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48. Preconditioning with low frequency rTMS over right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1
Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88
Introduction: Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands, and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a destabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e., high previous activity enhances the threshold for synaptic strengthening and vice versa. In accordance with, it has been shown for the human motor cortex electrophysiologically that excitability-enhancing stimulation with transcranial direct current stimulation (tDCS) caused a subsequent repetitive magnetic stimulation (rTMS) protocol to reduce excitability, while excitability-diminishing tDCS induced reversed effects. However, the relevance of metaplasticity for actual learning processes has not been tested so far. Methods: The experiments were carried out in 48 healthy young subjects. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, by transcranial direct current stimulation (only anodal or cathodal tDCS for each subgroup of subjects, each subgroup consisted of 24 persons). Anodal, cathodal or placebo tDCS were applied for 10 min. To enhance the efficacy of tDCS to induce motor cortex excitability alterations, d-cycloserine, a partial NMDA receptor-agonist, or placebo medication, was co-administered in a dosage of 100 mg. Results: Anodal and cathodal tDCS, if combined with d-cycloserine, impaired SRTT-performance. No other drug/placebo medicationtDCS combination influenced motor learning. Conclusion: Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has only a limited influence on implicit sequential motor learning. doi:10.1016/j.clinph.2008.07.048
48. Preconditioning with low frequency rTMS over right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1—P. Ragert, M. Camus, Y. Vandermeeren, L.G. Cohen (National Institutes of Health, HCPS, NINDS, Bethesda, USA) Introduction: Theta-Burst Stimulation (TBS) is a novel non-invasive method of conditioning the human motor cortex (M1) that can induce bidirectional changes in corticospinal excitability depending on the choice of stimulus parameters. However, several previous human studies provided evidence that the outcome of non-invasive brain stimulation depends on the previous history of neural activity. These findings indicate that homeostatic plasticity in human M1 might be one important physiological mechanism for the regulation of corticospinal excitability. While homeostatic plasticity has been demonstrated within M1 of one hemisphere, little is known to which extent it operates across the two hemispheres. Methods: Using two subsequent brain stimulation protocols, we sought to determine whether preconditioning of the right M1 by means of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) influences the effect of iTBS on corticospinal excitability over left M1. Subjects were randomly allocated to one of the four experimental groups in a sham-controlled parallel design. The only difference between each group was the type of the brain stimulation protocol (real/sham) applied to the right and left M1. In general, right M1 stimulation using 1 Hz rTMS or sham preceded left M1 stimulation (iTBS or sham) by approximately 10 minutes.
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Changes in corticospinal excitability of the ipsilateral (left) MI were assessed by recruitment curves (RCs) to TMS. Additionally, pinch force, simple reaction time and tapping speed were assessed in the right hand. Results: When applied alone, 1 Hz rTMS over right M1 and iTBS over left M1 increased RCs in the left M1 relative to sham. However, the effect of iTBS on RCs was diminished when the right M1 was preconditioned with 1 Hz rTMS. Motor performance of the right hand remained unchanged under all conditions. Significance: The present findings suggest that homeostatic mechanisms might contribute to regulate plasticity across human motor cortices. doi:10.1016/j.clinph.2008.07.049
50. Resting-state synchronisation in hepatic encephalopathy—M. Butz 1, J. Gross 2, L. Timmermann 3, T. Montez 4, B. Pollok 1, T. Kramer 5, G. Kircheis 5, D. Häussinger 5, A. Schnitzler 1 (1 HeinrichHeine-Universität, Neurologische Klinik, Düsseldorf, Germany, 2 University of Glasgow, Center for Cognitive Neuroimaging, Glasgow, UK, 3 Universität Köln, Klinik und Poliklinik für Neurologie, Köln, Germany, 4 VU Medical Center, Department of Clinical Neurophysiology and MEG Centre, Amsterdam, The Netherlands, 5 Heinrich-Heine-Universität, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Düsseldorf, Germany) Objective: Hepatic encephalopathy (HE) is a complication occurring within patients suffering from cirrhosis of the liver. HE is characterised by a variety of cognitive and motor deficits. Previous studies demonstrated that motor symptoms like mini-asterixis at high grade HE arise from a pathologically slowed drive of the primary motor cortex towards the muscles and the thalamus. Furthermore, higher HE-grades lead to a gradual reduction in the critical flicker frequency (CFF), a measure for perception of oscillatory visual stimuli. Thus, CFF appears to be a sensitive and reliable diagnostic tool for classification of HE. Synchronization Likelihood (SL) is a novel measure that can be used to quantify the integration of many brain regions by comparing the activity of each sensor with all other sensors. In this study, we hypothesised that worsening of HE – determined by CFF – goes along with global alterations in the oscillatory processing in the human brain as expressed by SL. Materials and methods: In 50 subjects, healthy controls and cirrhotic patients with no HE (HE 0; control patients), minimal HE (mHE) and manifest HE grades 1 and 2 (controls = 10, HE0 = 10; mHE = 10; HE1 = 10; HE2 = 10), spontaneous activity was recorded with a NeuromagTM-122 wholehead MEG-system for 3–5 min during a no-task eyes-closed condition. Additionally, individual CFF was assessed. Overall SL expressing the mean SL of all sensor combinations was calculated for an artifact-free period of 20 seconds for seven different frequency domains: 1–3, 4–7, 8–12, 12–20, 20–30, 30–45 and 1–45 Hz. Between-group comparison was done by an univariate ANOVA, and post-hoc test paired comparison (Bonferroni) was calculated. Finally, we calculated regression between CFF and SL in all frequency ranges and between CFF and age. Results: We could show that compared to healthy controls, SL is exclusively increased significantly in the 4–7 Hz range (theta) in patients suffering from manifest HE grades 1 and 2. For HE0 and mHE patients, a trend to a significant lower SL compared to HE2 patients could be observed. There was no significant difference in SL between controls, HE0 and mHE patients and between HE1 and HE2 patients. CFF and SL showed exclusively a significant regression in the theta range of 4–7 Hz suggesting that with increasing CFF, SL in the theta range decreases and vice versa.
Introduction: Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands, and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a destabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e., high previous activity enhances the threshold for synaptic strengthening and vice versa. In accordance with, it has been shown for the human motor cortex electrophysiologically that excitability-enhancing stimulation with transcranial direct current stimulation (tDCS) caused a subsequent repetitive magnetic stimulation (rTMS) protocol to reduce excitability, while excitability-diminishing tDCS induced reversed effects. However, the relevance of metaplasticity for actual learning processes has not been tested so far. Methods: The experiments were carried out in 48 healthy young subjects. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, by transcranial direct current stimulation (only anodal or cathodal tDCS for each subgroup of subjects, each subgroup consisted of 24 persons). Anodal, cathodal or placebo tDCS were applied for 10 min. To enhance the efficacy of tDCS to induce motor cortex excitability alterations, d-cycloserine, a partial NMDA receptor-agonist, or placebo medication, was co-administered in a dosage of 100 mg. Results: Anodal and cathodal tDCS, if combined with d-cycloserine, impaired SRTT-performance. No other drug/placebo medicationtDCS combination influenced motor learning. Conclusion: Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has only a limited influence on implicit sequential motor learning. doi:10.1016/j.clinph.2008.07.048
48. Preconditioning with low frequency rTMS over right motor cortex (M1) influences the effect of intermittent theta burst stimulation on excitability over left M1—P. Ragert, M. Camus, Y. Vandermeeren, L.G. Cohen (National Institutes of Health, HCPS, NINDS, Bethesda, USA) Introduction: Theta-Burst Stimulation (TBS) is a novel non-invasive method of conditioning the human motor cortex (M1) that can induce bidirectional changes in corticospinal excitability depending on the choice of stimulus parameters. However, several previous human studies provided evidence that the outcome of non-invasive brain stimulation depends on the previous history of neural activity. These findings indicate that homeostatic plasticity in human M1 might be one important physiological mechanism for the regulation of corticospinal excitability. While homeostatic plasticity has been demonstrated within M1 of one hemisphere, little is known to which extent it operates across the two hemispheres. Methods: Using two subsequent brain stimulation protocols, we sought to determine whether preconditioning of the right M1 by means of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) influences the effect of iTBS on corticospinal excitability over left M1. Subjects were randomly allocated to one of the four experimental groups in a sham-controlled parallel design. The only difference between each group was the type of the brain stimulation protocol (real/sham) applied to the right and left M1. In general, right M1 stimulation using 1 Hz rTMS or sham preceded left M1 stimulation (iTBS or sham) by approximately 10 minutes.
e23
Changes in corticospinal excitability of the ipsilateral (left) MI were assessed by recruitment curves (RCs) to TMS. Additionally, pinch force, simple reaction time and tapping speed were assessed in the right hand. Results: When applied alone, 1 Hz rTMS over right M1 and iTBS over left M1 increased RCs in the left M1 relative to sham. However, the effect of iTBS on RCs was diminished when the right M1 was preconditioned with 1 Hz rTMS. Motor performance of the right hand remained unchanged under all conditions. Significance: The present findings suggest that homeostatic mechanisms might contribute to regulate plasticity across human motor cortices. doi:10.1016/j.clinph.2008.07.049
50. Resting-state synchronisation in hepatic encephalopathy—M. Butz 1, J. Gross 2, L. Timmermann 3, T. Montez 4, B. Pollok 1, T. Kramer 5, G. Kircheis 5, D. Häussinger 5, A. Schnitzler 1 (1 HeinrichHeine-Universität, Neurologische Klinik, Düsseldorf, Germany, 2 University of Glasgow, Center for Cognitive Neuroimaging, Glasgow, UK, 3 Universität Köln, Klinik und Poliklinik für Neurologie, Köln, Germany, 4 VU Medical Center, Department of Clinical Neurophysiology and MEG Centre, Amsterdam, The Netherlands, 5 Heinrich-Heine-Universität, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Düsseldorf, Germany) Objective: Hepatic encephalopathy (HE) is a complication occurring within patients suffering from cirrhosis of the liver. HE is characterised by a variety of cognitive and motor deficits. Previous studies demonstrated that motor symptoms like mini-asterixis at high grade HE arise from a pathologically slowed drive of the primary motor cortex towards the muscles and the thalamus. Furthermore, higher HE-grades lead to a gradual reduction in the critical flicker frequency (CFF), a measure for perception of oscillatory visual stimuli. Thus, CFF appears to be a sensitive and reliable diagnostic tool for classification of HE. Synchronization Likelihood (SL) is a novel measure that can be used to quantify the integration of many brain regions by comparing the activity of each sensor with all other sensors. In this study, we hypothesised that worsening of HE – determined by CFF – goes along with global alterations in the oscillatory processing in the human brain as expressed by SL. Materials and methods: In 50 subjects, healthy controls and cirrhotic patients with no HE (HE 0; control patients), minimal HE (mHE) and manifest HE grades 1 and 2 (controls = 10, HE0 = 10; mHE = 10; HE1 = 10; HE2 = 10), spontaneous activity was recorded with a NeuromagTM-122 wholehead MEG-system for 3–5 min during a no-task eyes-closed condition. Additionally, individual CFF was assessed. Overall SL expressing the mean SL of all sensor combinations was calculated for an artifact-free period of 20 seconds for seven different frequency domains: 1–3, 4–7, 8–12, 12–20, 20–30, 30–45 and 1–45 Hz. Between-group comparison was done by an univariate ANOVA, and post-hoc test paired comparison (Bonferroni) was calculated. Finally, we calculated regression between CFF and SL in all frequency ranges and between CFF and age. Results: We could show that compared to healthy controls, SL is exclusively increased significantly in the 4–7 Hz range (theta) in patients suffering from manifest HE grades 1 and 2. For HE0 and mHE patients, a trend to a significant lower SL compared to HE2 patients could be observed. There was no significant difference in SL between controls, HE0 and mHE patients and between HE1 and HE2 patients. CFF and SL showed exclusively a significant regression in the theta range of 4–7 Hz suggesting that with increasing CFF, SL in the theta range decreases and vice versa.