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S66: TMS & drugs revisited 2014
Abstracts of Speakers / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339
S63 High frequency activity in the peri-ictal period J. Gotman Montreal Neurological Institute, Westmount, Canada High frequency oscillations (HFOs) have been studied particularly in the interictal period. Their location appears to be a good indicator of the epileptogenic zone in patients with focal epilepsy. Because of this relationship with epileptogenicity, it is of interest to know if they vary systematically in peri-ictal period, particularly prior to seizures. Experimental work in the pilocarpine model ofigh Frequency Activity in the h temporal lobe epilepsy, ripples and fast ripples appear to be specific preictal markers of different seizure types (hypersynchronous vs. low amplitude fast activity, Levesque et al, 2012). During pre-ictal periods in human patients, there seems to be a non-specific increase in ripples and fast ripples prior to seizure onset and after seizure onset. This is accompanied by a surprising increase in activity of the lower traditional frequency bands (Perucca et al, in press). It appears that there is a discrepancy between experimental and human data, and human seizures are often preceded by an increase in activity in all frequency bands, which may reflect a shift in the state of the brain different from a shift in the level of alertness. References: Levesque M, Salami P, Gotman J, Avoli M. Two Seizure Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy. J Neurosci 32:13264-13272, 2012. Perucca P, Dubeau F and Gotman J. Widespread EEG Changes Precede Focal Seizures, PLoS One, in press.
S64 Cortical control of the hand: movement generation and action observation R. Lemon, A. Kraskov UCL Institute of Neurology, Sobell Dept, London, United Kingdom The corticospinal tract is derived from multiple regions of the cerebral cortex and through its descending collaterals and terminations makes connections with multiple levels of the sensorimotor system, and exerts a wide degree of influence over different spinal circuits. Although all mammals possess a corticospinal tract, this system actually shows a remarkable degree of variation across species, which probably reflects the relative importance to those species of the different functions to which it can contribute. In primates, the corticospinal projections from the primary motor cortex have long been implicated in the generation of movement, and a large body of work has shown strong relationships between corticospinal discharge and various parameters of movement, such as the force and direction. It has also been possible to show direct causal effects of corticospinal activity on motor output, and to attribute these to direct cortico-motoneuronal (CM) projections to motoneurons of hand muscles. Recently it has been possible to extend these findings to show the involvement of CM projections in skilled tool use. Nevertheless, it is also clear that these direct CM projections do not work in isolation from other descending systems. It is also clear that although these systems can, to some extent, compensate for damage to the corticospinal projections, key features of skilled hand function are permanently lost. Interestingly, motor cortex can also be active during processes that do not require movement generation per se. These include mental rehearsal of motor acts and, intriguingly, observation of the actions of others. Recent work shows that even M1 corticospinal neurons are active during action observation, that is, they behave like “mirror neurons”. The study of the discharge of identified corticospinal neurons during action observation and during action execution by the monkey itself provides some clues as to what distinguishes the level of corticospinal activity normally associated with the generation of a voluntary movement. It also reveals the key role of suppression of corticospinal neuron activity during certain types of movement, observed and executed. Funding: The Wellcome Trust, UCL Grand Challenge Scheme.
S15
S65 Plasticity induced by non-invasive brain stimulation: review of recent progress W. Paulus Universitaet Goettingen, Goettingen, Germany Systematic non-invasive brain stimulation techniques date back to the beginning of the 19th century. The development of the voltaic pile led to first applications of DC stimulation with controlled current intensities in 1801, usually by listing series of treatments of individual patients. Since no controllable “biomarker” for a systematic evaluation of stimulation parameters was available most of these approaches were given up over time. TMS of the motor cortex allows for easy quantification of cortical excitability by measuring the motor evoked potential. Most of our “biomarker data” on transcranial stimulation effects rely on this technique. In addition MRI, EEG, PET and other techniques provide a conceptual framework which enables hypothesis guided brain stimulation for increasing or decreasing cortical functions and for treatment of patients. This talk will focus on recent progress in transcranial alternating and random noise stimulation techniques.
S66 TMS & drugs revisited 2014 U. Ziemann University of Tuebingen, Neurology, Tuebingen, Germany The combination of pharmacology and transcranial magnetic stimulation (pharmaco-TMS) has considerably improved our understanding of the effects of TMS on the human brain. This presentation will highlight important knowledge and recent advances in the contribution of pharmaco-TMS to the following fields: (1) Characterization of TMS measures of motor excitability (such as motor threshold, motor evoked potential amplitude, cortical silent period duration, paired-pulse measures of cortical inhibition and facilitation) by CNS active drugs with a specific mode of action; (2) characterization of the CNS effects of drugs with unknown modes of action by TMS measures of motor cortical excitability; (3) effects of CNS active drugs on TMS-induced plasticity; (4) TMS-induced changes in endogenous neurotransmitters and neuromodulators; (5) Effects of CNS active drugs on TMS measures of motor cortical excitability in neurological disease. The content of this lecture is a summary of highlights of a solicited review to be published in Clinical Neurophysiology in 2014.
S67 25 years of neuroimaging in amyotrophic lateral sclerosis M. Turner University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom History will judge the development of magnetic resonance imaging (MRI) as one of the major landmarks in neuroscience, bringing the post mortem neuropathological insights of Charcot and other pioneers to the in vivo routine clinical domain. While MRI retains an important role in the exclusion of alternative pathology in those suspected to have amyotrophic lateral sclerosis (ALS), advanced applications now provide a parallel role as a source of much-needed biomarkers. Neuroimaging more widely continues to provide important clues to pathogenic mechanisms in ALS, which is now firmly established as a multiple system cerebral disorder. With the increasing understanding of brain function in terms of networks, neuroimaging is currently the leading method to study ALS as a motor system, not just neuronal, degeneration. Developments in computational neuroscience and biostatistics mean that combined structural and functional cerebral connectivity can now be studied non-invasively, and this is being extended to the pre-symptomatic period through the study of those carrying genetic mutations linked to ALS. Meanwhile the potential of MRI at routine clinical scanner field strengths, to provide biomarkers sensitive enough in the context of a therapeutic trial is being tested through emerging international collaboration. MRI may ultimately be one part of a multimodal biomarker panel that includes biofluid and neurophysiological measurements.
S63 High frequency activity in the peri-ictal period J. Gotman Montreal Neurological Institute, Westmount, Canada High frequency oscillations (HFOs) have been studied particularly in the interictal period. Their location appears to be a good indicator of the epileptogenic zone in patients with focal epilepsy. Because of this relationship with epileptogenicity, it is of interest to know if they vary systematically in peri-ictal period, particularly prior to seizures. Experimental work in the pilocarpine model ofigh Frequency Activity in the h temporal lobe epilepsy, ripples and fast ripples appear to be specific preictal markers of different seizure types (hypersynchronous vs. low amplitude fast activity, Levesque et al, 2012). During pre-ictal periods in human patients, there seems to be a non-specific increase in ripples and fast ripples prior to seizure onset and after seizure onset. This is accompanied by a surprising increase in activity of the lower traditional frequency bands (Perucca et al, in press). It appears that there is a discrepancy between experimental and human data, and human seizures are often preceded by an increase in activity in all frequency bands, which may reflect a shift in the state of the brain different from a shift in the level of alertness. References: Levesque M, Salami P, Gotman J, Avoli M. Two Seizure Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy. J Neurosci 32:13264-13272, 2012. Perucca P, Dubeau F and Gotman J. Widespread EEG Changes Precede Focal Seizures, PLoS One, in press.
S64 Cortical control of the hand: movement generation and action observation R. Lemon, A. Kraskov UCL Institute of Neurology, Sobell Dept, London, United Kingdom The corticospinal tract is derived from multiple regions of the cerebral cortex and through its descending collaterals and terminations makes connections with multiple levels of the sensorimotor system, and exerts a wide degree of influence over different spinal circuits. Although all mammals possess a corticospinal tract, this system actually shows a remarkable degree of variation across species, which probably reflects the relative importance to those species of the different functions to which it can contribute. In primates, the corticospinal projections from the primary motor cortex have long been implicated in the generation of movement, and a large body of work has shown strong relationships between corticospinal discharge and various parameters of movement, such as the force and direction. It has also been possible to show direct causal effects of corticospinal activity on motor output, and to attribute these to direct cortico-motoneuronal (CM) projections to motoneurons of hand muscles. Recently it has been possible to extend these findings to show the involvement of CM projections in skilled tool use. Nevertheless, it is also clear that these direct CM projections do not work in isolation from other descending systems. It is also clear that although these systems can, to some extent, compensate for damage to the corticospinal projections, key features of skilled hand function are permanently lost. Interestingly, motor cortex can also be active during processes that do not require movement generation per se. These include mental rehearsal of motor acts and, intriguingly, observation of the actions of others. Recent work shows that even M1 corticospinal neurons are active during action observation, that is, they behave like “mirror neurons”. The study of the discharge of identified corticospinal neurons during action observation and during action execution by the monkey itself provides some clues as to what distinguishes the level of corticospinal activity normally associated with the generation of a voluntary movement. It also reveals the key role of suppression of corticospinal neuron activity during certain types of movement, observed and executed. Funding: The Wellcome Trust, UCL Grand Challenge Scheme.
S15
S65 Plasticity induced by non-invasive brain stimulation: review of recent progress W. Paulus Universitaet Goettingen, Goettingen, Germany Systematic non-invasive brain stimulation techniques date back to the beginning of the 19th century. The development of the voltaic pile led to first applications of DC stimulation with controlled current intensities in 1801, usually by listing series of treatments of individual patients. Since no controllable “biomarker” for a systematic evaluation of stimulation parameters was available most of these approaches were given up over time. TMS of the motor cortex allows for easy quantification of cortical excitability by measuring the motor evoked potential. Most of our “biomarker data” on transcranial stimulation effects rely on this technique. In addition MRI, EEG, PET and other techniques provide a conceptual framework which enables hypothesis guided brain stimulation for increasing or decreasing cortical functions and for treatment of patients. This talk will focus on recent progress in transcranial alternating and random noise stimulation techniques.
S66 TMS & drugs revisited 2014 U. Ziemann University of Tuebingen, Neurology, Tuebingen, Germany The combination of pharmacology and transcranial magnetic stimulation (pharmaco-TMS) has considerably improved our understanding of the effects of TMS on the human brain. This presentation will highlight important knowledge and recent advances in the contribution of pharmaco-TMS to the following fields: (1) Characterization of TMS measures of motor excitability (such as motor threshold, motor evoked potential amplitude, cortical silent period duration, paired-pulse measures of cortical inhibition and facilitation) by CNS active drugs with a specific mode of action; (2) characterization of the CNS effects of drugs with unknown modes of action by TMS measures of motor cortical excitability; (3) effects of CNS active drugs on TMS-induced plasticity; (4) TMS-induced changes in endogenous neurotransmitters and neuromodulators; (5) Effects of CNS active drugs on TMS measures of motor cortical excitability in neurological disease. The content of this lecture is a summary of highlights of a solicited review to be published in Clinical Neurophysiology in 2014.
S67 25 years of neuroimaging in amyotrophic lateral sclerosis M. Turner University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom History will judge the development of magnetic resonance imaging (MRI) as one of the major landmarks in neuroscience, bringing the post mortem neuropathological insights of Charcot and other pioneers to the in vivo routine clinical domain. While MRI retains an important role in the exclusion of alternative pathology in those suspected to have amyotrophic lateral sclerosis (ALS), advanced applications now provide a parallel role as a source of much-needed biomarkers. Neuroimaging more widely continues to provide important clues to pathogenic mechanisms in ALS, which is now firmly established as a multiple system cerebral disorder. With the increasing understanding of brain function in terms of networks, neuroimaging is currently the leading method to study ALS as a motor system, not just neuronal, degeneration. Developments in computational neuroscience and biostatistics mean that combined structural and functional cerebral connectivity can now be studied non-invasively, and this is being extended to the pre-symptomatic period through the study of those carrying genetic mutations linked to ALS. Meanwhile the potential of MRI at routine clinical scanner field strengths, to provide biomarkers sensitive enough in the context of a therapeutic trial is being tested through emerging international collaboration. MRI may ultimately be one part of a multimodal biomarker panel that includes biofluid and neurophysiological measurements.