacotherapeutic interventions in psychiatry, reliable indicators of this system are needed. It is proposed that the stimulus intensity dependence of auditory evoked N1/P2-component, which is probably modulated by cortical serotonergic innervation, may be a useful and noninvasive indicator of behaviorally relevant aspects of serotonergic activity. Converging evidence from our own studies as well as from the literature suggests that a pronounced intensity dependence of auditory evoked N1/P2-component reflects low central serotonergic neurotransmission. Recent findings concerning general functional aspects of the brain serotonin system reveal that this system is well qualified for adjusting individual levels of sensory processing ("set the tone"), especially in the primary auditory cortex in which the N1/P2-component is mainly generated. Dipole source analysis represents an important methodological advance in this context because it allows the separation of N1/P2-subcomponents generated in the primary auditory cortex from those generated in secondary auditory areas.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 March 2015
                March 2015
                : 16
                : 3
                : 6251-6265
                Affiliations
                [1 ]Department of Psychiatry, Seoul Eunpyeong Hospital, 90, Baengnyeonsan-ro, Eunpyeong-gu, Seoul 122-913, Korea; E-Mail: punzza91@ 123456naver.com
                [2 ]Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, 2240, Daehwa-dong, Ilsanseo-gu, Goyang 411-706, Korea; E-Mail: lshpss@ 123456hanmail.net
                [3 ]Clinical Emotion and Cognition Research Laboratory, Inje University, Goyang 411-706, Korea; E-Mail: miseon@ 123456bme.hanyang.ac.kr
                [4 ]Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Korea
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: medipark@ 123456hanmail.net ; Tel.: +82-31-910-7260; Fax: +82-31-910-7268.
                Article
                ijms-16-06251
                10.3390/ijms16036251
                4394530
                25794285
                1b62989d-2729-4879-8fad-2ca91b0928a3
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 December 2014
                : 12 March 2015
                Categories
                Article

                Molecular biology
                antidepressants,loudness dependence of auditory evoked potentials (ldaep),standardized low resolution brain electromagnetic tomography (sloreta),major depressive disorder,response,serotonin

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