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S5-2 Pharmacological modulation of HFOs
29th International Congress of Clinical Neurophysiology (SAI) and long latency afferent inhibition (LAI) elicited by median nerve stimulation followed by TMS of the motor cortex are reduced in PD. Cerebellar stimulation reduces cortical excitability through the cerebello-thalamocortical pathway and cerebellar inhibition of the motor cortex is reduced in PD patients off medications. Interhemispheric inhibition is impaired focal dystonia and in PD patients with mirror movements. Studies of cortical inhibition can be used to assess the effects of treatment. In PD, dopaminergic medications restored deficient SICI but had no effect on reduced LAI and presynpatic inhibition, and may cause reduced SAI. Deep brain stimulation of the subthalamic nucleus restored deficient SICI, SAI and LAI whereas deep brain stimulation of the internal globus pallidus increased the SP. In dystonia, SICI may be restored after botulinum toxin injections. The abnormalities in cortical inhibition are not specific to any particular disease and may be due to the disease processes or compensatory mechanisms. Measures of cortical inhibition are to useful ways to study the pathophysiology of movement disorders and to understand the effects of different treatments. S4-4 Transcranial brain stimulation and cortical plasticity V. Di Lazzaro1 1 Department od Neuroscience, Universit` a Cattolica Repetitive transcranial magnetic stimulation (rTMS) of the human brain can produce long-lasting changes in the excitability of the motor cortex. rTMS may increase or decrease motor cortical excitability depending critically on the characteristics of the stimulation protocol. The effects of rTMS are often described as LTD- or LTP-like, because they seem to implicate changes in synaptic strength. The hypothesis that rTMS may produce LTP and LTD like effects is supported by the strong correlation between several features of the effects of rTMS and the key features of synaptic plasticity: effects outlasting the period of stimulation, critical role of the frequency of stimulation and the number of stimuli delivered, influence of prior activation of neuronal networks, interaction with learning and memory, influence of genetic background. Insight into the physiological basis of the after effects of rTMS has also been provided by direct recordings of the corticospinal volleys evoked by single pulse TMS from the epidural space of conscious patients with chronically implanted spinal electrodes. These studies confirmed that the main changes produced by rTMS take place at the cortical level. Moreover, they provided several new findings: rTMS does not simply disrupt the ongoing activity of the cerebral cortex but modulates the excitability of specific circuits of the human brain; as observed using paired pulse stimulation protocols, the cortical circuits generating the I1- and late I-waves can be selectively modulated; rTMS can enhance the excitability of circuits independent from those generating the late I-waves, thus suggesting that there are segregated structures of the human cerebral cortex that can be modulated independently using rTMS; though the changes produced by facilitatory and inhibitory rTMS protocols as evaluated with motor evoked potentials recording are apparently similar, the effects may involve different structures within the central motor circuits. S5. High frequency oscillations (HFOs) S5-1 Exploring the physiology and function of high-frequency oscillations (HFOs) from the somatosensory cortex I. Hashimoto1 Kanazawa Institute of Technology, Tokyo, Japan
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Among a wide spectrum of cortical oscillatory activities, a rhythm with a much higher frequency (HFOs, 300 900 Hz) was first recorded electrically and then magnetically from the somatosensory cortex after stimulation of the median nerve. Curio et al. (1994) were the first to record HFOs magnetically and speculated that HFOs are of heterogeneous origins with contributions from presynaptic action potentials as well as postsynaptic potentials of different populations of cortical neurons. In support of the speculation above, a dissociated behavior for the early and late HFOs has been demonstrated. An earliest part of HFOs may reflect presynaptic action potentials of the thalamocortical fibers. However, for the remaining part of the HFOs, it is still in a rudimentary stage for understanding its physiology and function. In view of an inevitable biological jitter in the chemical transmission of the central nervous system, it is surprising that averaged and summated
S15 activity of SI has such a high-frequency signal. It is generally assumed that slow oscillations involve large brain areas, whereas fast oscillations, small areas; the size of activated neuronal pool is inversely related to their frequency. For example, slow rhythms are generated by medium to long range neural networks such as thalamo-cortical circuits and corticocortical networks. In contrast, fast rhythms may be produced by an extremely small area such as intracortical micro-circuits consisting of excitatory and inhibitory neurons. Fast coupling of the excitatory and inhibitory activities in the microcircuits can bring about submillisecond precision of spike timing. Thus, these intracortical micro-circuits can be a substrate for generating HFOs. In addition, recent work suggests the role of electrotonic coupling by gap-junction in promoting the synchronous firing of local networks in the cortex. S5-2 Pharmacological modulation of HFOs D. Restuccia1 1 Department of Neurosciences, Catholic University, Rome, Italy Since the early article of Moruzzi and Magoun (1949), it is generally agreed that the arousal system influence not only the cortical activation, but also the sensory-motor responsiveness and activity. Looking at the somatosensory input, such an influence is not reflected by relevant modifications of standard SEPs, which remain substantially unchanged during sleep or arousal; by contrast, 600 Hz High Frequency Oscillations (HFOs), evoked by upper limb stimulation and superimposed to the primary N20, are diminished during sleep and increased during eyes opening. These findings suggest that HFOs reflect the influence of the arousal system on the somatosensory input processing. Since neuronal aggregates that form the arousal system act on other CNS structures by means of several neurotransmitters, such as glutamate, GABA, norepinephrine, dopamine, a simple way to test the effects of these structures on HFOs is the analysis of their modifications after administration of drugs modulating the dynamics of the abovementioned transmitters. Until now, several studies examined HFO modifications after single-dose administration of different drugs: modafinil (Della Marca et al., 2004), propofol (Klostermann et al., 2000), rivastigmine, an inhibitor of central acetylcholinesterase (Restuccia et al., 2003), different GABAergic drugs (lorazepam, acting on GABAA receptors; Restuccia et al., 2002, and tiagabine, acting on GABAB receptors, Restuccia et al., 2002). All these studies, regardless their actual action on HFOs, revealed that drugs can act on HFOs generation at different levels of the central nervous system. Here, we aimed at summarize this consistent body of data and its impact on our current knowledge about the HFOs generation mechanisms. S5-3 HFOs in amyotrophic lateral sclerosis (ALS) M. Hamada1 , Y. Ugawa2 1 Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2 Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima, Japan Several reports showed some interactions between the motor and sensory systems in humans. The integrations of the sensorimotor information might be necessary for precise and purposeful movements. In ALS, cortical reorganization within motor related areas has been shown by means of functional neuroimaging methods. This is considered to be some sort of partial compensation to optimize motor performances. However, in ALS, such compensation has not been well documented in other cortical regions. Thus, we hypothesize that similar compensation for motor dysfunction might occur in the somatosensory system in ALS. To investigate sensory cortical changes, we studied somatosensory evoked potentials (SEPs) and their high-frequency oscillation potentials in ALS. Subjects were 15 healthy volunteers and 26 ALS patients. Median nerve SEPs were recorded and several peaks of oscillations were obtained by digitally filtering raw SEPs. The patients were sorted into three groups according to the level of weakness of abductor pollicis brevis muscle (APB): mild, moderate and severe. The latencies and amplitudes of main and oscillation components of SEP were compared among normal subjects and the three patient groups. The early cortical response was enlarged in the moderate weakness group, while it was attenuated in the severe weakness group. No differences were noted in the size ratios of oscillations to the main SEP component between the patients and normal
1
Among a wide spectrum of cortical oscillatory activities, a rhythm with a much higher frequency (HFOs, 300 900 Hz) was first recorded electrically and then magnetically from the somatosensory cortex after stimulation of the median nerve. Curio et al. (1994) were the first to record HFOs magnetically and speculated that HFOs are of heterogeneous origins with contributions from presynaptic action potentials as well as postsynaptic potentials of different populations of cortical neurons. In support of the speculation above, a dissociated behavior for the early and late HFOs has been demonstrated. An earliest part of HFOs may reflect presynaptic action potentials of the thalamocortical fibers. However, for the remaining part of the HFOs, it is still in a rudimentary stage for understanding its physiology and function. In view of an inevitable biological jitter in the chemical transmission of the central nervous system, it is surprising that averaged and summated
S15 activity of SI has such a high-frequency signal. It is generally assumed that slow oscillations involve large brain areas, whereas fast oscillations, small areas; the size of activated neuronal pool is inversely related to their frequency. For example, slow rhythms are generated by medium to long range neural networks such as thalamo-cortical circuits and corticocortical networks. In contrast, fast rhythms may be produced by an extremely small area such as intracortical micro-circuits consisting of excitatory and inhibitory neurons. Fast coupling of the excitatory and inhibitory activities in the microcircuits can bring about submillisecond precision of spike timing. Thus, these intracortical micro-circuits can be a substrate for generating HFOs. In addition, recent work suggests the role of electrotonic coupling by gap-junction in promoting the synchronous firing of local networks in the cortex. S5-2 Pharmacological modulation of HFOs D. Restuccia1 1 Department of Neurosciences, Catholic University, Rome, Italy Since the early article of Moruzzi and Magoun (1949), it is generally agreed that the arousal system influence not only the cortical activation, but also the sensory-motor responsiveness and activity. Looking at the somatosensory input, such an influence is not reflected by relevant modifications of standard SEPs, which remain substantially unchanged during sleep or arousal; by contrast, 600 Hz High Frequency Oscillations (HFOs), evoked by upper limb stimulation and superimposed to the primary N20, are diminished during sleep and increased during eyes opening. These findings suggest that HFOs reflect the influence of the arousal system on the somatosensory input processing. Since neuronal aggregates that form the arousal system act on other CNS structures by means of several neurotransmitters, such as glutamate, GABA, norepinephrine, dopamine, a simple way to test the effects of these structures on HFOs is the analysis of their modifications after administration of drugs modulating the dynamics of the abovementioned transmitters. Until now, several studies examined HFO modifications after single-dose administration of different drugs: modafinil (Della Marca et al., 2004), propofol (Klostermann et al., 2000), rivastigmine, an inhibitor of central acetylcholinesterase (Restuccia et al., 2003), different GABAergic drugs (lorazepam, acting on GABAA receptors; Restuccia et al., 2002, and tiagabine, acting on GABAB receptors, Restuccia et al., 2002). All these studies, regardless their actual action on HFOs, revealed that drugs can act on HFOs generation at different levels of the central nervous system. Here, we aimed at summarize this consistent body of data and its impact on our current knowledge about the HFOs generation mechanisms. S5-3 HFOs in amyotrophic lateral sclerosis (ALS) M. Hamada1 , Y. Ugawa2 1 Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2 Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima, Japan Several reports showed some interactions between the motor and sensory systems in humans. The integrations of the sensorimotor information might be necessary for precise and purposeful movements. In ALS, cortical reorganization within motor related areas has been shown by means of functional neuroimaging methods. This is considered to be some sort of partial compensation to optimize motor performances. However, in ALS, such compensation has not been well documented in other cortical regions. Thus, we hypothesize that similar compensation for motor dysfunction might occur in the somatosensory system in ALS. To investigate sensory cortical changes, we studied somatosensory evoked potentials (SEPs) and their high-frequency oscillation potentials in ALS. Subjects were 15 healthy volunteers and 26 ALS patients. Median nerve SEPs were recorded and several peaks of oscillations were obtained by digitally filtering raw SEPs. The patients were sorted into three groups according to the level of weakness of abductor pollicis brevis muscle (APB): mild, moderate and severe. The latencies and amplitudes of main and oscillation components of SEP were compared among normal subjects and the three patient groups. The early cortical response was enlarged in the moderate weakness group, while it was attenuated in the severe weakness group. No differences were noted in the size ratios of oscillations to the main SEP component between the patients and normal