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P 187. Tinnitus-related neuroplastic alterations in the motor cortex
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
References Keitel C, Schröger E, Saupe K, Müller MM. Sustained selective intermodal attention modulates processing of language-like stimuli. Exp Brain Res 2011;213:321–7. Müller MM, Malinowski P, Gruber T, Hillyard SA. Sustained division of the attentional spotlight. Nature 2003;424:309–12. Saupe K, Schröger E, Andersen SK, Müller MM. Neural mechanisms of intermodal sustained selective attention with concurrently presented auditory and visual stimuli. Front Hum Neurosci 2009;3:58. doi:10.1016/j.clinph.2013.04.263
P 187. Tinnitus-related neuroplastic alterations in the motor cortex—M. Schecklmann a, E. Frank a, T. Kleinjung b, M. Landgrebe c, B. Langguth a (a University of Regensburg, Department of Psychiatry, Regensburg, Germany, b University of Zurich, Department of Otorhinolaryngology, Zurich, Switzerland, c Social Foundation Bamberg, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Bamberg, Germany) Introduction: Chronic tinnitus is a brain network disorder with involvement of auditory and non-auditory areas motivating the clinical use of repetitive transcranial magnetic stimulation (rTMS). Several small studies indicated that motor cortex excitability is altered in tinnitus. Furthermore, motor cortex excitability was changed according to treatment response of rTMS of auditory cortex. Objectives: Here, we aimed to investigate motor cortex excitability before and after rTMS of auditory cortex. Materials and methods: We investigated 231 patients with chronic tinnitus and 120 healthy controls in a retrospective manner pooling data from different studies. Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). 118 patients were tested twice-at the first and last day of treatment with temporal oriented rTMS. Treatment response was defined as fivepoint change in tinnitus questionnaire. Results: Tinnitus was associated with increased motor inhibition (SICI, CSP) and facilitation (ICF). Successful treatment response was associated with normalisation of increased SICI. Conclusion: Our data suggest that altered SICI may reflect a state parameter, whereas CSP and ICF may rather mirror a trait-like predisposing factor of tinnitus. doi:10.1016/j.clinph.2013.04.264
P 188. Pharmacological characterization of TMS-evoked EEG responses by positive modulators at the GABA-A receptor—I. Premoli a, D. Rivolta b, N. Perales Castellanos c, C. Zipser a, T. Heidegger a, F. Müller-Dalhlhaus a, U. Ziemann d,e (a Goethe University, Department of Neurology, Frankfurt, Germany, b Max Planck Institute for Brain Research, Department of Neurophysiology, Frankfurt, Germany, c Universidad Politécnica de Madrid, Centre for Biomedical Technology, Madrid, Spain, d EberhardKarls-University Tübingen, Department of Neurology and Stroke, Tuebingen, Germany, e Hertie Institute for Clinical Brain Research, Tuebingen, Germany) Introduction: The combined use of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) enables a direct investigation of cortical-evoked responses in humans. The physiology of the peaks characterizing the TMS-evoked EEG responses has not been clearly elucidated yet. EEG is able to detect fast-inhibitory post synaptic potentials (fIPSPs, <50 ms), which are linked to GABA-A receptor activity. Thus, the early TMS-evoked potentials (TEPs) could be generated and/or mediated by GABA-A receptors.
e153
Objectives: In the present study we characterized the pharmacophysiology of TEPs in healthy volunteers by using two GABA-A receptors positive modulators: alprazolam and zolpidem. The main aim of the study was to test to which extent early TEPs are affected by fast inhibitory neurotransmission through the GABA-A receptor. Materials and methods: Twenty healthy subjects participated in a pseudorandomized, placebo-controlled, double-blind crossover design, using a single oral dose of alprazolam (1 mg), a classical benzodiazepine preferentially binding on alpha1, alpha2, alpha3 and alpha5 subunit bearing subtypes of the GABA-A receptor, and zolpidem (10 mg), which mainly binds at the alpha1 subtype. TEPs were recorded by TMS-EEG before and 90 min after drug administration and the effects of the drugs on the TEP amplitudes were statistically evaluated. Results: A non parametric cluster-based permutation analysis of amplitudes at channel-level was run for placebo, alprazolam and zolpidem administration. Both alprazolam and zolpidem, increased the amplitude of the negative potential at 45 ms after stimulation (N45). Moreover, a strong positive correlation was found between their modulation on the N45 magnitude. In addition, alprazolam but not zolpidem decreased the amplitudes of the later TEPs, in particular, the negative at 100 ms (N100) and the positive at 180 ms (P180). Conclusion: We provide first-time evidence that the N45 potential may reflect a biological marker of alpha1 containing GABA-A receptor activity. The broader modulation of several TEP components by alprazolam could be explained by its wider pharmacological profile, as it is responsible for the activation of several subtypes of GABA-A receptors. doi:10.1016/j.clinph.2013.04.265
P 189. The extent of perifocal edema in function associated motor fibers correlates to the primary motor deficit in patients with M1adjacent intracerebral tumors. A volumetric analysis of presurgically acquired data based on MRI, FET-PET and navigated TMS on primary motor functions—V. Neuschmelting a, A. Eisenbeis a, C. Grefkes b,c, K.-J. Langen d, R. Goldbrunner a, W. Carolin a,b (a University Hospital Cologne, Department of Neurosurgery, Cologne, Germany, b Max-Planck-Institute for Neurological Research, Cologne, Germany, c University Hospital Cologne, Department of Neurology, Cologne, Germany, d Research Center Jülich, Institute of Neuroscience and Medicine, Jülich, Germany) Question: Many patients with brain tumors adjacent to the primary motor (M1) region initially present with transient or permanent motor deficits. Factors like compression by tumor mass, tumor infiltration, as well as the extent of the perifocal edema might contribute to the motor deficit. In order to assess the relevance of these factors, we analyzed the spatial relationship between M1 cortical representation assessed with navigated transcranial magnetic stimulation (nTMS) and the anatomical and metabolic extension of tumors in the M1 region in patients prior to surgery. Methods: To date, 21 patients with M1-adjacent tumors (glioblastoma (n = 14), anaplastic astrocytoma (n = 1), carcinoma metastasis (n = 4), anaplastic ependymoma (n = 1), lymphoma (n = 1)) underwent an anatomical MRI protocol including a T2-weighted sequence, a gadolinium-contrast-enhanced sequence (GCE) and diffused tensor imaging as well as 18F-fluoroethyl-L-tyrosine (FET) PET for presurgical planning. Cortical M1 representations for the hand, foot and tongue were assessed by nTMS within 7 days. “Functional” fiber tracking of the corticospinal tract (CST) consisted of the following processing steps: (1) setting the seed points defined by the coordinate revealing the highest motor evoked potential (MEP) when stim-
References Keitel C, Schröger E, Saupe K, Müller MM. Sustained selective intermodal attention modulates processing of language-like stimuli. Exp Brain Res 2011;213:321–7. Müller MM, Malinowski P, Gruber T, Hillyard SA. Sustained division of the attentional spotlight. Nature 2003;424:309–12. Saupe K, Schröger E, Andersen SK, Müller MM. Neural mechanisms of intermodal sustained selective attention with concurrently presented auditory and visual stimuli. Front Hum Neurosci 2009;3:58. doi:10.1016/j.clinph.2013.04.263
P 187. Tinnitus-related neuroplastic alterations in the motor cortex—M. Schecklmann a, E. Frank a, T. Kleinjung b, M. Landgrebe c, B. Langguth a (a University of Regensburg, Department of Psychiatry, Regensburg, Germany, b University of Zurich, Department of Otorhinolaryngology, Zurich, Switzerland, c Social Foundation Bamberg, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Bamberg, Germany) Introduction: Chronic tinnitus is a brain network disorder with involvement of auditory and non-auditory areas motivating the clinical use of repetitive transcranial magnetic stimulation (rTMS). Several small studies indicated that motor cortex excitability is altered in tinnitus. Furthermore, motor cortex excitability was changed according to treatment response of rTMS of auditory cortex. Objectives: Here, we aimed to investigate motor cortex excitability before and after rTMS of auditory cortex. Materials and methods: We investigated 231 patients with chronic tinnitus and 120 healthy controls in a retrospective manner pooling data from different studies. Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). 118 patients were tested twice-at the first and last day of treatment with temporal oriented rTMS. Treatment response was defined as fivepoint change in tinnitus questionnaire. Results: Tinnitus was associated with increased motor inhibition (SICI, CSP) and facilitation (ICF). Successful treatment response was associated with normalisation of increased SICI. Conclusion: Our data suggest that altered SICI may reflect a state parameter, whereas CSP and ICF may rather mirror a trait-like predisposing factor of tinnitus. doi:10.1016/j.clinph.2013.04.264
P 188. Pharmacological characterization of TMS-evoked EEG responses by positive modulators at the GABA-A receptor—I. Premoli a, D. Rivolta b, N. Perales Castellanos c, C. Zipser a, T. Heidegger a, F. Müller-Dalhlhaus a, U. Ziemann d,e (a Goethe University, Department of Neurology, Frankfurt, Germany, b Max Planck Institute for Brain Research, Department of Neurophysiology, Frankfurt, Germany, c Universidad Politécnica de Madrid, Centre for Biomedical Technology, Madrid, Spain, d EberhardKarls-University Tübingen, Department of Neurology and Stroke, Tuebingen, Germany, e Hertie Institute for Clinical Brain Research, Tuebingen, Germany) Introduction: The combined use of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) enables a direct investigation of cortical-evoked responses in humans. The physiology of the peaks characterizing the TMS-evoked EEG responses has not been clearly elucidated yet. EEG is able to detect fast-inhibitory post synaptic potentials (fIPSPs, <50 ms), which are linked to GABA-A receptor activity. Thus, the early TMS-evoked potentials (TEPs) could be generated and/or mediated by GABA-A receptors.
e153
Objectives: In the present study we characterized the pharmacophysiology of TEPs in healthy volunteers by using two GABA-A receptors positive modulators: alprazolam and zolpidem. The main aim of the study was to test to which extent early TEPs are affected by fast inhibitory neurotransmission through the GABA-A receptor. Materials and methods: Twenty healthy subjects participated in a pseudorandomized, placebo-controlled, double-blind crossover design, using a single oral dose of alprazolam (1 mg), a classical benzodiazepine preferentially binding on alpha1, alpha2, alpha3 and alpha5 subunit bearing subtypes of the GABA-A receptor, and zolpidem (10 mg), which mainly binds at the alpha1 subtype. TEPs were recorded by TMS-EEG before and 90 min after drug administration and the effects of the drugs on the TEP amplitudes were statistically evaluated. Results: A non parametric cluster-based permutation analysis of amplitudes at channel-level was run for placebo, alprazolam and zolpidem administration. Both alprazolam and zolpidem, increased the amplitude of the negative potential at 45 ms after stimulation (N45). Moreover, a strong positive correlation was found between their modulation on the N45 magnitude. In addition, alprazolam but not zolpidem decreased the amplitudes of the later TEPs, in particular, the negative at 100 ms (N100) and the positive at 180 ms (P180). Conclusion: We provide first-time evidence that the N45 potential may reflect a biological marker of alpha1 containing GABA-A receptor activity. The broader modulation of several TEP components by alprazolam could be explained by its wider pharmacological profile, as it is responsible for the activation of several subtypes of GABA-A receptors. doi:10.1016/j.clinph.2013.04.265
P 189. The extent of perifocal edema in function associated motor fibers correlates to the primary motor deficit in patients with M1adjacent intracerebral tumors. A volumetric analysis of presurgically acquired data based on MRI, FET-PET and navigated TMS on primary motor functions—V. Neuschmelting a, A. Eisenbeis a, C. Grefkes b,c, K.-J. Langen d, R. Goldbrunner a, W. Carolin a,b (a University Hospital Cologne, Department of Neurosurgery, Cologne, Germany, b Max-Planck-Institute for Neurological Research, Cologne, Germany, c University Hospital Cologne, Department of Neurology, Cologne, Germany, d Research Center Jülich, Institute of Neuroscience and Medicine, Jülich, Germany) Question: Many patients with brain tumors adjacent to the primary motor (M1) region initially present with transient or permanent motor deficits. Factors like compression by tumor mass, tumor infiltration, as well as the extent of the perifocal edema might contribute to the motor deficit. In order to assess the relevance of these factors, we analyzed the spatial relationship between M1 cortical representation assessed with navigated transcranial magnetic stimulation (nTMS) and the anatomical and metabolic extension of tumors in the M1 region in patients prior to surgery. Methods: To date, 21 patients with M1-adjacent tumors (glioblastoma (n = 14), anaplastic astrocytoma (n = 1), carcinoma metastasis (n = 4), anaplastic ependymoma (n = 1), lymphoma (n = 1)) underwent an anatomical MRI protocol including a T2-weighted sequence, a gadolinium-contrast-enhanced sequence (GCE) and diffused tensor imaging as well as 18F-fluoroethyl-L-tyrosine (FET) PET for presurgical planning. Cortical M1 representations for the hand, foot and tongue were assessed by nTMS within 7 days. “Functional” fiber tracking of the corticospinal tract (CST) consisted of the following processing steps: (1) setting the seed points defined by the coordinate revealing the highest motor evoked potential (MEP) when stim-