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S4-1 Surround inhibition in the human motor system
S14 assessed by threshold tracking. Investigating ionic mechanisms by monitoring the corresponding ionic currents is of clinical relevance, because once a specific ionic conductance is identified, pharmacologic blocking or modulation could provide a new therapeutic option. S3-4 Toxic and metabolic neuropathy M.C. Kiernan1 1 Neuroscience Research Australia and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia Following the validation of new testing protocols, clinical excitability techniques are now being adopted to complement diagnostic nerve conduction studies. Measurement of nerve excitability by threshold tracking provides complementary information to conventional nerve conduction studies and may be used to infer the activity of a variety of ion channels, energy-dependent pumps and ion exchange processes activated during the process of impulse conduction. While routine nerve conduction studies can document the presence of a neuropathy, they do not provide further insight into pathophysiology. A number of recent clinical excitability studies will be highlighted which have (i) established a mechanism for the neuropathy associated with renal failure; (ii) provided insight into the mechanisms of neurotoxicity associated with oxaliplatin chemotherapy; (iii) documented the acute effects of tetrodotoxininduced blockade of axonal Na+ channels in patients following pufferfish poisoning. There is now growing evidence to support the use of excitability studies to provide novel insights into the pathophysiological mechanisms involved in neuropathic disease states.
Oral Presentations: Symposia demonstrated in the human motor system, using transcranial magnetic stimulation (TMS) (Sohn and Hallett, 2004). Motor evoked potential (MEP) amplitude of the little finger muscle was significantly suppressed during voluntary flexion of the index finger, despite an increase in spinal excitability. This finding supports an idea that SI is an organizational principle of the human motor system. The functional operation of SI in the motor system is more efficient in the dominant hand than the nondominant hand (Shin et al, 2009). More efficient SI in the dominant hand could lead to greater dexterity in the dominant hand. The amount of SI is reduced in professional pianists compared to non-musician controls, and decreased after short-term exercise of finger movements. Reduced SI associated with long-term and short-term finger exercise suggests that overuse of hand muscles could induce alteration of SI operation. SI operation in the motor system is impaired in patients with focal hand dystonia (FHD) (Sohn and Hallett, 2004) and those with preclinical Parkinson disease (PD) (Shin et al, 2007), but is extended in patients with paroxysmal kinesigenic dyskinesia (PKD) during interictal periods (Shin et al, 2010). Impaired SI is a main physiological mechanism responsible for muscle co-contraction occurred in FHD, and for motor deficits in PD. Extended SI in PKD may represent a compensatory mechanism for preventing unwanted movements in surrounding muscles. S4-2 Mechanism of intracortical inhibition R. Hanajima1 Department of Neurology, Divisioin of Neuroscience, University of Tokyo, Tokyo, Japan 1
S4. Intracortical inhibition
Inhibitory mechanisms within the primary motor cortex (M1) are considered to have important roles to accomplish fine, coordinated finger movements. In animal experiments, electrical stimulation over the cortical surface produced inhibitory post-synaptic potentials in the neurons of the superficial layers. GABAergic inhibitory interneurons mainly mediate these intracortical inhibitions. In humans, we can evaluate the intracortical inhibitory circuits using paired transcranial magnetic stimulation (TMS) methods. In this talk, I summarize several inhibitory mechanisms within M1. Short interval intracortiical inhibition (SICI): When a subthreshold conditioning stimulus precedes the test TMS, motor evoked potentials (MEPs) are suppressed at iterstimulus intervals (ISIs) of 1 5 ms. Pharmacological studies indicate that this ipsilateral intracortical inhibition is mediated by GABAergic interneurons. Later corticospinal descending volleys elicited by TMS indirectly (I3waves) are affected by SICI. SICI for I3-waves continue up to 20 ms. This long duration of inhibition is also compatible with the duration of GABAA-mediated inhibition found in animal experiments. Long interval intracortical inhibtion (LICI): LICI is another inhibition induced by a conditioning TMS pulse set the same intensity as the test stimulus at ISIs of 100 150 ms. The later I-waves are affected by LICI. LICI is also generated in M1 and probably mediated by GABAB receptor. Interhemisperic inhibition (IHI): Inputs from the opposite M1 also induce its inhibition at ISIs around 10 ms. The IHI is generated through the corpus callosum. IHI also affects only later I-waves. Sensory afferent inhibition (SAI): Median nerve stimulation suppresses MEPs when TMS is given at 1 8 ms later than N20 latency of SEP. SAI is medicated by the thalamocortical inputs or the cortico-cortical inputs from the sensory cortex. Conclusion: The human hand motor area is regulated by these many kinds of inhibition from various parts, which enables M1 to execute fine, elegantly controlled hand movements.
S4-1 Surround inhibition in the human motor system
S4-3 Intracortical inhibition in movement disorders
Y.H. Sohn1 , H.-W. Shin2 , S.Y. Kang3 , M. Hallett4 1 Department of Neurology, Yonsei University College of Medicine, Seoul, Korea, 2 Department of Neurology, Chung-Ang University College of Medicine, Seoul, Korea, 3 Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, 4 Human Motor Control Section, NINDS, National Institutes of Health, Bethesda, Maryland, USA
R. Chen1 Divsion of Neurology, Department of Medicine, University of Toronto and Toronto Western Research Institute
S3-5 Hypothesis of conduction block in ALS H. Nodera1 Departmetn of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, USA
1
Amyotrophic lateral sclerosis (ALS) has been known to develop cellsize dependent heterogeneous motor neuron damage and motor axon loss. Therefore, nerve excitability may be different among motor axons with different threshold levels. Multiple nerve excitability tests were performed in 27 ALS patients and 23 control subjects with four different target threshold levels (10, 20, 40, and 60% of maximum compound muscle action potentials (CMAPs)). Compared to lower target levels, axons at high target levels in each group have the following characteristics: lower strength-duration time constant, less threshold reduction during depolarizing currents and greater threshold increase to hyperpolarizing currents. Furthermore, these linear amplitudedependent threshold relationships were not present in some of the ALS patients, demonstrating fanning-in (smaller threshold changes by long depolarizing and hyperpolarizing current) in threshold electrotonus (TE) at low target amplitude level. Longer distal latencies in median motor nerves were correlated with smaller threshold changes at low target amplitude level by long depolarizing or hyperpolarizing pulses. Taken together, peripheral motor axons in some ALS patients are characterized by increased variability of nerve excitability with significant membrane depolarization in low threshold axons. This may be associated with depolarizing conduction block and fasciculations.
Suppression of excitability in an area surrounding an activated neural network, also known as surround inhibition (SI), is a physiological mechanism that focuses neuronal activity and helps to selects only the appropriate neuronal response. SI is believed to be an essential mechanism in the motor system, where it can aid the selective execution of desired movements (Mink, 1996). Functional existence of SI has been
1
Intracortical inhibition can be tested with measurement of the silent period (SP) after single pulse transcranial magnetic stimulation (TMS) or with paired pulse TMS techniques. The SP is decreased in Parkinson’s disease (PD) and dystonia. Several studies found decreased short-interval intracortical inhibition (SICI) in PD and dystonia. However, this may be due to impaired inhibition or increased facilitation. The inhibition of SICI by long-interval intracortical inhibition (LICI), which may be a measure of presynaptic inhibition, is also reduced in PD. Cortical inhibition can also be evoked by activation of sensory afferents or stimulation of other cortical areas. Short latency afferent inhibition
Oral Presentations: Symposia demonstrated in the human motor system, using transcranial magnetic stimulation (TMS) (Sohn and Hallett, 2004). Motor evoked potential (MEP) amplitude of the little finger muscle was significantly suppressed during voluntary flexion of the index finger, despite an increase in spinal excitability. This finding supports an idea that SI is an organizational principle of the human motor system. The functional operation of SI in the motor system is more efficient in the dominant hand than the nondominant hand (Shin et al, 2009). More efficient SI in the dominant hand could lead to greater dexterity in the dominant hand. The amount of SI is reduced in professional pianists compared to non-musician controls, and decreased after short-term exercise of finger movements. Reduced SI associated with long-term and short-term finger exercise suggests that overuse of hand muscles could induce alteration of SI operation. SI operation in the motor system is impaired in patients with focal hand dystonia (FHD) (Sohn and Hallett, 2004) and those with preclinical Parkinson disease (PD) (Shin et al, 2007), but is extended in patients with paroxysmal kinesigenic dyskinesia (PKD) during interictal periods (Shin et al, 2010). Impaired SI is a main physiological mechanism responsible for muscle co-contraction occurred in FHD, and for motor deficits in PD. Extended SI in PKD may represent a compensatory mechanism for preventing unwanted movements in surrounding muscles. S4-2 Mechanism of intracortical inhibition R. Hanajima1 Department of Neurology, Divisioin of Neuroscience, University of Tokyo, Tokyo, Japan 1
S4. Intracortical inhibition
Inhibitory mechanisms within the primary motor cortex (M1) are considered to have important roles to accomplish fine, coordinated finger movements. In animal experiments, electrical stimulation over the cortical surface produced inhibitory post-synaptic potentials in the neurons of the superficial layers. GABAergic inhibitory interneurons mainly mediate these intracortical inhibitions. In humans, we can evaluate the intracortical inhibitory circuits using paired transcranial magnetic stimulation (TMS) methods. In this talk, I summarize several inhibitory mechanisms within M1. Short interval intracortiical inhibition (SICI): When a subthreshold conditioning stimulus precedes the test TMS, motor evoked potentials (MEPs) are suppressed at iterstimulus intervals (ISIs) of 1 5 ms. Pharmacological studies indicate that this ipsilateral intracortical inhibition is mediated by GABAergic interneurons. Later corticospinal descending volleys elicited by TMS indirectly (I3waves) are affected by SICI. SICI for I3-waves continue up to 20 ms. This long duration of inhibition is also compatible with the duration of GABAA-mediated inhibition found in animal experiments. Long interval intracortical inhibtion (LICI): LICI is another inhibition induced by a conditioning TMS pulse set the same intensity as the test stimulus at ISIs of 100 150 ms. The later I-waves are affected by LICI. LICI is also generated in M1 and probably mediated by GABAB receptor. Interhemisperic inhibition (IHI): Inputs from the opposite M1 also induce its inhibition at ISIs around 10 ms. The IHI is generated through the corpus callosum. IHI also affects only later I-waves. Sensory afferent inhibition (SAI): Median nerve stimulation suppresses MEPs when TMS is given at 1 8 ms later than N20 latency of SEP. SAI is medicated by the thalamocortical inputs or the cortico-cortical inputs from the sensory cortex. Conclusion: The human hand motor area is regulated by these many kinds of inhibition from various parts, which enables M1 to execute fine, elegantly controlled hand movements.
S4-1 Surround inhibition in the human motor system
S4-3 Intracortical inhibition in movement disorders
Y.H. Sohn1 , H.-W. Shin2 , S.Y. Kang3 , M. Hallett4 1 Department of Neurology, Yonsei University College of Medicine, Seoul, Korea, 2 Department of Neurology, Chung-Ang University College of Medicine, Seoul, Korea, 3 Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, 4 Human Motor Control Section, NINDS, National Institutes of Health, Bethesda, Maryland, USA
R. Chen1 Divsion of Neurology, Department of Medicine, University of Toronto and Toronto Western Research Institute
S3-5 Hypothesis of conduction block in ALS H. Nodera1 Departmetn of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, USA
1
Amyotrophic lateral sclerosis (ALS) has been known to develop cellsize dependent heterogeneous motor neuron damage and motor axon loss. Therefore, nerve excitability may be different among motor axons with different threshold levels. Multiple nerve excitability tests were performed in 27 ALS patients and 23 control subjects with four different target threshold levels (10, 20, 40, and 60% of maximum compound muscle action potentials (CMAPs)). Compared to lower target levels, axons at high target levels in each group have the following characteristics: lower strength-duration time constant, less threshold reduction during depolarizing currents and greater threshold increase to hyperpolarizing currents. Furthermore, these linear amplitudedependent threshold relationships were not present in some of the ALS patients, demonstrating fanning-in (smaller threshold changes by long depolarizing and hyperpolarizing current) in threshold electrotonus (TE) at low target amplitude level. Longer distal latencies in median motor nerves were correlated with smaller threshold changes at low target amplitude level by long depolarizing or hyperpolarizing pulses. Taken together, peripheral motor axons in some ALS patients are characterized by increased variability of nerve excitability with significant membrane depolarization in low threshold axons. This may be associated with depolarizing conduction block and fasciculations.
Suppression of excitability in an area surrounding an activated neural network, also known as surround inhibition (SI), is a physiological mechanism that focuses neuronal activity and helps to selects only the appropriate neuronal response. SI is believed to be an essential mechanism in the motor system, where it can aid the selective execution of desired movements (Mink, 1996). Functional existence of SI has been
1
Intracortical inhibition can be tested with measurement of the silent period (SP) after single pulse transcranial magnetic stimulation (TMS) or with paired pulse TMS techniques. The SP is decreased in Parkinson’s disease (PD) and dystonia. Several studies found decreased short-interval intracortical inhibition (SICI) in PD and dystonia. However, this may be due to impaired inhibition or increased facilitation. The inhibition of SICI by long-interval intracortical inhibition (LICI), which may be a measure of presynaptic inhibition, is also reduced in PD. Cortical inhibition can also be evoked by activation of sensory afferents or stimulation of other cortical areas. Short latency afferent inhibition